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Dig Dis Sci. 2011 Feb 19. [Epub ahead of print]
Paul J. Gaglio1, 2 Contact Information, Noah Moss1, Camille McGaw1 and John Reinus1
(1) Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA
(2) Montefiore Einstein Liver Center, 111 East 210 Street, Bronx, NY 10467, USA
Contact Information Paul J. Gaglio
Email: pgaglio@montefiore.org
"In summary, the responses to this Internet-based survey of more than 1,000 current HCV treaters indicated that although the majority of respondents appear ready to utilize DAA agents in the future, referrals to "hepatitis C experts" will increase when these agents become available. In addition, future referrals to ID specialists appear to be limited. Finally, as more than half of respondents to the survey with "minimal knowledge" of DAA therapies also appear to be willing to utilize these compounds in the future, significant provider education will be required to minimize inappropriate use of these agents."
"Although a significant percentage of respondents who participated in clinical trials with a DAA (90%) or who were "aware or very aware" of these agents but did not participate in a clinical trial (81%) would use these agents in the future, more than half of respondents (52%) who reported minimal knowledge of DAA agents stated that they would also use them in the future. Although providers with minimal knowledge of DAA agents represented a small percentage of respondents to the survey, concern exists regarding the inappropriate use of DAAs in the future including inexperience with side-effect management, and lack of recognition of both treatment failure as well as the emergence of viral resistance [11-16]. It is therefore apparent to the authors of this manuscript that extensive education of all future prescribers of DAA agents will be required to ensure successful use of these therapies."
"Of respondents with "minimal knowledge" of DAA, 52% stated that they would use them in the future......Overall, a significant number of respondents who treat HCV today with currently available therapies indicated that they would not prescribe DAA therapies when they became available; 85% of respondents to the survey would evaluate and treat an HCV-infected patient "today" versus 81% when DAA agents became available (p = 0.0054). Similarly, more respondents indicated that they would refer their patients to a "hepatitis C specialist" after DAA agents became available (6% current, 10% after DAA availability (p = 0.016)...........A greater percentage of AGA members (12%) stated that they would refer their patient to an "HCV expert" when DAA agents became available compared to AASLD members (3%) (p = 0.001). When analyzing attitudes related to current and future therapy of HCV based on focus of clinical practice, a comparison of Hepatologists/liver transplantation physicians to Gastroenterologists revealed that 93% versus 86% would treat their HCV-infected patient today (p = 0.0034), 48% compared to 8% participated in clinical trials using DAA agents (p = 0.001), 90% versus 81% would treat their patient with a DAA agent (p = 0.001), and 1% versus 8% would refer their patient to an "HCV expert" when DAA therapies became available (p = 0.001). Practice type was also associated with differences in attitudes related to current and future therapy of HCV. Comparison of respondents in private practice versus those who practiced at a medical school or hospital associated with a medical school revealed that respectively, 91% versus 81% would treat their HCV-infected patient today (p = 0.001), 9% versus 30% participated in a clinical trial with a DAA agent (p = 0.001), 89% versus 75% would use DAA therapies when they became available (p = 0.001), and 12% compared to 15% would refer to an "HCV expert" when DAA therapies became available (P = NS). Current awareness and participation in clinical trials with DAA agents influenced attitudes regarding future use of these therapies, as 90% of respondents who participated in clinical trials with DAAs, 81% of those who were "very aware" or "aware" of DAA agents but did not participate in clinical trials, and 59% of those with minimal knowledge of DAA therapies would prescribe these agents in the future (p = 0.0001 clinical trial participant/very aware or aware of DAA agents vs. minimal knowledge). Respondents with "minimal knowledge" of DAA agents also reported that when these compounds were available in the future, 25% would refer their HCV-infected patient to a PA, NP, or other MD in their practice, 22% would refer to an "HCV expert," and 1% would refer to an ID specialist. Respondents who reported "minimal knowledge of DAA agents" were more likely to consider the AMA their primary professional organization (20 vs. 1% AGA/AASLD (p = 0.001)), or be in a private practice not associated with a medical school (83 vs. 17% practice or hospital associated with a medical school p = 0.0001)."
Introduction
Response to current therapy of hepatitis C virus (HCV) is suboptimal. Direct-acting antiviral therapies (DAA) are expected to improve treatment outcomes. Additional treatments for HCV will invariably make therapeutic choices and patient management more complex. We hypothesize that current perceptions regarding the complexity of DAA therapy will influence attitudes towards future use by practitioners who are currently treating HCV.
Methods
An Internet-based survey was sent to 10,082 AASLD and AGA members to determine if they treat HCV infection, their knowledge of DAA therapies, attitudes towards current and future HCV treatments, and if they participated in clinical trials using DAA agents.
Results
Out of a total of 1,757 individuals responding to the survey, 75% treat HCV; 79% were MDs, 67% were Gastroenterologists, and 24% were Hepatologists. Of the respondents, 77% indicated they were "very aware" or "aware" of DAA therapies, 20% participated in clinical trials, and 3% had minimal knowledge of DAA agents. Comparing treatment "today" versus in the future when DAAs were available, 85 vs. 81% would treat (p = 0.0054), 6 vs. 10% would refer to an "HCV expert" (p = 0.016), and 1% would refer to an ID specialist. Of respondents with "minimal knowledge" of DAA, 52% stated that they would use them in the future.
Conclusions
Although the majority of respondents appear ready to utilize DAA agents in the future, referrals to "hepatitis C experts" will increase. More than half of respondents with "minimal knowledge" of DAA therapies also appear to be willing to utilize these compounds, raising concerns regarding their inappropriate use. Broad education of healthcare providers to prevent inappropriate use of these agents will be critical.
Disclaimer: The statements, findings, conclusions, views, and opinions contained and expressed in this manuscript are based in part on data obtained under license from the following IMS Health Incorporated information service(s): Prescriber ProfilerÂȘ (2008-2009) IMS Health Incorporated. All Rights Reserved. The statements, findings, conclusions, views, and opinions contained and expressed herein are not necessarily those of IMS Health Incorporated or any of its affiliated or subsidiary entities. IMS Health had no role in the design and conduct of the study, collection, management, analysis, or interpretation of the data, and preparation or approval of this manuscript.
Introduction
Hepatitis C virus (HCV) represents the most common chronic blood-borne viral infection in the United States [1, 2]. At present, response to currently available therapy remains suboptimal as a significant number of patients fail to achieve a sustained virologic response to therapy [3-10]. Recent discoveries related to the life cycle and pathobiology of HCV have led to the development of novel therapies that directly inhibit viral replication. These compounds, characterized as "specifically targeted antiviral therapies against HCV" (STAT-C) or "direct-acting antiviral agents" (DAA) have been investigated in naive as well as previously treated patients, and preliminary data from these studies have been encouraging [11-14]. Along with these encouraging results, these and other publications which describe experience with DAA agents have documented the emergence of HCV resistance [15, 16], as well as significant treatment-related adverse events including rash, gastrointestinal side-effects, and anemia [11-14].
As health care providers with interest and experience in treating HCV become aware of emerging data using novel therapeutic agents, we hypothesize that current perceptions regarding the complexity and side-effects of DAA therapies will influence decisions regarding the future use of these agents. To evaluate attitudes regarding the future use of these agents by individuals who are currently treating HCV, we sent an Internet-based survey to all United States-based members of the American Gastroenterology Association (AGA) and American Association for the Study of Liver Disease (AASLD). Members of these societies were chosen because they represent both the vast majority of HCV treaters in the United States, and a population of clinicians likely to have knowledge of DAA therapies. Recipients of the survey were queried regarding their primary professional affiliation and focus of practice, attitudes towards current and future HCV therapy, as well as participation in clinical trials using DAA agents. We determined if any of these parameters affected attitudes related to current and future treatment decisions regarding HCV.
Methods
This study was reviewed and approved by the institutional review board at the Albert Einstein College of Medicine/Montefiore Medical Center. The e-mail addresses of the 10,082 US-based members of the AGA and AASLD were compiled from the 2009 member directories for both organizations. AGA and AASLD members were selected to be surveyed as they represent the majority of HCV treaters in the United States. Prescriber ProfilerTM data provided to the authors by IMS Health Incorporated, reflecting a US-based database of retail pharmacies and total dispensed prescriptions of CopegusTM, Intron-ATM, InfergenTM, PegasysTM, Peg-IntronTM, RebetolTM, RebetronTM, RibasphereTM, and RibavirinTM indicated that between December 2008 and November 2009, 177,300 prescriptions were written. Gastroenterologists or Hepatologists wrote approximately 94,000 or 55% of these, validating our hypothesis that the targeted survey recipients were a group which treated HCV most frequently. Internal medicine physicians (11%) and nurse practitioners (8%) were the next most common prescribers [17]. Using an Internet-based survey engine ("SurveyMonkey" (surveymonkey.com)) a nine-question survey was sent to each AGA or AASLD member; only one questionnaire was sent to individuals who are members of both organizations. If an individual did not respond to the survey, the survey was re-sent with a second request to complete the survey. All results were tabulated, and statistical analysis was performed using Stata version 9.2, Statcorp LP, College Station, Texas.
Results
Of the 10,082 surveys sent, 8,449 were deliverable. The most common reasons for inability to deliver a survey included use of an e-mail filter or vacation message by the intended recipient. A total 1,757 individuals responded to the survey, representing a 21% response rate. A recent analysis performed by supersurvey.com revealed a mean response rate of 18% to online surveys of similar question size and target audience (www.supersurvey.com). The survey questions and responses appear in Table 1. If a respondent stated that they did not treat HCV, their participation in the survey ended after question 1.
Of the respondents, 75% (1,320) stated that they treat HCV, and of these respondents, 79% were MDs, 10% were physician assistants or nurse practitioners, 8% MD-PhDs, 2% DO, and 1% PhD. Of the respondents, 32% graduated within the last 10 years, 25% 11-20 years ago, 21% 21-30 years ago, and 12% greater than 30 years ago.
When analyzing results based on focus of practice, 67% of respondents stated that gastroenterology was the primary focus of their clinical practice, 24% selected hepatology and/or liver transplantation, 2% infectious disease, and 7% stated "other" as the primary focus of their practice. The "other" respondents included primary care doctors, surgeons, as well as Gastroenterologists who considered hepato-biliary disease, oncology, or pancreatic disease their primary specialty. Forty-six percent of the respondents were in a private practice not associated with a medical school, 42% at a medical school or hospital associated with a medical school, 8% in a private practice associated with a medical school, and the remaining 4% of respondents practiced in a multispecialty group practice, Veterans Administration hospital, or hospital not associated with a medical school.
Professional affiliations were assessed; 55% of respondents considered the American Gastroenterological Association (AGA) their primary professional affiliation, 26% the American Association for the Study of Liver Disease (AASLD), 9% the American Society for Gastrointestinal Endoscopy (ASGE), and 10% "other" including the American College of Gastroenterology (ACG), American Medical Association (AMA), and the American Society for Transplantation (AST).
When queried regarding what they would do when presented with an HCV-infected patient "today," 85% of the respondents would treat them, 6% would refer them to a "hepatitis C expert," 4% would refer them to a physician extender (PA, NP, or specially trained nurse) in their practice, 4% would refer to another MD in their practice, and 1% would refer them to an infectious disease specialist. Related to future therapies for HCV including DAAs in combination with interferon and ribavirin, 77% of the respondents were "aware" or "very aware" of this concept but had not participated in any clinical trials using DAA agents, 20% were "very aware" and had experience using these agents in clinical trials, and 3% had "minimal knowledge" of DAA agents.
When queried regarding treatment approaches if a DAA agent were available "today," 81% of respondents would evaluate and treat the patient, 10% would refer the patient to a "hepatitis C expert," 5% would refer the patient to another physician in their group, and 4% would refer the patient to a physician extender (PA, NP, or specially trained nurse) in their practice. Less than 1% of respondents reported that they would refer the patient to an infectious disease specialist.
Analysis of survey results (Table 2....
Overall, a significant number of respondents who treat HCV today with currently available therapies indicated that they would not prescribe DAA therapies when they became available; 85% of respondents to the survey would evaluate and treat an HCV-infected patient "today" versus 81% when DAA agents became available (p = 0.0054). Similarly, more respondents indicated that they would refer their patients to a "hepatitis C specialist" after DAA agents became available (6% current, 10% after DAA availability (p = 0.016).
Significant differences existed based on primary professional affiliation in attitudes and experience of survey respondents related to present and future HCV therapy. Ninety-one percent of respondents who considered the AASLD their primary affiliation compared to 84% of AGA members would treat their HCV-infected patient today (p = 0.002), 48% of AASLD members versus 9% of AGA members participated in clinical trials with a DAA agent (p = 0001), and 91% of AASLD members versus 79% of AGA members would use a DAA agent to treat their HCV-infected patient in the future (p = 0.001). A greater percentage of AGA members (12%) stated that they would refer their patient to an "HCV expert" when DAA agents became available compared to AASLD members (3%) (p = 0.001). When analyzing attitudes related to current and future therapy of HCV based on focus of clinical practice, a comparison of Hepatologists/liver transplantation physicians to Gastroenterologists revealed that 93% versus 86% would treat their HCV-infected patient today (p = 0.0034), 48% compared to 8% participated in clinical trials using DAA agents (p = 0.001), 90% versus 81% would treat their patient with a DAA agent (p = 0.001), and 1% versus 8% would refer their patient to an "HCV expert" when DAA therapies became available (p = 0.001).
Practice type was also associated with differences in attitudes related to current and future therapy of HCV. Comparison of respondents in private practice versus those who practiced at a medical school or hospital associated with a medical school revealed that respectively, 91% versus 81% would treat their HCV-infected patient today (p = 0.001), 9% versus 30% participated in a clinical trial with a DAA agent (p = 0.001), 89% versus 75% would use DAA therapies when they became available (p = 0.001), and 12% compared to 15% would refer to an "HCV expert" when DAA therapies became available (P = NS).
Current awareness and participation in clinical trials with DAA agents influenced attitudes regarding future use of these therapies, as 90% of respondents who participated in clinical trials with DAAs, 81% of those who were "very aware" or "aware" of DAA agents but did not participate in clinical trials, and 59% of those with minimal knowledge of DAA therapies would prescribe these agents in the future (p = 0.0001 clinical trial participant/very aware or aware of DAA agents vs. minimal knowledge). Respondents with "minimal knowledge" of DAA agents also reported that when these compounds were available in the future, 25% would refer their HCV-infected patient to a PA, NP, or other MD in their practice, 22% would refer to an "HCV expert," and 1% would refer to an ID specialist. Respondents who reported "minimal knowledge of DAA agents" were more likely to consider the AMA their primary professional organization (20 vs. 1% AGA/AASLD (p = 0.001)), or be in a private practice not associated with a medical school (83 vs. 17% practice or hospital associated with a medical school p = 0.0001).
Discussion
Emerging data suggest that direct-acting antiviral therapies against HCV (DAA) will provide improved response rates when given in combination with currently available therapies. The enthusiasm for these new treatments must be tempered by realistic concerns including side-effects as well as the threat of viral resistance induced by these agents. We hypothesized that concern regarding these issues might affect attitudes of future use of DAA therapies by health care providers who currently treat HCV. The goal of the current study was to query a group of experienced HCV treaters using an Internet-based survey to assess attitudes regarding current and future treatment of HCV and correlate these responses related to focus of clinical practice, academic versus private practice, professional affiliation, and experience with DAA agents in clinical trials. US-based members of the AGA and AASLD were targeted for the survey as they represent the majority of HCV treaters in the US and a group most likely to have knowledge of DAA therapy. This manuscript represents the first description of attitudes regarding future use of DAA agents in a large group of experienced HCV treaters.
Based on responses to this survey, although the majority of current HCV treaters would prescribe a DAA agent, a significant number of respondents who treat HCV today (85%) would not initiate therapy when these agents became available in the future (81%). The decreased use of DAA therapies may be offset somewhat by an increase in referrals to a more experienced HCV treater, as more respondents would refer their patients to a "hepatitis C expert" after DAA agents became available in the future compared to referring patients if they were diagnosed with HCV today (10% versus 6%). Not surprisingly, future use of DAA therapy appears to be significant in treaters who identify themselves as Hepatologists, and those with experience using these agents in clinical trials. Moreover, direct clinical experience with DAAs did not appear to dampen the enthusiasm for future use of these agents, as 90% of respondents who participated in clinical trials with a DAA agent would utilize these agents to treat an HCV-infected patient when these agents became available.
We hypothesized that as infectious disease specialists have extensive experience prescribing oral antiviral agents for HIV, referrals to these providers would increase when DAA agents became available for HCV. Our hypothesis was clearly inaccurate as respondents to the survey were unlikely to refer their HCV-infected patients to an infectious disease specialist when faced with an HCV-infected patient today (1%) and when DAA agents were available in the future (0.8%). This trend was maintained even in respondents with minimal knowledge of DAA agents. Finally, a concerning observation was identified when assessing responses to the survey stratified by past experience with DAA therapy. Although a significant percentage of respondents who participated in clinical trials with a DAA (90%) or who were "aware or very aware" of these agents but did not participate in a clinical trial (81%) would use these agents in the future, more than half of respondents (52%) who reported minimal knowledge of DAA agents stated that they would also use them in the future. Although providers with minimal knowledge of DAA agents represented a small percentage of respondents to the survey, concern exists regarding the inappropriate use of DAAs in the future including inexperience with side-effect management, and lack of recognition of both treatment failure as well as the emergence of viral resistance [11-16]. It is therefore apparent to the authors of this manuscript that extensive education of all future prescribers of DAA agents will be required to ensure successful use of these therapies.
There are limitations of this study that are unfortunately shared by other surveys utilizing similar data collection and analyses techniques. Any Internet-based survey is limited by response rate, which is affected both by the ability to deliver the survey and the willingness of the survey recipient to accurately respond to the queries posed to them. Although 21% of recipients of the survey responded, it is possible that the identified results would have been different if more individuals completed the survey. Unfortunately, the large volume of unsolicited e-mail has induced the use of blockers and filters, thus potentially limiting the response rates to the survey. However, we believe that these limitations were balanced by several strengths including the overall brevity of the survey (nine questions) increasing the likelihood that those who received and opened the survey fully completed it, and by the target audience which represented a significant number of current HCV treaters with the highest likelihood of having knowledge regarding DAA agents.
In summary, the responses to this Internet-based survey of more than 1,000 current HCV treaters indicated that although the majority of respondents appear ready to utilize DAA agents in the future, referrals to "hepatitis C experts" will increase when these agents become available. In addition, future referrals to ID specialists appear to be limited. Finally, as more than half of respondents to the survey with "minimal knowledge" of DAA therapies also appear to be willing to utilize these compounds in the future, significant provider education will be required to minimize inappropriate use of these agents.
Conflict of interest Paul J. Gaglio, MD, Speakers Bureau, Merck; has received study support from Schering Plough (now Merck) and Vertex Pharmaceuticals. Noah Moss, MD: No Camille Baugh, MD: No Disclosures Noah Moss, MD: No Disclosures John Reinus, MD has received study support from Vertex Pharmaceuticals.
Source
March 9, 2011
Telapravir Promotes Early Clearance of HCV RNA With PEG-IFN/RBV, Early Response Predicts Outcome (weeks 1,2,4)
Download the pdf here
18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston
Mark Mascolini
"Patients treated with a telaprevir-based regimen, who had early HCV RNA undetectability, had higher sustained viral response rates......Among telapravir-treated people with undetectable HCV RNA after 1 week of therapy, 90% attained a sustained virologic response (SVR, undetectable HCV RNA 6 months after treatment ends), if undetectable at week 2 83% achieved SVR, and if undetectable at week 4 77% achieved SVR."
"More patients were undetectable for HCV RNA at early timepoints when treated with a telaprevir-based regimen.
-- 6%, 22%, and 20% of T12PR patients had first undetectable HCV RNA at Week 1, Week 2, and Week 4, respectively.
-- 2%, 3%, and 3% of patients treated with peginterferon alfa-2a/ribavirin alone had first undetectable HCV RNA at Week 1, Week 2, and Week 4, respectively."
"Regardless of treatment regimen, patients with early HCV RNA undetectability had higher sustained viral response rates, however, as stated above, fewer patients treated with peginterferon alfa-2a/ribavirin alone had undetectable HCV RNA at early viral timepoints compared to patients who received telaprevir-based regimen."
"A majority of patients treated with a telaprevir-based regimen received 24 weeks of total treatment while all patients treated with peginterferon alfa-2a/ribavirin alone received 48 weeks of total treatment.5,6"
"There were low discontinuation rates of all study drugs due to rash and anemia events during the telaprevir treatment phase with overall discontinuation rates due to adverse events of 7% and 4% in T12PR and peginterferon alfa-2a/ribavirin patients respectively."
----------------------------------
Adding telapravir to pegylated-interferon/ribavirin (PEG-IFN/RBV) lowered HCV RNA to undetectable levels more often in the first 4 weeks of therapy than PEG-IFN/RBV alone in HCV type 1-infected people enrolled in two large clinical trials [1]. Among telapravir-treated people with undetectable HCV RNA after 1 week of therapy, 90% attained a sustained virologic response (SVR, undetectable HCV RNA 6 months after treatment ends), if undetectable at week 2 83% achieved SVR, and if undetectable at week 4 77% achieved SVR.
Phase 3 trials of telapravir demonstrate that adding this HCV NS3-4A protease inhibitor to PEG-IFN/RBV significantly improves SVR and usually trims treatment duration to 24 weeks. This retrospective analysis pooled patients enrolled in two phase 3 telapravir trials: ADVANCE was a randomized placebo-controlled trial of telapravir plus PEG-IFN/RBV in HCV genotype 1-infected treatment-naive people. ILLUMINATE was an open-label noninferiority trial that compared telapravir response at 24 and 48 weeks in genotype 1-infected treatment-naive people who had undetectable HCV RNA at weeks 4 and 12.
Study participants had to be 18 to 70 years old and to have evidence of chronic hepatitis by liver biopsy within 1 year of screening for these studies. People with compensated liver cirrhosis were included. HCV RNA levels were measured on day 1 and at weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 36, 40, and 48 with an assay that has a detection limit of 25 IU/mL.
The pooled analysis included 903 people from ADVANCE or ILLUMINATE who were treated with telapravir plus PEG-IFN/RBV for 12 weeks and for either 24 or 48 weeks with PEG-IFN/RBV. The investigators compared them with 361 people who received only PEG-IFN/RBV in ADVANCE. Both the telapravir group and the PEG-IFN/RBV-only group had a higher proportion of men than women (60% and 58%) and a higher proportion of Caucasians than other races (83% and 88%). Median age (50 years) and body mass index (27 and 26 kg/m[2]) were equivalent in the two groups, and similar proportions began treatment with HCV RNA levels at or above 800,000 IU/mL (80% and 77%). Most people in both groups (75% and 80%) did not have bridging fibrosis or cirrhosis.
After 1, 2, and 4 weeks of treatment, much higher proportions in the telapravir group than the PEG-IFN/RBV-only group had undetectable HCV RNA:
Week 1: 6% versus 2%
Week 2: 22% versus 3%
Week 4: 20% versus 3%
Rapid virologic response (undetectable HCV RNA at week 4), extended rapid virologic response (undetectable at weeks 4 and 12), and SVR were greater with telapravir plus PEG-IFN/RBV (70%, 63%, and 73%) than with PEG-IFN/RBV alone (9%, 8%, and 44%).
Regardless of treatment arm, everyone with undetectable HCV RNA at week 1 (58 of 58 on telapravir and 7 of 7 on PEG-IFN/RBV alone) had undetectable HCV RNA at the end of treatment. Fifty-two of 58 people in the telapravir group (90%) and 7 of 7 in the PEG-IFN/RBV-only group who had undetectable HCV RNA at week 1 achieved SVR. In the telapravir group, 83% with undetectable HCV RNA at week 2 and 77% undetectable at week 4 attained SVR.
Among 903 people in the telapravir group, 66 (7%) experienced virologic failure, compared with 115 of 361 (32%) in the PEG-IFN/RBV-only group. Relapse rates were 8% with telapravir and 28% with PEG-IFN RBV only.
Side effects proved more frequent with telapravir-containing therapy. Compared with the PEG-IFN/RBV-only group, higher proportion in the telapravir group had itching (50% versus 36%), nausea (45% versus 31%), anemia (38% versus 17%), and rash (37% versus 24%). Throughout treatment, 14% in the telapravir group and 7% in the PEG-IFN/RBV group stopped all study drugs. (from Jules: the side effects profile is as expected, no unexpected reports).
This poster is online at the link provided in the reference
Source
18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston
Mark Mascolini
"Patients treated with a telaprevir-based regimen, who had early HCV RNA undetectability, had higher sustained viral response rates......Among telapravir-treated people with undetectable HCV RNA after 1 week of therapy, 90% attained a sustained virologic response (SVR, undetectable HCV RNA 6 months after treatment ends), if undetectable at week 2 83% achieved SVR, and if undetectable at week 4 77% achieved SVR."
"More patients were undetectable for HCV RNA at early timepoints when treated with a telaprevir-based regimen.
-- 6%, 22%, and 20% of T12PR patients had first undetectable HCV RNA at Week 1, Week 2, and Week 4, respectively.
-- 2%, 3%, and 3% of patients treated with peginterferon alfa-2a/ribavirin alone had first undetectable HCV RNA at Week 1, Week 2, and Week 4, respectively."
"Regardless of treatment regimen, patients with early HCV RNA undetectability had higher sustained viral response rates, however, as stated above, fewer patients treated with peginterferon alfa-2a/ribavirin alone had undetectable HCV RNA at early viral timepoints compared to patients who received telaprevir-based regimen."
"A majority of patients treated with a telaprevir-based regimen received 24 weeks of total treatment while all patients treated with peginterferon alfa-2a/ribavirin alone received 48 weeks of total treatment.5,6"
"There were low discontinuation rates of all study drugs due to rash and anemia events during the telaprevir treatment phase with overall discontinuation rates due to adverse events of 7% and 4% in T12PR and peginterferon alfa-2a/ribavirin patients respectively."
----------------------------------
Adding telapravir to pegylated-interferon/ribavirin (PEG-IFN/RBV) lowered HCV RNA to undetectable levels more often in the first 4 weeks of therapy than PEG-IFN/RBV alone in HCV type 1-infected people enrolled in two large clinical trials [1]. Among telapravir-treated people with undetectable HCV RNA after 1 week of therapy, 90% attained a sustained virologic response (SVR, undetectable HCV RNA 6 months after treatment ends), if undetectable at week 2 83% achieved SVR, and if undetectable at week 4 77% achieved SVR.
Phase 3 trials of telapravir demonstrate that adding this HCV NS3-4A protease inhibitor to PEG-IFN/RBV significantly improves SVR and usually trims treatment duration to 24 weeks. This retrospective analysis pooled patients enrolled in two phase 3 telapravir trials: ADVANCE was a randomized placebo-controlled trial of telapravir plus PEG-IFN/RBV in HCV genotype 1-infected treatment-naive people. ILLUMINATE was an open-label noninferiority trial that compared telapravir response at 24 and 48 weeks in genotype 1-infected treatment-naive people who had undetectable HCV RNA at weeks 4 and 12.
Study participants had to be 18 to 70 years old and to have evidence of chronic hepatitis by liver biopsy within 1 year of screening for these studies. People with compensated liver cirrhosis were included. HCV RNA levels were measured on day 1 and at weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 36, 40, and 48 with an assay that has a detection limit of 25 IU/mL.
The pooled analysis included 903 people from ADVANCE or ILLUMINATE who were treated with telapravir plus PEG-IFN/RBV for 12 weeks and for either 24 or 48 weeks with PEG-IFN/RBV. The investigators compared them with 361 people who received only PEG-IFN/RBV in ADVANCE. Both the telapravir group and the PEG-IFN/RBV-only group had a higher proportion of men than women (60% and 58%) and a higher proportion of Caucasians than other races (83% and 88%). Median age (50 years) and body mass index (27 and 26 kg/m[2]) were equivalent in the two groups, and similar proportions began treatment with HCV RNA levels at or above 800,000 IU/mL (80% and 77%). Most people in both groups (75% and 80%) did not have bridging fibrosis or cirrhosis.
After 1, 2, and 4 weeks of treatment, much higher proportions in the telapravir group than the PEG-IFN/RBV-only group had undetectable HCV RNA:
Week 1: 6% versus 2%
Week 2: 22% versus 3%
Week 4: 20% versus 3%
Rapid virologic response (undetectable HCV RNA at week 4), extended rapid virologic response (undetectable at weeks 4 and 12), and SVR were greater with telapravir plus PEG-IFN/RBV (70%, 63%, and 73%) than with PEG-IFN/RBV alone (9%, 8%, and 44%).
Regardless of treatment arm, everyone with undetectable HCV RNA at week 1 (58 of 58 on telapravir and 7 of 7 on PEG-IFN/RBV alone) had undetectable HCV RNA at the end of treatment. Fifty-two of 58 people in the telapravir group (90%) and 7 of 7 in the PEG-IFN/RBV-only group who had undetectable HCV RNA at week 1 achieved SVR. In the telapravir group, 83% with undetectable HCV RNA at week 2 and 77% undetectable at week 4 attained SVR.
Among 903 people in the telapravir group, 66 (7%) experienced virologic failure, compared with 115 of 361 (32%) in the PEG-IFN/RBV-only group. Relapse rates were 8% with telapravir and 28% with PEG-IFN RBV only.
Side effects proved more frequent with telapravir-containing therapy. Compared with the PEG-IFN/RBV-only group, higher proportion in the telapravir group had itching (50% versus 36%), nausea (45% versus 31%), anemia (38% versus 17%), and rash (37% versus 24%). Throughout treatment, 14% in the telapravir group and 7% in the PEG-IFN/RBV group stopped all study drugs. (from Jules: the side effects profile is as expected, no unexpected reports).
This poster is online at the link provided in the reference
*Patients who met virologic stopping rule (Week 4 HCV RNA > 1000 IU/mL patients receiving telaprevir-based regimen were to discontinue telaprevir and continue PR, Week 12 HCV RNA < 2 log10 decrease compared to baseline, patients were to discontinue all study drugs, or Week 24 - 36 Detectable HCV RNA > 10 IU/mL patients were to discontinue all study drugs) or had detectable HCV RNA at end of completed treatment. · Overall 7% (66/903) of T12PR patients experienced virologic failure versus 32% (115/361) of PR patients.
· Overall 8% (64/903) of T12PR patients experienced relapse versus 28% (64/361) of PR patients (Table 2).
Reference
1. Sherman K, Everson G, Jacobson I, et al. Early clearance of HCV RNA in HCV genotype 1 treatment-naive patients treated with TVR, pegIFN, and RBV: pooled analysis of the phase 3 trials ADVANCE and ILLUMINATE. 18th Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. Abstract 957. http://www.retroconference.org/2011/PDFs/957.pdf.
Source
Long-Term Outcome After Antiviral Therapy of Patients With Hepatitis C Virus Infection and Decompensated Cirrhosis
Clinical Gastroenterology and Hepatology
Volume 9, Issue 3 , Pages 249-253, March 2011
Angelo Iacobellis, Francesco Perri, Maria Rosa Valvano, Nazario Caruso, Grazia Anna Niro, Angelo Andriulli
Abstract
Background & Aims
We evaluated the long-term outcomes after antiviral therapy of patients with decompensated cirrhosis and hepatitis C virus (HCV) infection.
Methods
Seventy-five patients with HCV infection and decompensated cirrhosis received therapy with peginterferon alfa-2b and ribavirin. We compared adverse-event profiles and mortality rates between patients with or without sustained virologic responses (SVRs). The mean follow-up time off therapy was 51 ± 18 months (range, 3–78 months).
Results
Seven patients with HCV genotypes 1 or 4 (16%) and 17 patients with genotypes 2 or 3 (55%) achieved SVRs. The mean survival times were 53 months among patients who did not achieve SVRs (95% confidence interval [CI], 48–59 months) and 73 months among those who did achieve SVRs (95% CI, 67–80 months) (P = .004). During the study, 25 patients died (2 with and 23 without SVRs). During the follow-up period, 8 of 24 patients with SVRs (33.3%) and 49 of 51 without SVRs (96.1%) experienced further events of decompensation (P < .0001). The hospital readmission rates for patients with and without SVRs were 7.4 and 56 per 1000 person-months, respectively (ratio of 7.5 without/with SVR; 95% CI, 4.0–16.0; P < .0001). At the end of the follow-up period, the incidence of hepatocellular carcinoma was not associated with clearance of HCV.
Conclusions
Among patients with cirrhosis that is a result of HCV infection and who have progressed to a stage of liver decompensation, an SVR after antiviral therapy is a positive prognostic factor.
Keywords: Liver Disease, Clinical Trial, Chronic Hepatitis, Peg-IFN
Source
Volume 9, Issue 3 , Pages 249-253, March 2011
Angelo Iacobellis, Francesco Perri, Maria Rosa Valvano, Nazario Caruso, Grazia Anna Niro, Angelo Andriulli
Abstract
Background & Aims
We evaluated the long-term outcomes after antiviral therapy of patients with decompensated cirrhosis and hepatitis C virus (HCV) infection.
Methods
Seventy-five patients with HCV infection and decompensated cirrhosis received therapy with peginterferon alfa-2b and ribavirin. We compared adverse-event profiles and mortality rates between patients with or without sustained virologic responses (SVRs). The mean follow-up time off therapy was 51 ± 18 months (range, 3–78 months).
Results
Seven patients with HCV genotypes 1 or 4 (16%) and 17 patients with genotypes 2 or 3 (55%) achieved SVRs. The mean survival times were 53 months among patients who did not achieve SVRs (95% confidence interval [CI], 48–59 months) and 73 months among those who did achieve SVRs (95% CI, 67–80 months) (P = .004). During the study, 25 patients died (2 with and 23 without SVRs). During the follow-up period, 8 of 24 patients with SVRs (33.3%) and 49 of 51 without SVRs (96.1%) experienced further events of decompensation (P < .0001). The hospital readmission rates for patients with and without SVRs were 7.4 and 56 per 1000 person-months, respectively (ratio of 7.5 without/with SVR; 95% CI, 4.0–16.0; P < .0001). At the end of the follow-up period, the incidence of hepatocellular carcinoma was not associated with clearance of HCV.
Conclusions
Among patients with cirrhosis that is a result of HCV infection and who have progressed to a stage of liver decompensation, an SVR after antiviral therapy is a positive prognostic factor.
Keywords: Liver Disease, Clinical Trial, Chronic Hepatitis, Peg-IFN
Source
New instrument for analyzing viruses
Public release date: 8-Mar-2011
Contact: Ellen R. Weiss
eweiss@biophysics.org
240-290-5606
American Institute of Physics
Sensitive 'PING' device described at Biophysical Meeting today in Baltimore
WASHINGTON, D.C. (March 8, 2011) -- Scientists in Israel and California have developed an instrument for rapidly analyzing molecular interactions that take place viruses and the cells they infect. By helping to identify interactions between proteins made by viruses like HIV and hepatitis and proteins made by the human cells these viruses infect, the device may help scientists develop new ways of disrupting these interactions and find new drugs for treating those infections.
According to Doron Gerber, a professor at Bar Ilan University in Ramat Gan, the PING system (Protein Interaction Network Generator) can be used to examine thousands of potential interactions at a time, and it detects them at a sensitivity 100- to 1,000-time greater than current methods. Gerber developed PING with collaborators at Stanford University, and he will describe the technology today at the 55th Annual Biophysical Society Meeting in Baltimore.
When a virus infects a human cell, it hijacks the machinery of that cell, recruiting certain host proteins and subverting them to the task of manufacturing new viral particles. This feature of viral biology has made viral infections notoriously difficult to treat, as therapies must specifically target the virus without harming the cell.
One approach that has been successful is to identify key interactions between viral and host proteins, which can then serve as targets for new drugs. For example, the HIV drug Fuzeon works by blocking a viral protein from attaching to proteins on the surface of immune system cells, barring entry to the cell. Like many antivirals, Fuzeon is used in combination with other drugs in a "cocktail." This is because, like most viruses, HIV mutates rapidly, acquiring resistance to individual drugs. Therefore, the need for new antiviral drugs is constant and ongoing.
Using PING, the Israeli and California scientists identified novel cellular partners for proteins from hepatitis C and hepatitis D. "And we can now use the same system to screen for inhibitors," says Gerber, who adds that new treatments are urgently needed for hepatitis C, for which only one treatment exists that works in only half the patient population.
Because PING employs microfluidics, very small samples can be used; gathering enough material has been a particular challenge with existing methods.
###
The presentation, "Mapping Virus-Host Protein Interactions Using the PING Microfluidics Platform," is at 5:00 p.m. on Tuesday, March 8, 2011 in Room 307 of the Baltimore Convention Center. ABSTRACT: http://tinyurl.com/67lnomy
The research was funded by the NIH Pioneer grant.
MORE MEETING INFORMATION
Each year, the Biophysical Society Annual Meeting brings together more than 6,000 scientists and hosts more than 4,000 poster presentations, 200 exhibits, and more than 20 symposia. The largest meeting of its type in the world, the Biophysical Society Annual Meeting retains its small-meeting flavor through its subgroup meetings, platform sessions, social activities, and committee programs.
QUICK LINKS
Meeting Home Page: http://www.biophysics.org/2011meeting
General Meeting Information: http://www.biophysics.org/GeneralInfo/Overview/tabid/2062/Default.aspx
Search abstracts: http://www.abstractsonline.com/plan/start.aspx?mkey={FEA830A5-24AD-47F3-8E61-FCA29F5FEF34}
PRESS REGISTRATION
The Biophysical Society invites credentialed journalists, freelance reporters working on assignment, and public information officers to attend its Annual Meeting for free. For more information on registering as a member of the press, please contact Ellen Weiss at eweiss@biophysics.org or 240-290-5606. Also see: http://www.biophysics.org/Registration/Press/tabid/2148/Default.aspx
ABOUT THE BIOPHYSICAL SOCIETY
The Biophysical Society, founded in 1956, is a professional, scientific society established to encourage development and dissemination of knowledge in biophysics. The society promotes growth in this expanding field through its annual meeting, monthly journal, and committee and outreach activities. Its over 9,000 members are located throughout the U.S. and the world, where they teach and conduct research in colleges, universities, laboratories, government agencies, and industry. For more information on the society or the 2011 Annual Meeting, visit http://www.biophysics.org/
Source
Contact: Ellen R. Weiss
eweiss@biophysics.org
240-290-5606
American Institute of Physics
Sensitive 'PING' device described at Biophysical Meeting today in Baltimore
WASHINGTON, D.C. (March 8, 2011) -- Scientists in Israel and California have developed an instrument for rapidly analyzing molecular interactions that take place viruses and the cells they infect. By helping to identify interactions between proteins made by viruses like HIV and hepatitis and proteins made by the human cells these viruses infect, the device may help scientists develop new ways of disrupting these interactions and find new drugs for treating those infections.
According to Doron Gerber, a professor at Bar Ilan University in Ramat Gan, the PING system (Protein Interaction Network Generator) can be used to examine thousands of potential interactions at a time, and it detects them at a sensitivity 100- to 1,000-time greater than current methods. Gerber developed PING with collaborators at Stanford University, and he will describe the technology today at the 55th Annual Biophysical Society Meeting in Baltimore.
When a virus infects a human cell, it hijacks the machinery of that cell, recruiting certain host proteins and subverting them to the task of manufacturing new viral particles. This feature of viral biology has made viral infections notoriously difficult to treat, as therapies must specifically target the virus without harming the cell.
One approach that has been successful is to identify key interactions between viral and host proteins, which can then serve as targets for new drugs. For example, the HIV drug Fuzeon works by blocking a viral protein from attaching to proteins on the surface of immune system cells, barring entry to the cell. Like many antivirals, Fuzeon is used in combination with other drugs in a "cocktail." This is because, like most viruses, HIV mutates rapidly, acquiring resistance to individual drugs. Therefore, the need for new antiviral drugs is constant and ongoing.
Using PING, the Israeli and California scientists identified novel cellular partners for proteins from hepatitis C and hepatitis D. "And we can now use the same system to screen for inhibitors," says Gerber, who adds that new treatments are urgently needed for hepatitis C, for which only one treatment exists that works in only half the patient population.
Because PING employs microfluidics, very small samples can be used; gathering enough material has been a particular challenge with existing methods.
###
The presentation, "Mapping Virus-Host Protein Interactions Using the PING Microfluidics Platform," is at 5:00 p.m. on Tuesday, March 8, 2011 in Room 307 of the Baltimore Convention Center. ABSTRACT: http://tinyurl.com/67lnomy
The research was funded by the NIH Pioneer grant.
MORE MEETING INFORMATION
Each year, the Biophysical Society Annual Meeting brings together more than 6,000 scientists and hosts more than 4,000 poster presentations, 200 exhibits, and more than 20 symposia. The largest meeting of its type in the world, the Biophysical Society Annual Meeting retains its small-meeting flavor through its subgroup meetings, platform sessions, social activities, and committee programs.
QUICK LINKS
Meeting Home Page: http://www.biophysics.org/2011meeting
General Meeting Information: http://www.biophysics.org/GeneralInfo/Overview/tabid/2062/Default.aspx
Search abstracts: http://www.abstractsonline.com/plan/start.aspx?mkey={FEA830A5-24AD-47F3-8E61-FCA29F5FEF34}
PRESS REGISTRATION
The Biophysical Society invites credentialed journalists, freelance reporters working on assignment, and public information officers to attend its Annual Meeting for free. For more information on registering as a member of the press, please contact Ellen Weiss at eweiss@biophysics.org or 240-290-5606. Also see: http://www.biophysics.org/Registration/Press/tabid/2148/Default.aspx
ABOUT THE BIOPHYSICAL SOCIETY
The Biophysical Society, founded in 1956, is a professional, scientific society established to encourage development and dissemination of knowledge in biophysics. The society promotes growth in this expanding field through its annual meeting, monthly journal, and committee and outreach activities. Its over 9,000 members are located throughout the U.S. and the world, where they teach and conduct research in colleges, universities, laboratories, government agencies, and industry. For more information on the society or the 2011 Annual Meeting, visit http://www.biophysics.org/
Source
University Hospitals tests experimental HIV vaccine
12:05 AM, Mar 9, 2011
Written by Monica Robins
CLEVELAND -- The Case Western Reserve University/University Hospitals AIDS Clinical Trials Unit is now screening potential participants for a nationwide HIV vaccine clinical trial (HVTN505) being conducted by the HIV Vaccine Trials Network.
The HIV vaccine trial is the first of its kind in Cleveland since 2003.
The trial is testing the safety and effectiveness of a combination of two HIV vaccines to see if they will stimulate an immune response to HIV or decrease the amount of virus in the blood if a person later becomes infected.
Neither vaccine can cause HIV infection.
The trial, which also is open in 15 other U.S. cities, is looking to enroll 1,350 gay men and transgender women. Participants must be 18-50 years old and HIV-uninfected (negative).
People interested in learning more about the vaccine trial should call 216-844-4444.
The vaccine trial comes to Cleveland after a year of promising developments in the worldwide search for effective new tools to help stem the AIDS epidemic, now entering its third decade.
Last year, clinical trials proved some level of effectiveness for two HIV prevention strategies. The CAPRISA004 study demonstrated for the first time that a microbicide - a gel used by a woman prior to sexual activity, could reduce a woman's risk of acquiring HIV.
Another clinical trial showed that antiretroviral drugs - used to treat people living with HIV - can reduce a person's risk of acquiring HIV if used consistently prior to sexual contact.
The Case Western Reserve/UH AIDS Clinical Trials Unit has been conducting AIDS-related clinical research since its founding in 1987.
Source
March 8, 2011
Telaprevir, Boceprevir Boost SVR in Hep C
Perspective: We are on the verge of triple-drug regimens that will improve response rates for genotype 1 hepatitis C to where rates for genotype 2/3 have been, while shortening the duration of therapy to 24 weeks for many patients, which can lower both cost and side effects. However, therapy will be more complex and will require closer monitoring to manage side effects and monitor for and prevent resistance.
DR. ROBERT S. BROWN JR. is the Frank Cardile Professor of Medicine and Surgery and Chief of the Center for Liver Disease and Transplantation at Columbia University College of Physicians and Surgeons, New York.
BY DIANA MAHONEY
Elsevier Global Medical News
BOSTON – The forthcoming availability of the protease inhibitors telaprevir and boceprevir for the treatment of chronic hepatitis C is likely to vastly improve virologic response rates and cut treatment times, but experts warn that such advancements need to be balanced against the huge potential for misuse of the agents and the need to manage side effects and monitor for antiviral resistance.
When used in combination with standard therapy consisting of pegylated interferon plus ribavirin, each of these investigational drugs improved sustained virologic response (SVR) rates and reduced treatment duration, compared with standard therapy alone, in four pivotal, phase III trials reported at the annual meeting of the American Association for the Study of Liver Diseases.
Previous Nonresponders Benefit From Boceprevir
Response-guided, fixed-duration therapy with boceprevir was safe and effective in a cohort of HCV genotype 1 patients who were enrolled in the RESPOND-2 study and who failed standard therapy, said lead investigator Dr. Bruce R. Bacon of St. Louis University. The 403 patients included those in whom prior standard therapy resulted in either a partial response (HCV RNA less than 2 logs at 12 weeks but still positive) or a relapse, he said.
All patients underwent a 4- week lead-in phase of standard therapy followed by random assignment to continue standard therapy alone or in conjunction with 800 mg of boceprevir taken three times daily.
The treatment duration was 36 weeks for patients in the boceprevir arm with undetectable HCV RNA at study weeks 8 and 12, whereas those patients in whom HCV RNA was detectable at study week 8, but undetectable at week 12, stopped boceprevir at week 36 but continued standard therapy for an additional 12 weeks (total of 48 weeks). Controls were treated for 48 weeks.
The SVR rates at 24 weeks after treatment conclusion were significantly higher in the boceprevir groups, compared with the control group. In the responseguided and fixed-duration boceprevir groups, the SVR rates were 59% and 66%, respectively, compared with 21% in the control patients, Dr. Bacon said.
In the two boceprevir study arms, “previous historical relapsers and partial responders fared better than the patients receiving standard of care,” he noted.
Although the rates of anemia were significantly higher in the boceprevir arms, “the rate of treatment discontinuation related to side effects was similar across all three arms,” Dr. Bacon reported, possibly because the use of erythropoietin was allowed to treat anemia, he said.
The findings of this study answer an important question about response-guided therapy “by confirming that many patients can be treated successfully with a treatment duration that is reduced by 3 months relative to the current standard of care treatment,” Dr. Bacon said.
Boceprevir with a standard therapy lead-in strategy was also evaluated in the SPRINT-2 study involving HCV genotype 1 treatment-naive patients, according to Dr. Fred Poordad of Cedars-Sinai Medical Center in Los Angeles. The trial included 1,097 patients who underwent a similar 4-week standard therapy lead-in as defined above, followed by the addition of placebo for 44 more weeks or by the addition of boceprevir, either for 24 more weeks for patients with undetectable HCV RNA at week 8 or for 24 more weeks plus 20 additional weeks of standard therapy for patients with detectable HCV RNA at week 8, but not at week 24, Dr. Poordad explained. Patients with detectable HCV RNA at week 24 were discontinued for futility, he said.
“In both the response-guided and fixed-treatment arms, boceprevir increased viral cure rates significantly, by approximately 70%,” Dr. Poordad stated. The SVR rate was 63% in the 28-week response-guided group, 66% in the 48-week fixed-duration group, and 38% in the 48-week control group, he said.
In a cohort analysis of treatment response for the study’s 159 black patients, the relative improvement in SVR rates remained significant in the boceprevir arms, although the differences were not as robust, Dr. Poordad said. In this subgroup, the respective SVR rates in the response- guided therapy, fixed-duration therapy, and control groups were 42%, 53%, and 23%.
The rationale for using a lead-in strategy “is to help physicians identify patient responsiveness to interferon before adding boceprevir,” Dr. Poordad said. This can provide an early indication of the likelihood of treatment success. The advantage of subsequent response-guided therapy, he noted, is that it enables physicians to be flexible in managing their patients’ therapy “by adapting treatment duration to individual patient response.”
Telaprevir Boosts Viral Cure Rates
In the ADVANCE trial, a three-arm, double-blind, placebo-controlled study, investigators compared two telaprevir-based regimens with standard therapy in 1,088 treatment-naive patients with chronic genotype 1 hepatitis C virus (HCV) infection, according to lead investigator Dr. Ira M. Jacobson, AGAF, of New York Weill Cornell Medical Center in New York City.
Patients in treatment arms 1 and 2 received 750 mg of telaprevir plus standard therapy for 8 and 12 weeks, respectively, whereas patients in the control group received standard therapy alone, which consisted of 180 mcg/week of pegylated interferon alfa-2a and 1,000-1,200 mg/day of ribavirin.
Patients who had extended, rapid virologic response (RVR) – defined as undetectable HCV RNA viral load at treatment weeks 4 and 12 – were treated with standard therapy for an additional 16 and 12 weeks in the 8- and 12-week telaprevir arms, respectively, for a total of 24 weeks, Dr. Jacobson explained. Patients in whom HCV RNA was detectable at either week 4 or 12 received an additional 40 and 36 weeks of therapy, respectively, for a total of 48 weeks. The control group underwent standard therapy for 48 weeks.
Compared with 44% of patients in the control group who achieved SVR 24 weeks after the last treatment, significantly more patients in both telaprevir arms – 69% of the 8-week group and 75% of the 12-week group – met that end point, Dr. Jacobson reported. The extended RVR rates in the 8- and 12-week groups were 57% and 58%, respectively, compared with 8% in the control arm.
Significantly improved SVRs were also observed in difficult-to-treat subgroups. “Among black patients, the [SVR] rates were 58% and 62% in the 8- and 12-week treatment arms, and 25% in the control arm, and in cirrhotic patients the respective rates were 53%, 62%, and 33%,” he said. Rates of treatment discontinuation due to adverse events, such as rash and anemia, were 8% and 7% in the 8-and 12-week telaprevir groups and 4% in the control group, “which is an improvement, compared with the previously reported profile,” he said.
The phase III, open-label ILLUMINATE trial was designed to determine whether extending the telaprevir and standard therapy regimen from 24 to 48 weeks would be beneficial in treatment-naive, genotype 1 HCV patients who achieved extended RVR. In all, 540 patients were initially treated with the 12-week telaprevir regimen described above. Of the 352 patients who achieved RVR, 322 remained on treatment and were randomized to either a 24-week or 48-week treatment arm.
“The [SVR] rates associated with the 24-week and the 48-week arms were statistically similar, at 92% and 87.5%, respectively,” reported Dr. Kenneth E. Sherman of the University of Cincinnati. Analyses of the data based on race and extent of liver damage showed that 88% of black patients who had extended RVR achieved SVR in both the 24- and 48- week treatment arms, and 82% and 88% of patients with advanced fibrosis/cirrhosis achieved SVR in the 24-week and 48-week arms, respectively, he said.
There were more adverse event–related treatment discontinuations in the longertreatment group (12.5% vs. 0.6%), suggesting a benefit to the shorter duration, Dr. Sherman said. The high viral cure rate observed in the study – the overall SVR rate was 72% in an intent-to-treat analysis – “[supports] the role of response-guided therapy with telaprevir-based regimens” in treatment-naive patients,” he said.
All the sources disclosed relationships with numerous pharmaceutical companies. Among them, Dr. Jacobson and Dr. Sherman disclosed relationships with Vertex Pharmaceuticals, which manufactures telaprevir. Dr. Jacobson also has a relationship with Tibotec, which also is involved with the development of telaprevir. Dr. Poordad and Dr. Bacon also disclosed relationships with Merck, which manufactures boceprevir.
Source
DR. ROBERT S. BROWN JR. is the Frank Cardile Professor of Medicine and Surgery and Chief of the Center for Liver Disease and Transplantation at Columbia University College of Physicians and Surgeons, New York.
BY DIANA MAHONEY
Elsevier Global Medical News
BOSTON – The forthcoming availability of the protease inhibitors telaprevir and boceprevir for the treatment of chronic hepatitis C is likely to vastly improve virologic response rates and cut treatment times, but experts warn that such advancements need to be balanced against the huge potential for misuse of the agents and the need to manage side effects and monitor for antiviral resistance.
When used in combination with standard therapy consisting of pegylated interferon plus ribavirin, each of these investigational drugs improved sustained virologic response (SVR) rates and reduced treatment duration, compared with standard therapy alone, in four pivotal, phase III trials reported at the annual meeting of the American Association for the Study of Liver Diseases.
Previous Nonresponders Benefit From Boceprevir
Response-guided, fixed-duration therapy with boceprevir was safe and effective in a cohort of HCV genotype 1 patients who were enrolled in the RESPOND-2 study and who failed standard therapy, said lead investigator Dr. Bruce R. Bacon of St. Louis University. The 403 patients included those in whom prior standard therapy resulted in either a partial response (HCV RNA less than 2 logs at 12 weeks but still positive) or a relapse, he said.
All patients underwent a 4- week lead-in phase of standard therapy followed by random assignment to continue standard therapy alone or in conjunction with 800 mg of boceprevir taken three times daily.
The treatment duration was 36 weeks for patients in the boceprevir arm with undetectable HCV RNA at study weeks 8 and 12, whereas those patients in whom HCV RNA was detectable at study week 8, but undetectable at week 12, stopped boceprevir at week 36 but continued standard therapy for an additional 12 weeks (total of 48 weeks). Controls were treated for 48 weeks.
The SVR rates at 24 weeks after treatment conclusion were significantly higher in the boceprevir groups, compared with the control group. In the responseguided and fixed-duration boceprevir groups, the SVR rates were 59% and 66%, respectively, compared with 21% in the control patients, Dr. Bacon said.
In the two boceprevir study arms, “previous historical relapsers and partial responders fared better than the patients receiving standard of care,” he noted.
Although the rates of anemia were significantly higher in the boceprevir arms, “the rate of treatment discontinuation related to side effects was similar across all three arms,” Dr. Bacon reported, possibly because the use of erythropoietin was allowed to treat anemia, he said.
The findings of this study answer an important question about response-guided therapy “by confirming that many patients can be treated successfully with a treatment duration that is reduced by 3 months relative to the current standard of care treatment,” Dr. Bacon said.
Boceprevir with a standard therapy lead-in strategy was also evaluated in the SPRINT-2 study involving HCV genotype 1 treatment-naive patients, according to Dr. Fred Poordad of Cedars-Sinai Medical Center in Los Angeles. The trial included 1,097 patients who underwent a similar 4-week standard therapy lead-in as defined above, followed by the addition of placebo for 44 more weeks or by the addition of boceprevir, either for 24 more weeks for patients with undetectable HCV RNA at week 8 or for 24 more weeks plus 20 additional weeks of standard therapy for patients with detectable HCV RNA at week 8, but not at week 24, Dr. Poordad explained. Patients with detectable HCV RNA at week 24 were discontinued for futility, he said.
“In both the response-guided and fixed-treatment arms, boceprevir increased viral cure rates significantly, by approximately 70%,” Dr. Poordad stated. The SVR rate was 63% in the 28-week response-guided group, 66% in the 48-week fixed-duration group, and 38% in the 48-week control group, he said.
In a cohort analysis of treatment response for the study’s 159 black patients, the relative improvement in SVR rates remained significant in the boceprevir arms, although the differences were not as robust, Dr. Poordad said. In this subgroup, the respective SVR rates in the response- guided therapy, fixed-duration therapy, and control groups were 42%, 53%, and 23%.
The rationale for using a lead-in strategy “is to help physicians identify patient responsiveness to interferon before adding boceprevir,” Dr. Poordad said. This can provide an early indication of the likelihood of treatment success. The advantage of subsequent response-guided therapy, he noted, is that it enables physicians to be flexible in managing their patients’ therapy “by adapting treatment duration to individual patient response.”
Telaprevir Boosts Viral Cure Rates
In the ADVANCE trial, a three-arm, double-blind, placebo-controlled study, investigators compared two telaprevir-based regimens with standard therapy in 1,088 treatment-naive patients with chronic genotype 1 hepatitis C virus (HCV) infection, according to lead investigator Dr. Ira M. Jacobson, AGAF, of New York Weill Cornell Medical Center in New York City.
Patients in treatment arms 1 and 2 received 750 mg of telaprevir plus standard therapy for 8 and 12 weeks, respectively, whereas patients in the control group received standard therapy alone, which consisted of 180 mcg/week of pegylated interferon alfa-2a and 1,000-1,200 mg/day of ribavirin.
Patients who had extended, rapid virologic response (RVR) – defined as undetectable HCV RNA viral load at treatment weeks 4 and 12 – were treated with standard therapy for an additional 16 and 12 weeks in the 8- and 12-week telaprevir arms, respectively, for a total of 24 weeks, Dr. Jacobson explained. Patients in whom HCV RNA was detectable at either week 4 or 12 received an additional 40 and 36 weeks of therapy, respectively, for a total of 48 weeks. The control group underwent standard therapy for 48 weeks.
Compared with 44% of patients in the control group who achieved SVR 24 weeks after the last treatment, significantly more patients in both telaprevir arms – 69% of the 8-week group and 75% of the 12-week group – met that end point, Dr. Jacobson reported. The extended RVR rates in the 8- and 12-week groups were 57% and 58%, respectively, compared with 8% in the control arm.
Significantly improved SVRs were also observed in difficult-to-treat subgroups. “Among black patients, the [SVR] rates were 58% and 62% in the 8- and 12-week treatment arms, and 25% in the control arm, and in cirrhotic patients the respective rates were 53%, 62%, and 33%,” he said. Rates of treatment discontinuation due to adverse events, such as rash and anemia, were 8% and 7% in the 8-and 12-week telaprevir groups and 4% in the control group, “which is an improvement, compared with the previously reported profile,” he said.
The phase III, open-label ILLUMINATE trial was designed to determine whether extending the telaprevir and standard therapy regimen from 24 to 48 weeks would be beneficial in treatment-naive, genotype 1 HCV patients who achieved extended RVR. In all, 540 patients were initially treated with the 12-week telaprevir regimen described above. Of the 352 patients who achieved RVR, 322 remained on treatment and were randomized to either a 24-week or 48-week treatment arm.
“The [SVR] rates associated with the 24-week and the 48-week arms were statistically similar, at 92% and 87.5%, respectively,” reported Dr. Kenneth E. Sherman of the University of Cincinnati. Analyses of the data based on race and extent of liver damage showed that 88% of black patients who had extended RVR achieved SVR in both the 24- and 48- week treatment arms, and 82% and 88% of patients with advanced fibrosis/cirrhosis achieved SVR in the 24-week and 48-week arms, respectively, he said.
There were more adverse event–related treatment discontinuations in the longertreatment group (12.5% vs. 0.6%), suggesting a benefit to the shorter duration, Dr. Sherman said. The high viral cure rate observed in the study – the overall SVR rate was 72% in an intent-to-treat analysis – “[supports] the role of response-guided therapy with telaprevir-based regimens” in treatment-naive patients,” he said.
All the sources disclosed relationships with numerous pharmaceutical companies. Among them, Dr. Jacobson and Dr. Sherman disclosed relationships with Vertex Pharmaceuticals, which manufactures telaprevir. Dr. Jacobson also has a relationship with Tibotec, which also is involved with the development of telaprevir. Dr. Poordad and Dr. Bacon also disclosed relationships with Merck, which manufactures boceprevir.
Source
Antiviral activity, safety, and pharmacokinetics of danoprevir/ritonavir plus PEG-IFN α-2a/RBV in hepatitis C patients
J Hepatol. 2011 Feb 24. [Epub ahead of print]
Gane EJ, Rouzier R, Stedman C, Wiercinska-Drapalo A, Horban A, Chang L, Zhang Y, Sampeur P, NĂĄjera I, Smith P, Shulman NS, Tran JQ.
Auckland Clinical Studies, New Zealand.
Abstract
BACKGROUND AND AIMS: Danoprevir (RG7227; ITMN-191) is a potent inhibitor of the HCV NS3/4A serine protease. The aims of this double-blind, placebo-controlled, multiple-ascending dose phase Ib study were to evaluate safety, tolerability, antiviral activity, resistance and pharmacokinetics of once- and twice-daily danoprevir in the presence of low-dose ritonavir (danoprevir/r) and in combination with peginterferon alfa-2a (40KD)/ribavirin in treatment-naive HCV genotype 1 patients.
METHODS: Thirty eligible patients were enrolled into 3 cohorts and treated with danoprevir/r or placebo/r all in combination with peginterferon alfa-2a (40KD)/ribavirin for 15 days. Cohort 1 received danoprevir/r at 100/100mg twice daily; Cohort 2 200/100mg once daily; and Cohort 3 200/100mg twice daily.
RESULTS: The median reductions in HCV RNA from baseline after 14 days of treatment (day 15) were -5.1, -4.8 and -4.6 log(10) IU/mL in Cohorts 1, 2 and 3, respectively, and -2.7 log(10) in placebo/r and peginterferon alfa-2a (40KD)/ribavirin recipients. Viral breakthrough was not observed in any patient. On day 15 HCV RNA was undetectable (<15 IU/mL) in 6/9 (67%), 4/8 (50%) and 8/8 (100%) patients in Cohorts 1, 2 and 3 respectively. When co-administered with low dose ritonavir, danoprevir concentrations reached steady state between 6 to 10 days of dosing. Danoprevir exposures increased more than dose proportionally between 100/100 mg and 200/100 mg. Danoprevir/r plus peginterferon alfa-2a (40KD)/ribavirin was well-tolerated with no safety-related discontinuations.
CONCLUSIONS: Danoprevir/r plus peginterferon alfa-2a (40KD)/ribavirin provides profound and robust reductions in serum HCV RNA, at substantially lower systemic exposures compared to those observed with higher doses of danoprevir in the absence of ritonavir. These results support further studies of danoprevir/r.
Copyright © 2011. Published by Elsevier B.V.
Source
Gane EJ, Rouzier R, Stedman C, Wiercinska-Drapalo A, Horban A, Chang L, Zhang Y, Sampeur P, NĂĄjera I, Smith P, Shulman NS, Tran JQ.
Auckland Clinical Studies, New Zealand.
Abstract
BACKGROUND AND AIMS: Danoprevir (RG7227; ITMN-191) is a potent inhibitor of the HCV NS3/4A serine protease. The aims of this double-blind, placebo-controlled, multiple-ascending dose phase Ib study were to evaluate safety, tolerability, antiviral activity, resistance and pharmacokinetics of once- and twice-daily danoprevir in the presence of low-dose ritonavir (danoprevir/r) and in combination with peginterferon alfa-2a (40KD)/ribavirin in treatment-naive HCV genotype 1 patients.
METHODS: Thirty eligible patients were enrolled into 3 cohorts and treated with danoprevir/r or placebo/r all in combination with peginterferon alfa-2a (40KD)/ribavirin for 15 days. Cohort 1 received danoprevir/r at 100/100mg twice daily; Cohort 2 200/100mg once daily; and Cohort 3 200/100mg twice daily.
RESULTS: The median reductions in HCV RNA from baseline after 14 days of treatment (day 15) were -5.1, -4.8 and -4.6 log(10) IU/mL in Cohorts 1, 2 and 3, respectively, and -2.7 log(10) in placebo/r and peginterferon alfa-2a (40KD)/ribavirin recipients. Viral breakthrough was not observed in any patient. On day 15 HCV RNA was undetectable (<15 IU/mL) in 6/9 (67%), 4/8 (50%) and 8/8 (100%) patients in Cohorts 1, 2 and 3 respectively. When co-administered with low dose ritonavir, danoprevir concentrations reached steady state between 6 to 10 days of dosing. Danoprevir exposures increased more than dose proportionally between 100/100 mg and 200/100 mg. Danoprevir/r plus peginterferon alfa-2a (40KD)/ribavirin was well-tolerated with no safety-related discontinuations.
CONCLUSIONS: Danoprevir/r plus peginterferon alfa-2a (40KD)/ribavirin provides profound and robust reductions in serum HCV RNA, at substantially lower systemic exposures compared to those observed with higher doses of danoprevir in the absence of ritonavir. These results support further studies of danoprevir/r.
Copyright © 2011. Published by Elsevier B.V.
Source
Usefulness of viral kinetics for early prediction of a sustained virological response in HCV-1 non-responders re-treated with pegylated interferon and ribavirin
J Hepatol. 2011 Feb 24. [Epub ahead of print]
Deltenre P, Corouge M, Canva V, Castel H, Wartel F, Dharancy S, Louvet A, Lazrek M, Moreno C, Henrion J, Mathurin P.
Service d'Hépato-Gastroentérologie, HÎpital Huriez, CHRU Lille, Lille, France; Service d'Hépato-Gastroentérologie, HÎpital de Jolimont, Haine-Saint-Paul, Belgium.
Abstract
INTRODUCTION: Undetectable HCV RNA at 12 weeks is the stopping rule recommended in HCV patients in whom previous treatment has failed. Whether earlier virological criteria may be useful for deciding treatment discontinuation remains subjects to debate.
AIM: To identify, in HCV-1 non-responders and relapsers to IFN or Peg-IFN and ribavirin, the earliest and most accurate predictor of failure to respond to a new treatment combining Peg-IFN and ribavirin.
METHODS: Prediction of SVR was assessed using the area under the ROC (AUROC) curve of reduction in viral load at different time points.
RESULTS: This study included 151 patients (32% with extensive fibrosis or cirrhosis). A SVR was reached in 34% (21% in non-responders and 59% in relapsers). In non-responders, 1 month was the most accurate time point for predicting SVR (AUROC: 0.787±0.075, p=0.0001). Thirty-seven percent of non-responders did not have a 1-log drop in viral load at 1 month. All these patients had detectable HCV RNA at 3 months (p<0.0001) and only 4% attained a SVR (p=0.004). The same high negative predictive value for SVR was found in sensitivity analysis restricted to non-responders to Peg-IFN and ribavirin. In contrast, in relapsers, undetectable HCV RNA at 3 months was the earliest criterion with high negative predictive value (92%, p<0.0001).
CONCLUSION: All HCV-1 non-responders who did not have a 1-log drop in viral load at 1 month remained HCV-RNA-detectable at 3 months, and only 4% attained a SVR. This new criterion can be used early on as a first stopping rule.
Copyright © 2011. Published by Elsevier B.V.
PMID: 21354445 [PubMed - as supplied by publisher]
Source
Deltenre P, Corouge M, Canva V, Castel H, Wartel F, Dharancy S, Louvet A, Lazrek M, Moreno C, Henrion J, Mathurin P.
Service d'Hépato-Gastroentérologie, HÎpital Huriez, CHRU Lille, Lille, France; Service d'Hépato-Gastroentérologie, HÎpital de Jolimont, Haine-Saint-Paul, Belgium.
Abstract
INTRODUCTION: Undetectable HCV RNA at 12 weeks is the stopping rule recommended in HCV patients in whom previous treatment has failed. Whether earlier virological criteria may be useful for deciding treatment discontinuation remains subjects to debate.
AIM: To identify, in HCV-1 non-responders and relapsers to IFN or Peg-IFN and ribavirin, the earliest and most accurate predictor of failure to respond to a new treatment combining Peg-IFN and ribavirin.
METHODS: Prediction of SVR was assessed using the area under the ROC (AUROC) curve of reduction in viral load at different time points.
RESULTS: This study included 151 patients (32% with extensive fibrosis or cirrhosis). A SVR was reached in 34% (21% in non-responders and 59% in relapsers). In non-responders, 1 month was the most accurate time point for predicting SVR (AUROC: 0.787±0.075, p=0.0001). Thirty-seven percent of non-responders did not have a 1-log drop in viral load at 1 month. All these patients had detectable HCV RNA at 3 months (p<0.0001) and only 4% attained a SVR (p=0.004). The same high negative predictive value for SVR was found in sensitivity analysis restricted to non-responders to Peg-IFN and ribavirin. In contrast, in relapsers, undetectable HCV RNA at 3 months was the earliest criterion with high negative predictive value (92%, p<0.0001).
CONCLUSION: All HCV-1 non-responders who did not have a 1-log drop in viral load at 1 month remained HCV-RNA-detectable at 3 months, and only 4% attained a SVR. This new criterion can be used early on as a first stopping rule.
Copyright © 2011. Published by Elsevier B.V.
PMID: 21354445 [PubMed - as supplied by publisher]
Source
IL28B polymorphisms predict reduction of HCV RNA from the first day of therapy in chronic hepatitis C
J Hepatol. 2011 Feb 24. [Epub ahead of print]
Bochud PY, Bibert S, Negro F, Haagmans B, Soulier A, Ferrari C, Missale G, Zeuzem S, Pawlotsky JM, Schalm S, Hellstrand K, Neumann AU, Lagging M; the DITTO-HCV study group.
Service of Infectious Diseases, Department of Medicine, University Hospital and University of Lausanne, Switzerland.
Abstract
BACKGROUND: Single nucleotide polymorphisms (SNPs) associated with IL28B influence the outcome of peginterferon-α/ribavirin therapy of chronic hepatitis C virus (HCV) infection. We analyzed the kinetics of HCV RNA during therapy as a function of IL28B SNPs.
METHODS: IL28B SNPs rs8099917, rs12979860, and rs12980275 were genotyped in 242 HCV treatment-naĂŻve Caucasian patients (67% genotype 1, 28% genotype 2 or 3) receiving peginterferon-α2a (180 ÎŒg weekly) and ribavirin (1000-1200 mg daily) with serial HCV-RNA quantifications. Associations between IL28B polymorphisms and early viral kinetics were assessed, accounting for relevant covariates.
RESULTS: In the multivariate analyses for genotype 1 patients, the T allele of rs12979860 (T(rs12979860)) was an independent risk factor for a less pronounced first phase HCV RNA decline (log(10) 0.89 IU/ml among T carriers vs. 2.06 among others, adjusted P<0.001) and lower rapid (15% vs. 38%, adjusted P=0.007) and sustained viral response rates (48% versus 66%, adjusted P<0.001). In univariate analyses, T(rs12979860) was also associated with a reduced second phase decline (P=0.002), but this association was no longer significant after adjustment for the first phase decline (adjusted P=0.8). In genotype 2/3 patients, T(rs12979860) was associated with a reduced first phase decline (adjusted P=0.04), but not with second phase decline.
CONCLUSION: Polymorphisms in IL28B are strongly associated with the first phase viral decline during peginterferon-α/ribavirin therapy of chronic HCV infection, irrespective of HCV genotype.
Copyright © 2011. Published by Elsevier B.V.
PMID: 21354446 [PubMed - as supplied by publisher]
Source
Bochud PY, Bibert S, Negro F, Haagmans B, Soulier A, Ferrari C, Missale G, Zeuzem S, Pawlotsky JM, Schalm S, Hellstrand K, Neumann AU, Lagging M; the DITTO-HCV study group.
Service of Infectious Diseases, Department of Medicine, University Hospital and University of Lausanne, Switzerland.
Abstract
BACKGROUND: Single nucleotide polymorphisms (SNPs) associated with IL28B influence the outcome of peginterferon-α/ribavirin therapy of chronic hepatitis C virus (HCV) infection. We analyzed the kinetics of HCV RNA during therapy as a function of IL28B SNPs.
METHODS: IL28B SNPs rs8099917, rs12979860, and rs12980275 were genotyped in 242 HCV treatment-naĂŻve Caucasian patients (67% genotype 1, 28% genotype 2 or 3) receiving peginterferon-α2a (180 ÎŒg weekly) and ribavirin (1000-1200 mg daily) with serial HCV-RNA quantifications. Associations between IL28B polymorphisms and early viral kinetics were assessed, accounting for relevant covariates.
RESULTS: In the multivariate analyses for genotype 1 patients, the T allele of rs12979860 (T(rs12979860)) was an independent risk factor for a less pronounced first phase HCV RNA decline (log(10) 0.89 IU/ml among T carriers vs. 2.06 among others, adjusted P<0.001) and lower rapid (15% vs. 38%, adjusted P=0.007) and sustained viral response rates (48% versus 66%, adjusted P<0.001). In univariate analyses, T(rs12979860) was also associated with a reduced second phase decline (P=0.002), but this association was no longer significant after adjustment for the first phase decline (adjusted P=0.8). In genotype 2/3 patients, T(rs12979860) was associated with a reduced first phase decline (adjusted P=0.04), but not with second phase decline.
CONCLUSION: Polymorphisms in IL28B are strongly associated with the first phase viral decline during peginterferon-α/ribavirin therapy of chronic HCV infection, irrespective of HCV genotype.
Copyright © 2011. Published by Elsevier B.V.
PMID: 21354446 [PubMed - as supplied by publisher]
Source
Pharmasset Hep C Data Wows Investors
By Adam Feuerstein 03/08/11 - 11:46 AM EST
PRINCETON, N.J. (TheStreet) -- Pharmasset(VRUS_) shares are soaring on the release of new but very preliminary data that hints at a breakthrough, all-oral cure for hepatitis C.
Treatment with two oral drugs developed by Pharmasset resulted in 15 of 16, or 94%, of patients reporting undetectable levels of the hepatitis C virus after 14 days, according to interim results from a study released Monday.
These early data on the two Pharmasset drugs -- PSI-938 and PSI-7977 are the best reported to date by any company seeking to develop a new, all-oral therapy for hepatitis C. This Pharmasset effort is drawing even more attention because it potentially eliminates the need for patients to be treated with long-acting interferon, one of two drugs currently used to treat hepatitis C but which is difficult for patients to tolerate and causes many side effects.
Pharmasset shares rose 24% on Monday and were up another 8% to $66.92 on Tuesday.
The PSI-938 and PSI-7977 combination data were released Monday in a research abstract released online by the European Association for the Study of the Liver (EASL), which holds its annual meeting March 30 through April 3.
EASL makes research abstracts for its annual meeting freely available to the public but prohibits journalists from writing about the data contained in the research abstracts until they are presented at the annual meeting. TheStreet refuses to adhere to EASL's media embargo since these hepatitis C data are freely available online now and are impacting the stock prices of publicly traded companies developing hepatitis C drugs.
While investors are displaying great enthusiasm for the Pharmasset all-oral drug combination, the data from the study are very early. One particular risk seen in other, similar studies that omit long-acting interferon is the development of mutated hepatitis C virus that can quickly become resistant to drug treatment.
None of the patients treated in the Pharmasset study have reported rebounding levels of hepatitis C virus, according to the research abstract, but so-called viral rebound may emerge as patients are treated longer, or when treatment is stopped and these patients are followed long-term to determine if they are truly cured.
Source
PRINCETON, N.J. (TheStreet) -- Pharmasset(VRUS_) shares are soaring on the release of new but very preliminary data that hints at a breakthrough, all-oral cure for hepatitis C.
Treatment with two oral drugs developed by Pharmasset resulted in 15 of 16, or 94%, of patients reporting undetectable levels of the hepatitis C virus after 14 days, according to interim results from a study released Monday.
These early data on the two Pharmasset drugs -- PSI-938 and PSI-7977 are the best reported to date by any company seeking to develop a new, all-oral therapy for hepatitis C. This Pharmasset effort is drawing even more attention because it potentially eliminates the need for patients to be treated with long-acting interferon, one of two drugs currently used to treat hepatitis C but which is difficult for patients to tolerate and causes many side effects.
Pharmasset shares rose 24% on Monday and were up another 8% to $66.92 on Tuesday.
The PSI-938 and PSI-7977 combination data were released Monday in a research abstract released online by the European Association for the Study of the Liver (EASL), which holds its annual meeting March 30 through April 3.
EASL makes research abstracts for its annual meeting freely available to the public but prohibits journalists from writing about the data contained in the research abstracts until they are presented at the annual meeting. TheStreet refuses to adhere to EASL's media embargo since these hepatitis C data are freely available online now and are impacting the stock prices of publicly traded companies developing hepatitis C drugs.
While investors are displaying great enthusiasm for the Pharmasset all-oral drug combination, the data from the study are very early. One particular risk seen in other, similar studies that omit long-acting interferon is the development of mutated hepatitis C virus that can quickly become resistant to drug treatment.
None of the patients treated in the Pharmasset study have reported rebounding levels of hepatitis C virus, according to the research abstract, but so-called viral rebound may emerge as patients are treated longer, or when treatment is stopped and these patients are followed long-term to determine if they are truly cured.
Source
Subset of HIV/HCV Co-infected at Risk for Hepatic Steatosis
By: MARY ANN MOON, Internal Medicine News Digital Network
03/01/11
In patients co-infected with HIV and hepatitis C virus, alcohol use and a high body mass index are associated with progression of hepatic steatosis, whereas exposure to certain antiretrovirals and a high baseline CD4 count appear to be protective against steatosis, Dr. Tinsay A. Woreta and her colleagues reported in the March issue of Gastroenterology.
In their study of 222 patients who were co-infected with HIV and HCV, more than 90% showed no progression of steatosis during nearly 3 years of follow-up.
The findings indicate that efforts to diagnose and prevent hepatic steatosis "should be focused on persons with a high body mass index and excessive alcohol intake," said Dr. Woreta of Johns Hopkins University, Baltimore, and her associates (Gastroenterology 2011 March [doi:10.1053/j.gastro.2010.11.052]).
Hepatitis C virus is not uncommon in patients with HIV infection, and hepatic steatosis affects 30%-70% of those with both infections. The steatosis is associated with hepatic fibrosis and is thought to contribute to the more rapid progression of liver disease in co-infected patients than in those who don’t have concomitant HIV.
"The natural history of hepatic steatosis is incompletely understood" because most studies have been cross-sectional rather than longitudinal," wrote Dr. Woreta and her colleagues. They performed their longitudinal study to prospectively examine the natural history of steatosis, using data from HIV/HCV–co-infected patients who underwent serial liver biopsies while attending an urban HIV clinic.
There were 345 pairs of serial biopsies available for analysis. The study subjects had a median age of 44 years; 66% were men and 87% were black. Nearly half were overweight or obese. Almost all (94%) had HCV genotype 1.
Most patients (194, or 87%) had no or only trivial hepatic steatosis at baseline, and it did not progress during follow-up in 165 (74%) of them. The other 29 patients who had no or only trivial hepatic steatosis at baseline progressed to significant steatosis during follow-up.
In all, 28 patients had significant hepatic steatosis at baseline, and the steatosis actually regressed in 21 (75%) of them. The other seven patients who had significant hepatic steatosis at baseline maintained that steatosis.
Persistence or progression of steatosis was strongly associated with a history of alcohol abuse. Although few patients reported current alcohol abuse, the medical records showed chronic alcoholism or abuse in approximately half. Many study subjects were probably underreporting their current exposure, particularly because they were aware that they were participating in a study of liver outcomes. "Clinicians evaluating fatty liver disease in HIV-infected patients should remain cognizant about the likelihood of underreporting of alcohol consumption," the investigators noted.
Obesity also was strongly associated with persistent or progressive steatosis, which was not unexpected. Although HIV infection was, until a short time ago, "a progressively fatal disease characterized by severe wasting, the advent of HAART [highly active antiretroviral therapy] has transformed HIV into a chronic disease with an increase in the prevalence of obesity."
"These data underscore the importance of measures to prevent and treat obesity in HIV/HCV–co-infected patients, [given] the development or worsening of hepatic steatosis in these patients," the researchers said.
Longer exposure to antiretroviral therapy appeared to be protective against persistent or progressive steatosis. One possible mechanism for this finding is that HIV infection may promote steatosis by facilitating HCV replication in hepatocytes, so reducing the HIV load would ease steatosis.
"Another possibility is that HIV acts synergistically with HCV to disrupt lipid metabolism. Thus, direct inhibition of HIV viral replication could decrease steatosis, particularly if the antiretroviral agent [has] minimal impact on mitochondrial replication and function," Dr. Woreta and her colleagues said.
They emphasized that stavudine, which has been designated as a "nonpreferred" antiretroviral agent because it was thought to contribute to steatosis, was used by only 6% of patients in this study, so the authors were unable to assess its effects.
A higher CD4 cell count at baseline also appeared to be protective against steatosis. The investigators did not offer any possible explanations for this effect. No association was found between steatosis progression and patient age, sex, race, diabetes status, HCV genotype, fibrosis status, or HCV therapy, they noted.
This study was supported by the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, the National Center for Complementary and Alternative Medicine, the Agency for Healthcare Policy and Research, and the clinical research unit at the Johns Hopkins Medical Institutions. The investigators reported that they had no financial conflicts of interest.
Source
03/01/11
In patients co-infected with HIV and hepatitis C virus, alcohol use and a high body mass index are associated with progression of hepatic steatosis, whereas exposure to certain antiretrovirals and a high baseline CD4 count appear to be protective against steatosis, Dr. Tinsay A. Woreta and her colleagues reported in the March issue of Gastroenterology.
In their study of 222 patients who were co-infected with HIV and HCV, more than 90% showed no progression of steatosis during nearly 3 years of follow-up.
The findings indicate that efforts to diagnose and prevent hepatic steatosis "should be focused on persons with a high body mass index and excessive alcohol intake," said Dr. Woreta of Johns Hopkins University, Baltimore, and her associates (Gastroenterology 2011 March [doi:10.1053/j.gastro.2010.11.052]).
Hepatitis C virus is not uncommon in patients with HIV infection, and hepatic steatosis affects 30%-70% of those with both infections. The steatosis is associated with hepatic fibrosis and is thought to contribute to the more rapid progression of liver disease in co-infected patients than in those who don’t have concomitant HIV.
"The natural history of hepatic steatosis is incompletely understood" because most studies have been cross-sectional rather than longitudinal," wrote Dr. Woreta and her colleagues. They performed their longitudinal study to prospectively examine the natural history of steatosis, using data from HIV/HCV–co-infected patients who underwent serial liver biopsies while attending an urban HIV clinic.
There were 345 pairs of serial biopsies available for analysis. The study subjects had a median age of 44 years; 66% were men and 87% were black. Nearly half were overweight or obese. Almost all (94%) had HCV genotype 1.
Most patients (194, or 87%) had no or only trivial hepatic steatosis at baseline, and it did not progress during follow-up in 165 (74%) of them. The other 29 patients who had no or only trivial hepatic steatosis at baseline progressed to significant steatosis during follow-up.
In all, 28 patients had significant hepatic steatosis at baseline, and the steatosis actually regressed in 21 (75%) of them. The other seven patients who had significant hepatic steatosis at baseline maintained that steatosis.
Persistence or progression of steatosis was strongly associated with a history of alcohol abuse. Although few patients reported current alcohol abuse, the medical records showed chronic alcoholism or abuse in approximately half. Many study subjects were probably underreporting their current exposure, particularly because they were aware that they were participating in a study of liver outcomes. "Clinicians evaluating fatty liver disease in HIV-infected patients should remain cognizant about the likelihood of underreporting of alcohol consumption," the investigators noted.
Obesity also was strongly associated with persistent or progressive steatosis, which was not unexpected. Although HIV infection was, until a short time ago, "a progressively fatal disease characterized by severe wasting, the advent of HAART [highly active antiretroviral therapy] has transformed HIV into a chronic disease with an increase in the prevalence of obesity."
"These data underscore the importance of measures to prevent and treat obesity in HIV/HCV–co-infected patients, [given] the development or worsening of hepatic steatosis in these patients," the researchers said.
Longer exposure to antiretroviral therapy appeared to be protective against persistent or progressive steatosis. One possible mechanism for this finding is that HIV infection may promote steatosis by facilitating HCV replication in hepatocytes, so reducing the HIV load would ease steatosis.
"Another possibility is that HIV acts synergistically with HCV to disrupt lipid metabolism. Thus, direct inhibition of HIV viral replication could decrease steatosis, particularly if the antiretroviral agent [has] minimal impact on mitochondrial replication and function," Dr. Woreta and her colleagues said.
They emphasized that stavudine, which has been designated as a "nonpreferred" antiretroviral agent because it was thought to contribute to steatosis, was used by only 6% of patients in this study, so the authors were unable to assess its effects.
A higher CD4 cell count at baseline also appeared to be protective against steatosis. The investigators did not offer any possible explanations for this effect. No association was found between steatosis progression and patient age, sex, race, diabetes status, HCV genotype, fibrosis status, or HCV therapy, they noted.
This study was supported by the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, the National Center for Complementary and Alternative Medicine, the Agency for Healthcare Policy and Research, and the clinical research unit at the Johns Hopkins Medical Institutions. The investigators reported that they had no financial conflicts of interest.
Source
IL28B gene predicts treatment outcome for liver transplantation patients
Public release date: 2-Mar-2011
Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell
Genetic variants determine severity of HCV-related graft disease and antiviral treatment response
German researchers have found a significant association of IL28B genotypes to interferon-based antiviral treatment outcome, and to graft inflammation caused by hepatitis C virus (HCV). The study determined that the presence of G-allele serves as a marker for severe HCV-induced graft inflammation, as well as a predictor for unsuccessful treatment. Study findings—the largest to report on the role IL28B variants in a transplant cohort with recurrent HCV—are published in the March issue of Liver Transplantation, a journal of the American Association for the Study of Liver Diseases.
The IL28B gene encodes interferons (IFNs), which are proteins made by lymphocytes to motivate the immune system in the presence of pathogens. IFN-α proteins are produced by leukocytes and are prevalent in the presence of a viral infection such as HCV. Researchers determined the prevalence of IL28B genotypes (GG, GT, TT) in 183 liver transplant patients, analyzing 605 protocol liver biopsies performed six months to ten or more years after transplantation.
The authors determined that the presence of G-allele was a marker for more severe graft inflammation and was observed to have a strong association to antiviral treatment failure in 103 of 159 patients. T-allele was more frequent among patients with lower inflammation grades, concluding a definite association between IL28B G-allele and HCV-induced graft inflammation, and the G-allele as a predictor of unsuccessful antiviral treatment. The team also found that IL28B genotypes did not seem to affect median fibrosis.
"Successful liver transplantation creates a unique population of quasi-normal individuals relying on a harmonic interaction of two different genetic backgrounds," said Dennis Eurich, MD, from the Department of General, Visceral and Transplant Surgery at Charité, Campus Virchow in Berlin and lead author of the current study. "IL28B polymorphisms may help to identify patients at risk for developing more severe graft hepatitis. These genetic variants might help to individually predict potential response to antiviral therapy, enabling medical professionals to appropriately adapt treatment."
A related editorial also published in Liver Transplantation this month acknowledges the association between IL28B polymorphisms and HCV-induced graft inflammation, and the prediction of treatment outcomes. Geoffrey McCaughan from the Centenary Institute in Australia said, "The exact mechanisms of how this association results in higher sustained virologic response rates remain unclear, however the data has invigorated research into both prediction of treatment outcomes and the mechanisms of control of HCV replication and clearance."
Infection with HCV is the primary cause of cirrhosis of the liver and liver cancer worldwide. Up to 30% of liver transplants will develop graft cirrhosis within five years after liver transplantation due to recurrent HCV-infection. HCV-induced graft fibrosis is the main determinant of morbidity and mortality of liver transplant patients.
###
These studies are published in Liver Transplantation. Media wishing to receive a PDF of this article may contact healthnews@wiley.com.
Full citation: "Relationship between IL-28b Gene Polymorphism and Histological Severity of HCV-Induced Graft Inflammation and Response to Antiviral Therapy after Liver Transplantation." Dennis Eurich, Sabine Boas-Knoop, Martin Ruehl, M. Schulz, Esperanza Carrillo, Thomas Berg, Ruth Neuhaus, Peter Neuhaus, Ulf Neumann, and Marcus Bahra. Liver Transplantation; Published Online: December 6, 2011 (DOI: 10.1002/lt.22235) Print Issue Date: March 2011. http://onlinelibrary.wiley.com/doi/10.1002/lt.22235/abstract.
Editorial: "Liver Transplantation in Hepatitis C; Will Understanding the IL28B Polymorphisms Improve Outcomes?" Geoffrey McCaughan, Nicholas Shackel, and David Bowen. Liver Transplantation; Published Online: January 14, 2011 (DOI: 10.1002/lt.22252); Print Issue Date: March 2011. http://onlinelibrary.wiley.com/doi/10.1002/lt.22252/abstract.
About the Journal
Liver Transplantation is published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society . Since the first application of liver transplantation in a clinical situation was reported more than twenty years ago, there has been a great deal of growth in this field and more is anticipated. As an official publication of the AALSD and the ILTS, Liver Transplantation delivers current, peer-reviewed articles on surgical techniques, clinical investigations and drug research — the information necessary to keep abreast of this evolving specialty.
About Wiley-Blackwell
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/ or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.
Source
Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell
Genetic variants determine severity of HCV-related graft disease and antiviral treatment response
German researchers have found a significant association of IL28B genotypes to interferon-based antiviral treatment outcome, and to graft inflammation caused by hepatitis C virus (HCV). The study determined that the presence of G-allele serves as a marker for severe HCV-induced graft inflammation, as well as a predictor for unsuccessful treatment. Study findings—the largest to report on the role IL28B variants in a transplant cohort with recurrent HCV—are published in the March issue of Liver Transplantation, a journal of the American Association for the Study of Liver Diseases.
The IL28B gene encodes interferons (IFNs), which are proteins made by lymphocytes to motivate the immune system in the presence of pathogens. IFN-α proteins are produced by leukocytes and are prevalent in the presence of a viral infection such as HCV. Researchers determined the prevalence of IL28B genotypes (GG, GT, TT) in 183 liver transplant patients, analyzing 605 protocol liver biopsies performed six months to ten or more years after transplantation.
The authors determined that the presence of G-allele was a marker for more severe graft inflammation and was observed to have a strong association to antiviral treatment failure in 103 of 159 patients. T-allele was more frequent among patients with lower inflammation grades, concluding a definite association between IL28B G-allele and HCV-induced graft inflammation, and the G-allele as a predictor of unsuccessful antiviral treatment. The team also found that IL28B genotypes did not seem to affect median fibrosis.
"Successful liver transplantation creates a unique population of quasi-normal individuals relying on a harmonic interaction of two different genetic backgrounds," said Dennis Eurich, MD, from the Department of General, Visceral and Transplant Surgery at Charité, Campus Virchow in Berlin and lead author of the current study. "IL28B polymorphisms may help to identify patients at risk for developing more severe graft hepatitis. These genetic variants might help to individually predict potential response to antiviral therapy, enabling medical professionals to appropriately adapt treatment."
A related editorial also published in Liver Transplantation this month acknowledges the association between IL28B polymorphisms and HCV-induced graft inflammation, and the prediction of treatment outcomes. Geoffrey McCaughan from the Centenary Institute in Australia said, "The exact mechanisms of how this association results in higher sustained virologic response rates remain unclear, however the data has invigorated research into both prediction of treatment outcomes and the mechanisms of control of HCV replication and clearance."
Infection with HCV is the primary cause of cirrhosis of the liver and liver cancer worldwide. Up to 30% of liver transplants will develop graft cirrhosis within five years after liver transplantation due to recurrent HCV-infection. HCV-induced graft fibrosis is the main determinant of morbidity and mortality of liver transplant patients.
###
These studies are published in Liver Transplantation. Media wishing to receive a PDF of this article may contact healthnews@wiley.com.
Full citation: "Relationship between IL-28b Gene Polymorphism and Histological Severity of HCV-Induced Graft Inflammation and Response to Antiviral Therapy after Liver Transplantation." Dennis Eurich, Sabine Boas-Knoop, Martin Ruehl, M. Schulz, Esperanza Carrillo, Thomas Berg, Ruth Neuhaus, Peter Neuhaus, Ulf Neumann, and Marcus Bahra. Liver Transplantation; Published Online: December 6, 2011 (DOI: 10.1002/lt.22235) Print Issue Date: March 2011. http://onlinelibrary.wiley.com/doi/10.1002/lt.22235/abstract.
Editorial: "Liver Transplantation in Hepatitis C; Will Understanding the IL28B Polymorphisms Improve Outcomes?" Geoffrey McCaughan, Nicholas Shackel, and David Bowen. Liver Transplantation; Published Online: January 14, 2011 (DOI: 10.1002/lt.22252); Print Issue Date: March 2011. http://onlinelibrary.wiley.com/doi/10.1002/lt.22252/abstract.
About the Journal
Liver Transplantation is published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society . Since the first application of liver transplantation in a clinical situation was reported more than twenty years ago, there has been a great deal of growth in this field and more is anticipated. As an official publication of the AALSD and the ILTS, Liver Transplantation delivers current, peer-reviewed articles on surgical techniques, clinical investigations and drug research — the information necessary to keep abreast of this evolving specialty.
About Wiley-Blackwell
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com/ or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.
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Study: Osteoporosis is more common among patients with HIV and hepatitis C
Previous studies have already established that individuals with HIV are more likely to suffer from osteoporosis. Now, the latest research has found a corollary to this effect. According to a new investigation, HIV-positive patients who have hepatitis C have even higher rates of osteoporosis than those without the liver disease.
The findings, which were published in the Journal of Hepatology, pointed to the need for increased vigilance for bone loss among people co-infected with HIV and hepatitis C.
The National Institutes of Health estimates that osteoporosis is already four times more likely among people with HIV than among those without the disease.
HIV and hepatitis C are both incurable diseases, though each may be brought under control with medical treatments and prescription medications.
Approximately 20,000 new cases of hepatitis C - a chronic liver disorder that causes inflammation scarring and even failure of the organ - occur every year in the U.S., according to the Centers for Disease Control and Prevention.
By contrast, new HIV infections are nearly three times as prevalent. The agency reports that more than 56,000 new cases of HIV are contracted annually.
In the new study, scientists analyzed the bone mineral density of around 180 patients who had tested positive for both HIV and hepatitis C. Around 28 percent of the participants, most of whom were middle-aged African-Americans, tested positive for osteoporosis.
Bone density scans found that these patients were most likely to have low bone mass in the spine, followed by the hip and leg.
In contrast to these results, the study's authors said that previously gathered data indicate that people infected solely with HIV have between a 15 and 20 percent chance of having osteoporosis.
The team concluded that while further research into the interactions between HIV, hepatitis C and bone tissue is merited, physicians should strongly consider testing all patients with HIV or hepatitis for decreased bone density.
More than 10 million Americans have osteoporosis and another 34 million are at risk for it, according to the National Osteoporosis Foundation.
Source
The findings, which were published in the Journal of Hepatology, pointed to the need for increased vigilance for bone loss among people co-infected with HIV and hepatitis C.
The National Institutes of Health estimates that osteoporosis is already four times more likely among people with HIV than among those without the disease.
HIV and hepatitis C are both incurable diseases, though each may be brought under control with medical treatments and prescription medications.
Approximately 20,000 new cases of hepatitis C - a chronic liver disorder that causes inflammation scarring and even failure of the organ - occur every year in the U.S., according to the Centers for Disease Control and Prevention.
By contrast, new HIV infections are nearly three times as prevalent. The agency reports that more than 56,000 new cases of HIV are contracted annually.
In the new study, scientists analyzed the bone mineral density of around 180 patients who had tested positive for both HIV and hepatitis C. Around 28 percent of the participants, most of whom were middle-aged African-Americans, tested positive for osteoporosis.
Bone density scans found that these patients were most likely to have low bone mass in the spine, followed by the hip and leg.
In contrast to these results, the study's authors said that previously gathered data indicate that people infected solely with HIV have between a 15 and 20 percent chance of having osteoporosis.
The team concluded that while further research into the interactions between HIV, hepatitis C and bone tissue is merited, physicians should strongly consider testing all patients with HIV or hepatitis for decreased bone density.
More than 10 million Americans have osteoporosis and another 34 million are at risk for it, according to the National Osteoporosis Foundation.
Source
Idenix Announces Data Presentations at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL)
CAMBRIDGE, Mass., March 7, 2011 /PRNewswire/ -- Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced that two abstracts have been accepted for presentation at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL, March 30- April 3, 2011 in Berlin, Germany). Full abstracts can now be viewed at the EASL website at http://www.easl.eu/.
The accepted abstracts are as follows:
• Standring, et al, "Idenix NS5A HCV Replication Inhibitors with Low Picomolar, Pan-Genotypic in vitro Antiviral Activity" will be presented in a poster session beginning on Friday, April 1.
• Standring, et al, "No Resistance to IDX184 Was Detected in 3-day and 14-day Clinical Studies of IDX184 in Genotype 1-Infected HCV Subjects" will be presented in a poster session on Saturday, April 2.
About Idenix
Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of infections caused by hepatitis C virus. For further information about Idenix, please refer to http://www.idenix.com/.
Forward-looking Statements
This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the company's future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the company's potential pipeline candidates, including any expressed or implied statements regarding the efficacy and safety of our drug candidates, the likelihood and success of any future clinical trials involving our drug candidates. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; the company's ability to obtain additional funding required to conduct its research, development and commercialization activities; the company's dependence on its collaborations with Novartis Pharma AG and GlaxoSmithKline/ViiV Healthcare; changes in the company's business plan or objectives; the ability of the company to attract and retain qualified personnel; competition in general; and the company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the company's annual report on Form 10-K for the year ended December 31, 2010, as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the company files with the SEC.
All forward-looking statements reflect the company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the company's estimates change.
Idenix Pharmaceuticals Contact:
Kelly Barry (617) 995-9033 (media)
Eric Hoffman (617) 224-4485 (investors)
SOURCE Idenix Pharmaceuticals, Inc.
RELATED LINKS
http://www.idenix.com/
Source
The accepted abstracts are as follows:
• Standring, et al, "Idenix NS5A HCV Replication Inhibitors with Low Picomolar, Pan-Genotypic in vitro Antiviral Activity" will be presented in a poster session beginning on Friday, April 1.
• Standring, et al, "No Resistance to IDX184 Was Detected in 3-day and 14-day Clinical Studies of IDX184 in Genotype 1-Infected HCV Subjects" will be presented in a poster session on Saturday, April 2.
About Idenix
Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of infections caused by hepatitis C virus. For further information about Idenix, please refer to http://www.idenix.com/.
Forward-looking Statements
This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the company's future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the company's potential pipeline candidates, including any expressed or implied statements regarding the efficacy and safety of our drug candidates, the likelihood and success of any future clinical trials involving our drug candidates. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; the company's ability to obtain additional funding required to conduct its research, development and commercialization activities; the company's dependence on its collaborations with Novartis Pharma AG and GlaxoSmithKline/ViiV Healthcare; changes in the company's business plan or objectives; the ability of the company to attract and retain qualified personnel; competition in general; and the company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the company's annual report on Form 10-K for the year ended December 31, 2010, as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the company files with the SEC.
All forward-looking statements reflect the company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the company's estimates change.
Idenix Pharmaceuticals Contact:
Kelly Barry (617) 995-9033 (media)
Eric Hoffman (617) 224-4485 (investors)
SOURCE Idenix Pharmaceuticals, Inc.
RELATED LINKS
http://www.idenix.com/
Source
Idera Pharmaceuticals Announces IMO-2125 Data Presentation at the 46th Annual Meeting of the European Association for the Study of the Liver
March 08, 2011 08:00 AM Eastern Time
2011 Meeting of the European Association for the Study of the Liver
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) today announced that data from its Phase 1 clinical trial of IMO-2125, its novel immune modulator for the treatment of chronic hepatitis C virus (HCV) infection, in treatment-naĂŻve genotype 1 HCV patients will be presented at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) being held March 30 – April 3, 2011 in Berlin, Germany. The presentation entitled "IMO-2125 plus ribavirin gives substantial first-dose viral load reductions, cumulative antiviral effect, is well tolerated in naĂŻve genotype 1 HCV patients: a Phase 1 trial,” D. Guyader, et al., will be made in a poster session entitled Viral Hepatitis C: Clinical (new compounds, resistance) on Saturday, April 2, 2011. The full abstract (#1209) can now be accessed through the EASL website http://www.easl.eu/.
About IMO-2125
IMO-2125, a Toll-like Receptor (TLR) 9 agonist, is a novel immune modulator being developed as a component of treatment for chronic hepatitis C virus (HCV) infection. IMO-2125 is designed to stimulate the immune system, causing the body to generate natural interferons and other antiviral cytokines. IMO-2125 has been evaluated in a Phase 1 clinical trial in null-responder HCV patients, defined as those who did not achieve a 2 log10 reduction with prior standard of care treatment, as monotherapy for 4 weeks and in a Phase 1 clinical trial in treatment-naĂŻve HCV patients in combination with ribavirin for 4 weeks.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals develops drug candidates to treat chronic hepatitis C virus infection, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. The company's proprietary drug candidates are designed to modulate specific Toll-like Receptors, which are a family of immune system receptors. Idera's pioneering DNA and RNA chemistry expertise enables it to create drug candidates for internal development and generates opportunities for multiple collaborative alliances. For more information, visit http://www.iderapharma.com/.
Idera Forward Looking Statements
This press release contains forward-looking statements concerning Idera Pharmaceuticals, Inc. that involve a number of risks and uncertainties. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words "believes," "anticipates," "plans," "expects," "estimates," "intends," "should," "could," "will," "may," and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause Idera's actual results to differ materially from those indicated by such forward-looking statements; whether results obtained in preclinical and clinical studies such as the studies referred to in this release will be indicative of results obtained in future clinical trials; whether products based on Idera's technology will advance into or through the clinical trial process on a timely basis or at all and receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether, if the Company's products receive approval, they will be successfully distributed and marketed; whether the Company's collaborations will be successful; whether the patents and patent applications owned or licensed by the Company will protect the Company’s technology and prevent others from infringing it; whether Idera's cash resources will be sufficient to fund the Company's operations; and such other important factors as are set forth under the caption "Risk Factors" in Idera's Quarterly Report on Form 10-Q for the three months ended September 30, 2010, which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.
Contacts
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
cerdman@macbiocom.com
Source
2011 Meeting of the European Association for the Study of the Liver
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) today announced that data from its Phase 1 clinical trial of IMO-2125, its novel immune modulator for the treatment of chronic hepatitis C virus (HCV) infection, in treatment-naĂŻve genotype 1 HCV patients will be presented at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) being held March 30 – April 3, 2011 in Berlin, Germany. The presentation entitled "IMO-2125 plus ribavirin gives substantial first-dose viral load reductions, cumulative antiviral effect, is well tolerated in naĂŻve genotype 1 HCV patients: a Phase 1 trial,” D. Guyader, et al., will be made in a poster session entitled Viral Hepatitis C: Clinical (new compounds, resistance) on Saturday, April 2, 2011. The full abstract (#1209) can now be accessed through the EASL website http://www.easl.eu/.
About IMO-2125
IMO-2125, a Toll-like Receptor (TLR) 9 agonist, is a novel immune modulator being developed as a component of treatment for chronic hepatitis C virus (HCV) infection. IMO-2125 is designed to stimulate the immune system, causing the body to generate natural interferons and other antiviral cytokines. IMO-2125 has been evaluated in a Phase 1 clinical trial in null-responder HCV patients, defined as those who did not achieve a 2 log10 reduction with prior standard of care treatment, as monotherapy for 4 weeks and in a Phase 1 clinical trial in treatment-naĂŻve HCV patients in combination with ribavirin for 4 weeks.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals develops drug candidates to treat chronic hepatitis C virus infection, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. The company's proprietary drug candidates are designed to modulate specific Toll-like Receptors, which are a family of immune system receptors. Idera's pioneering DNA and RNA chemistry expertise enables it to create drug candidates for internal development and generates opportunities for multiple collaborative alliances. For more information, visit http://www.iderapharma.com/.
Idera Forward Looking Statements
This press release contains forward-looking statements concerning Idera Pharmaceuticals, Inc. that involve a number of risks and uncertainties. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words "believes," "anticipates," "plans," "expects," "estimates," "intends," "should," "could," "will," "may," and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause Idera's actual results to differ materially from those indicated by such forward-looking statements; whether results obtained in preclinical and clinical studies such as the studies referred to in this release will be indicative of results obtained in future clinical trials; whether products based on Idera's technology will advance into or through the clinical trial process on a timely basis or at all and receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether, if the Company's products receive approval, they will be successfully distributed and marketed; whether the Company's collaborations will be successful; whether the patents and patent applications owned or licensed by the Company will protect the Company’s technology and prevent others from infringing it; whether Idera's cash resources will be sufficient to fund the Company's operations; and such other important factors as are set forth under the caption "Risk Factors" in Idera's Quarterly Report on Form 10-Q for the three months ended September 30, 2010, which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.
Contacts
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
cerdman@macbiocom.com
Source
Pharmasset to Challenge Vertex Hepatitis C Treatment, BMO Says
By Naomi Kresge - Mar 8, 2011 9:57 AM ET
Pharmasset Inc. (VRUS)’s experimental hepatitis C therapies may pose a challenge to treatments from Vertex Pharmaceuticals Inc. (VRTX), based on trial results to be released in late March, BMO Capital Markets Corp. analysts said.
Two drugs from Pharmasset showed “impressive” figures as stand-alone medications or combination therapies, while results from a two-drug combination from Vertex weren’t good enough to justify more patient studies, the analysts, led by Jason Zhang in Montreal, wrote in a research report to investors yesterday, citing abstracts of the trials.
The Vertex trial combined its drug telaprevir, due for U.S. regulatory review on May 23, with experimental drug VX-222, Zhang wrote. The Pharmasset trials combined two experimental therapies, PSI-7977 and PSI-938, with standard therapies or with each other. Zhang lowered his recommendation on Vertex’s stock from “outperform” to “market perform,” saying that investors already expect telaprevir to be approved.
“The hepatitis C treatment landscape subsequent to the initial phase of telaprevir dominance is tilting away from Vertex to companies such as Pharmasset that have potent combinations,” Zhang wrote.
Vertex fell as much as 5.1 percent to $47.07 and was down 5 percent in Nasdaq trading as of 9:53 a.m. in New York. That pared the stock’s gain this year to 35 percent, valuing the Cambridge, Massachusetts-based company at $9.64 billion. Princeton, New Jersey-based Pharmasset jumped as much as 7.3 percent to $66.48 and was up 4 percent.
Telaprevir may generate $1.9 billion in revenue in 2012, according to BMO’s estimates.
The trials were summarized in abstracts released yesterday by the European Association for the Study of the Liver. Though published online, the data are under a press embargo until the conference, which starts on March 30 in Berlin.
To contact the reporter on this story: Naomi Kresge in Berlin at nkresge@bloomberg.net
To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net
Source
Pharmasset Inc. (VRUS)’s experimental hepatitis C therapies may pose a challenge to treatments from Vertex Pharmaceuticals Inc. (VRTX), based on trial results to be released in late March, BMO Capital Markets Corp. analysts said.
Two drugs from Pharmasset showed “impressive” figures as stand-alone medications or combination therapies, while results from a two-drug combination from Vertex weren’t good enough to justify more patient studies, the analysts, led by Jason Zhang in Montreal, wrote in a research report to investors yesterday, citing abstracts of the trials.
The Vertex trial combined its drug telaprevir, due for U.S. regulatory review on May 23, with experimental drug VX-222, Zhang wrote. The Pharmasset trials combined two experimental therapies, PSI-7977 and PSI-938, with standard therapies or with each other. Zhang lowered his recommendation on Vertex’s stock from “outperform” to “market perform,” saying that investors already expect telaprevir to be approved.
“The hepatitis C treatment landscape subsequent to the initial phase of telaprevir dominance is tilting away from Vertex to companies such as Pharmasset that have potent combinations,” Zhang wrote.
Vertex fell as much as 5.1 percent to $47.07 and was down 5 percent in Nasdaq trading as of 9:53 a.m. in New York. That pared the stock’s gain this year to 35 percent, valuing the Cambridge, Massachusetts-based company at $9.64 billion. Princeton, New Jersey-based Pharmasset jumped as much as 7.3 percent to $66.48 and was up 4 percent.
Telaprevir may generate $1.9 billion in revenue in 2012, according to BMO’s estimates.
The trials were summarized in abstracts released yesterday by the European Association for the Study of the Liver. Though published online, the data are under a press embargo until the conference, which starts on March 30 in Berlin.
To contact the reporter on this story: Naomi Kresge in Berlin at nkresge@bloomberg.net
To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net
Source
Gilead Drug Combination Cut Hepatitis Virus in Study, RBC Says
By Kristen Hallam - Mar 8, 2011 7:27 AM ET
Gilead Sciences Inc. (GILD)’s four-drug combination eliminated hepatitis C virus in patients in an early-stage study, RBC Capital Markets LLC analysts said.
The findings support an ongoing mid-stage study of the combination, the analysts, led by Michael Yee in San Francisco, wrote yesterday in a note to investors, citing an abstract of the trial. The analysts said they expect data next year from a mid-stage study by the Foster City, California-based company.
The early-stage study examined a combination of Gilead’s GS-9256 and GS-9190 with two older drugs that are the standard of care, ribavirin and Peg-interferon, according to the note.
The data will be presented at the annual meeting of the European Association for the Study of the Liver starting March 30 in Berlin.
To contact the reporter on this story: Kristen Hallam in London at khallam@bloomberg.net
To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net
Source
Gilead Sciences Inc. (GILD)’s four-drug combination eliminated hepatitis C virus in patients in an early-stage study, RBC Capital Markets LLC analysts said.
The findings support an ongoing mid-stage study of the combination, the analysts, led by Michael Yee in San Francisco, wrote yesterday in a note to investors, citing an abstract of the trial. The analysts said they expect data next year from a mid-stage study by the Foster City, California-based company.
The early-stage study examined a combination of Gilead’s GS-9256 and GS-9190 with two older drugs that are the standard of care, ribavirin and Peg-interferon, according to the note.
The data will be presented at the annual meeting of the European Association for the Study of the Liver starting March 30 in Berlin.
To contact the reporter on this story: Kristen Hallam in London at khallam@bloomberg.net
To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net
Source
New Data on Multiple Bristol-Myers Squibb Investigational Hepatitis C Compounds to be Presented at The International Liver Congress 2011
March 07, 2011 01:51 PM Eastern Time
Data Demonstrate Focused Execution of the Company’s Hepatitis C R&D Strategy
PRINCETON, N.J.--(BUSINESS WIRE)--New Phase II data on multiple Bristol-Myers Squibb Company (NYSE: BMY) investigational hepatitis C compounds will be presented at The International Liver Congress (ILC), the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany, from March 30 to April 2. The data presentations, including three late-breaker presentations, demonstrate the rigorous execution of the company’s strategy to develop potential improvements in the care of patients living with Hepatitis C infection by using multiple approaches to target the virus.
Bristol-Myers Squibb will present three late-breaker presentations, including a poster presentation of the first public disclosure of 12-week data on sustained virologic response (SVR) with the NS5A inhibitor BMS-790052 in combination with PEG-Interferon alpha-2a and ribavirin (IFNα/RBV) in treatment-naïve HCV patients. Additionally, SVR 12-week data on quadruple therapy with BMS-790052, the NS3 inhibitor BMS-650032 and IFNα/RBV in null responders will be presented in the late-breaker oral presentation session on Saturday, April 2. Complete early virology response (cEVR) data from the Phase IIb EMERGE study of PEG-Interferon lambda and ribavirin versus IFNα/RBV in treatment-naïve patients will also be presented in a late-breaker oral presentation.
“Bristol-Myers Squibb is focused on advancing the science to address significant unmet medical needs for patients with liver disease,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “The data at the International Liver Congress reflect the breadth of our hepatitis C pipeline and the multiple approaches we are taking to bring forward potential new options for a disease that today impacts approximately 170 million people worldwide.”
BMS-790052 and BMS-650032 were discovered by Bristol-Myers Squibb Research and Development. PEG-Interferon lambda was discovered by ZymoGenetics, Inc., a wholly-owned subsidiary of Bristol-Myers Squibb.
The Bristol-Myers Squibb data presentations at ILC are as follows:
March 31
First report of SVR12 for a NS5A Replication complex inhibitor, BMS-790052 in combination with PEG-IFNα-2A and RBV: Phase 2a trial in treatment-naïve HCV-Genotype 1 subjects (Poster Board # 1373)
S. Pol
HĂŽpital Cochin
Paris, France
--------------------
April 1
In Vitro DAA combination studies to address HCV clinical findings (Poster Board # 803)
J.A. Lemm
Bristol-Myers Squibb
--------------------
April 1
BMS-766, A Novel HCV NS5a inhibitor with enhanced resistance coverage (Poster Board # 787)
M. Gao
Bristol-Myers Squibb
--------------------
April 1,
4:45 –5:00 p.m.
Characterization of Virologic Escape in HCV Genotype 1 Null responders receiving a combination of the NS3 protease inhibitor BMS-650032 and NS5A inhibitor BMS-790052 (Oral Session)
F. McPhee
Bristol-Myers Squibb
--------------------
April 2
BMS-650032, an NS3 inhibitor, in combination with Peginterferon Alfa-2a and Ribavirin in treatment-naĂŻve subjects with genotype-1 chronic hepatitis C infection (Poster Board # 1195)
J. Bronowicki
HĂŽpital Adultes De Brabois
Vandoeuvre Les Nancy, France
--------------------
April 2
No early virologic breakthrough observed with the HCV NS3 protease inhibitor BMS-650032 in multiple dose monotherapy studies and Phase 2a combination studies with PEG-INF alpha/RBV (Poster Board # 1223)
F. McPhee
Bristol-Myers Squibb
--------------------
April 2
The burden of hepatitis C in Europe: a propensity analysis of patient outcomes (Poster Board # 1192)
M. daCosta
DiBonaventura
Kantar Health
New York, New York
--------------------
April 2
Estimating the incidence and prevalence of hepatitis C infection in England using back projection methods (Poster Board # 1166)
P. McEwan
Cardiff Research Consortium
Cardiff, UK
Swansea University
Swansea, UK
--------------------
April 2
Cost benefit analysis of response guided therapy: dynamic disease Markov modeling for patients with chronic hepatitis (HCV) by fibrosis stages (Poster Board # 1167)
P. McEwan
Cardiff Research Consortium
Cardiff, UK
Swansea University
Swansea, UK
--------------------
April 2,
3:30 – 5:30 p.m.
Pegylated Interferon-Lambda (PEGIFN-λ) shows superior viral response with improved safety and tolerability versus PEGIFNα-2A in HCV patients (G1/2/3/4): EMERGE Phase IIb through week 12 (Late-Breakers Oral Session)
S. Zeuzem
Klinikum der Johann-Wolfgang Goethe-UniversitÀt, Frankfurt/Main, Germany
--------------------
April 2,
3:30 – 5:30 p.m.
Quadruple therapy with BMS-790052, BMS-650032 and PEG-IFN/RBV for 24 weeks results in 100% SVR12 in HCV Genotype 1 null responders (Late-Breakers Oral Session)
A. Lok
University of Michigan
Ann Arbor, Michigan
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com/ or follow us on Twitter at http://twitter.com/bmsnews.
Contacts
Bristol-Myers Squibb
Media:
Cristi Barnett, 609-252-6028
cristi.barnett@bms.com
or
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com
Source
Data Demonstrate Focused Execution of the Company’s Hepatitis C R&D Strategy
PRINCETON, N.J.--(BUSINESS WIRE)--New Phase II data on multiple Bristol-Myers Squibb Company (NYSE: BMY) investigational hepatitis C compounds will be presented at The International Liver Congress (ILC), the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany, from March 30 to April 2. The data presentations, including three late-breaker presentations, demonstrate the rigorous execution of the company’s strategy to develop potential improvements in the care of patients living with Hepatitis C infection by using multiple approaches to target the virus.
Bristol-Myers Squibb will present three late-breaker presentations, including a poster presentation of the first public disclosure of 12-week data on sustained virologic response (SVR) with the NS5A inhibitor BMS-790052 in combination with PEG-Interferon alpha-2a and ribavirin (IFNα/RBV) in treatment-naïve HCV patients. Additionally, SVR 12-week data on quadruple therapy with BMS-790052, the NS3 inhibitor BMS-650032 and IFNα/RBV in null responders will be presented in the late-breaker oral presentation session on Saturday, April 2. Complete early virology response (cEVR) data from the Phase IIb EMERGE study of PEG-Interferon lambda and ribavirin versus IFNα/RBV in treatment-naïve patients will also be presented in a late-breaker oral presentation.
“Bristol-Myers Squibb is focused on advancing the science to address significant unmet medical needs for patients with liver disease,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “The data at the International Liver Congress reflect the breadth of our hepatitis C pipeline and the multiple approaches we are taking to bring forward potential new options for a disease that today impacts approximately 170 million people worldwide.”
BMS-790052 and BMS-650032 were discovered by Bristol-Myers Squibb Research and Development. PEG-Interferon lambda was discovered by ZymoGenetics, Inc., a wholly-owned subsidiary of Bristol-Myers Squibb.
The Bristol-Myers Squibb data presentations at ILC are as follows:
March 31
First report of SVR12 for a NS5A Replication complex inhibitor, BMS-790052 in combination with PEG-IFNα-2A and RBV: Phase 2a trial in treatment-naïve HCV-Genotype 1 subjects (Poster Board # 1373)
S. Pol
HĂŽpital Cochin
Paris, France
--------------------
April 1
In Vitro DAA combination studies to address HCV clinical findings (Poster Board # 803)
J.A. Lemm
Bristol-Myers Squibb
--------------------
April 1
BMS-766, A Novel HCV NS5a inhibitor with enhanced resistance coverage (Poster Board # 787)
M. Gao
Bristol-Myers Squibb
--------------------
April 1,
4:45 –5:00 p.m.
Characterization of Virologic Escape in HCV Genotype 1 Null responders receiving a combination of the NS3 protease inhibitor BMS-650032 and NS5A inhibitor BMS-790052 (Oral Session)
F. McPhee
Bristol-Myers Squibb
--------------------
April 2
BMS-650032, an NS3 inhibitor, in combination with Peginterferon Alfa-2a and Ribavirin in treatment-naĂŻve subjects with genotype-1 chronic hepatitis C infection (Poster Board # 1195)
J. Bronowicki
HĂŽpital Adultes De Brabois
Vandoeuvre Les Nancy, France
--------------------
April 2
No early virologic breakthrough observed with the HCV NS3 protease inhibitor BMS-650032 in multiple dose monotherapy studies and Phase 2a combination studies with PEG-INF alpha/RBV (Poster Board # 1223)
F. McPhee
Bristol-Myers Squibb
--------------------
April 2
The burden of hepatitis C in Europe: a propensity analysis of patient outcomes (Poster Board # 1192)
M. daCosta
DiBonaventura
Kantar Health
New York, New York
--------------------
April 2
Estimating the incidence and prevalence of hepatitis C infection in England using back projection methods (Poster Board # 1166)
P. McEwan
Cardiff Research Consortium
Cardiff, UK
Swansea University
Swansea, UK
--------------------
April 2
Cost benefit analysis of response guided therapy: dynamic disease Markov modeling for patients with chronic hepatitis (HCV) by fibrosis stages (Poster Board # 1167)
P. McEwan
Cardiff Research Consortium
Cardiff, UK
Swansea University
Swansea, UK
--------------------
April 2,
3:30 – 5:30 p.m.
Pegylated Interferon-Lambda (PEGIFN-λ) shows superior viral response with improved safety and tolerability versus PEGIFNα-2A in HCV patients (G1/2/3/4): EMERGE Phase IIb through week 12 (Late-Breakers Oral Session)
S. Zeuzem
Klinikum der Johann-Wolfgang Goethe-UniversitÀt, Frankfurt/Main, Germany
--------------------
April 2,
3:30 – 5:30 p.m.
Quadruple therapy with BMS-790052, BMS-650032 and PEG-IFN/RBV for 24 weeks results in 100% SVR12 in HCV Genotype 1 null responders (Late-Breakers Oral Session)
A. Lok
University of Michigan
Ann Arbor, Michigan
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com/ or follow us on Twitter at http://twitter.com/bmsnews.
Contacts
Bristol-Myers Squibb
Media:
Cristi Barnett, 609-252-6028
cristi.barnett@bms.com
or
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com
Source
Merck Announces New Data Analyses for VICTRELIS™ (Boceprevir) will be Presented at The International Liver CongressTM / 2011 EASL Annual Meeting
March 07, 2011 10:44 AM Eastern Time
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that several new data analyses from Phase III studies of VICTRELIS™ (boceprevir), its investigational oral hepatitis C protease inhibitor, will be presented at The International Liver CongressTM / 46th European Association for the Study of the Liver (EASL) annual meeting. The meeting will be held from March 30 – April 3 in Berlin. In total, more than 20 abstracts highlighting Merck medicines and investigational therapies for chronic hepatitis C virus (HCV) infection will be presented, including 3 oral presentations and 17 posters for VICTRELIS.
Presented for the first time will be final results from a Phase III study of VICTRELIS administered in combination with Pegasys® (peginterferon alfa-2a) and ribavirin in adult patients with chronic HCV genotype 1 infection who were non-responders or relapsers to previous pegylated interferon and ribavirin therapy.
The EASL presentations will also include new analyses of the pivotal Phase III data for VICTRELIS administered in combination with PEGINTRON® (peginterferon alfa-2b) and ribavirin from the HCV SPRINT-2 and HCV RESPOND-2 studies:
• Response-guided therapy with VICTRELIS in combination with current standard therapy among patients with chronic HCV genotype 1, including special populations such as those with advanced fibrosis / cirrhosis;
• Overall safety profile of VICTRELIS administered in combination with current standard therapy for chronic HCV; and
• Potential predictive factors for chronic HCV treatment success, including response following 4 weeks of lead-in therapy and IL28B polymorphism.
The abstracts were published today and can be accessed on the EASL website. For program information, please visit http://www2.kenes.com/liver-congress/Pages/Home.aspx.
VICTRELIS (Boceprevir) Oral Presentations
Parallel Session: HCV Therapy, Thursday, March 31, 17:00 – 19:00, Hall 1
Boceprevir in Addition to Standard of Care Enhanced SVR in Hepatitis C Virus (HCV) Genotype-1 with Advanced Fibrosis/Cirrhosis: Subgroup Analysis of SPRINT-2 and RESPOND-2 Studies; S. Bruno et al. 17:15 – 17:30 CET
Boceprevir Resistance-Associated Variants (RAVS) are Observed More Frequently in HCV (Gt1)-Infected Patients with Poor Response to Peginterferon Alfa-2b/Ribavirin; S. Zeuzem et al. 17:45 – 18:00 CET
IL28B Polymorphism Predicts Virologic Response in Patients with Hepatitis C Genotype 1 Treated with Boceprevir (BOC) Combination Therapy. F. Poordad et al. 18:30 – 18:45 CET
VICTRELIS (Boceprevir) Key Poster Presentations
High Sustained Virologic Response (SVR) Among Genotype 1 Previous Non-Responders and Relapsers to Peginterferon/Ribavirin When Re-Treated With Boceprevir Plus Peginterferon Alfa-2A/Ribavirin. S. Flamm et al. Late-Breaker Abstract 1366. Thursday, March 31.
Response-Guided Therapy with Boceprevir Plus Peginterferon Alfa-2b/Ribavirin Reduces Duration in Naive and Peginterferon Alfa-2b/Ribavirin Previous-Treatment-Failure Patients with HCV Genotype 1. M.P. Manns et al. Abstract 448. Thursday, March 31.
Overall Safety Profile of Boceprevir Plus Peginterferon Alfa-2b/Ribavirin. M.P. Manns et al. Abstract 449. Thursday, March 31.
Four-Week Therapy with Peginterferon Alfa-2b/Ribavirin Effectively Predicts Sustained Virologic Response in Treatment-NaĂŻve and Previous-Treatment-Failure Patients with HCV-1 Treated with Boceprevir Plus Peginterferon Alfa-2b/Ribavirin. J.M. Viering et al. Abstract 481. Thursday, March 31.
Utility of Historical Data Compared to Lead-In Response in Predicting Sustained Virologic Response in Non-Responders and Relapsers to Peginterferon/Ribavirin When Re-Treated With Boceprevir+Peginterferon Alfa-2b/Ribavirin (P/R). R. Esteban et al. Abstract 418. Thursday, March 31.
About the HCV RESPOND-2 and HCV SPRINT-2 Studies
The HCV RESPOND-2 study in treatment-failure patients and the HCV SPRINT-2 study in previously untreated patients each evaluated two treatment strategies with VICTRELIS administered in combination with PEGINTRON and ribavirin to assess the ability to improve sustained virologic response (SVR) 1 and potentially shorten overall treatment duration compared to treatment with PEGINTRON and ribavirin alone:
• Response-guided therapy, in which treatment-failure patients with undetectable virus at week 8 were able to stop all treatment at 36 weeks, and in which previously untreated
• patients with undetectable virus during weeks 8 through 24 were able to stop all treatment at 28 weeks; and
• 48 weeks of treatment (4-week PEGINTRON and ribavirin lead-in followed by the addition of VICTRELIS for 44 weeks).
In both studies, all patients were treated with a 4-week lead-in of PEGINTRON (1.5 mcg/kg/week) and an investigational dose of ribavirin (600-1,400 mg/day), followed by the addition of VICTRELIS (800 mg three times a day).
As previously reported, the U.S. Food and Drug Administration has granted priority review status to the New Drug Application (NDA) for VICTRELIS and the Marketing Authorization Application (MAA) for VICTRELIS has been accepted for accelerated assessment by the European Medicines Agency. Data in the NDA and MAA have been provided in support of the proposed use of boceprevir for the treatment of chronic HCV genotype 1 infection, in combination with peginterferon alpha and ribavirin, in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.
Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. In hepatitis C, company researchers developed the first approved therapy for chronic HCV in 1991 and the first combination therapy in 1998. 2011 marks the 10-year anniversary of the introduction of PEGINTRON and ribavirin in combination therapy, a current standard therapy for chronic HCV worldwide. In addition to ongoing studies with VICTRELIS, extensive research efforts are underway to develop additional innovative oral therapies for viral hepatitis care.
About PEGINTRON
PEGINTRON is indicated for use in combination with ribavirin for the treatment of chronic hepatitis C in patients 3 years of age and older with compensated liver disease.
The following points should be considered when initiating therapy with PEGINTRON in combination with ribavirin: (1) These indications are based on achieving undetectable HCV-RNA after treatment for 24 or 48 weeks and maintaining a Sustained Virologic Response (SVR) 24 weeks after the last dose. (2) Patients with the following characteristics are less likely to benefit from re-treatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection. (3) No safety and efficacy data are available for treatment of longer than one year.
PEGINTRON is also indicated for use alone for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with interferon alpha and who are at least 18 years of age.
The following points should be considered when initiating therapy with PEGINTRON alone: Combination therapy with ribavirin is preferred over PEGINTRON monotherapy unless there are contraindications to, or significant intolerance of, ribavirin. Combination therapy provides substantially better response rates than monotherapy.
Selected Safety Information on PEGINTRON
WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED EFFECTS
Alpha interferons, including PEGINTRON, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many, but not all cases, these disorders resolve after stopping PEGINTRON therapy.
Use with Ribavirin: Ribavirin may cause birth defects and death of the unborn child. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.
Contraindications
PEGINTRON is contraindicated in patients with known hypersensitivity reactions such as urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome and toxic epidermal necrolysis to interferon alpha or any other component of the product, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6 [class B and C]) in cirrhotic CHC patients before or during treatment. PEGINTRON/ribavirin combination therapy is additionally contraindicated in women who are pregnant or may become pregnant, men whose female partners are pregnant, patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia), and patients with creatinine clearance less than 50 mL per min.
Pregnancy
Ribavirin therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Patients should use at least two effective forms of contraception and have monthly pregnancy tests during therapy and for six months after completion of therapy. If this drug is used during pregnancy, or if a patient becomes pregnant, the patient should be apprised of the potential hazard to a fetus. A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment, and for six months following cessation of treatment. Physicians and patients are encouraged to report such cases by calling 1-800-593-2214.
Patients with the following conditions should be closely monitored and may require dose reduction or discontinuation of therapy:
• Hemolytic anemia with ribavirin
• Neuropsychiatric events
• History of significant or unstable cardiac disease
• Hypothyroidism, hyperthyroidism, hyperglycemia, diabetes mellitus that cannot be effectively treated by medication
• New or worsening ophthalmologic disorders
• Ischemic and hemorrhagic cerebrovascular events
• Severe decreases in neutrophil or platelet counts
• History of autoimmune disorders
• Pancreatitis and ulcerative or hemorrhagic/ischemic colitis and pancreatitis
• Pulmonary infiltrates or pulmonary function impairment
• Child-Pugh score greater than 6 (Class B and C)
• Increased creatinine levels in patients with renal insufficiency
• Serious, acute hypersensitivity reactions and cutaneous eruptions
• Dental/periodontal disorders reported with combination therapy
• Hypertriglyceridemia may result in pancreatitis (e.g., triglycerides greater than 1000 mg/dL)
• Weight loss and growth inhibition reported with combination therapy in pediatric patients.
Life-threatening or fatal neuropsychiatric events, including suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior, sometimes directed towards others, have occurred in patients with and without a previous psychiatric disorder during PEGINTRON treatment and follow-up.
Adverse Events
Serious adverse reactions have occurred in approximately 12 percent of subjects in clinical trials. The most common serious events occurring in subjects treated with PEGINTRON and ribavirin were depression and suicidal ideation, each occurring at a frequency of less than 1 percent. The most common fatal events occurring in subjects treated with PEGINTRON and ribavirin were cardiac arrest, suicidal ideation, and suicide attempt, all occurring in less than 1 percent of subjects.
The incidence of serious adverse reactions was comparable between PEGINTRON monotherapy (about 12 percent) and PEGINTRON/ribavirin combination therapy weight-based (12 percent) or flat-dose (17 percent). In many but not all cases, adverse reactions resolved after dose reduction or discontinuation of therapy. Some patients experienced ongoing or new serious adverse reactions during the 6-month follow-up period. In a study with PEGINTRON/ribavirin (weight-based) combination therapy in adult patients, anemia with weight-based dosing occurred at an increased rate (29 percent vs. 19 percent); however, the majority of these cases were mild and responded to dose reductions. The incidence of serious adverse reactions reported for the weight-based ribavirin group was 12 percent. There were 31 deaths in clinical trials which occurred during treatment or during follow-up. Of the deaths, 19 were patients on either PEGINTRON or PEGINTRON/ribavirin combination therapy and three occurred during the follow-up period but had been on PEGINTRON/ribavirin combination therapy.
Additional serious adverse reactions seen in clinical trials at a frequency of equal to or less than 1 percent included psychosis, aggressive reaction, relapse of drug addiction/overdose; nerve palsy (facial, oculomotor); cardiomyopathy, angina, pericardial effusion, retinal ischemia, retinal artery or vein thrombosis, blindness, decreased visual acuity, optic neuritis, transient ischemic attack, supraventricular arrhythmias, loss of consciousness; neutropenia, infection (sepsis, pneumonia, abscess, cellulitis); emphysema, bronchiolitis obliterans, pleural effusion, gastroenteritis, pancreatitis, gout, hyperglycemia, hyperthyroidism and hypothyroidism, autoimmune thrombocytopenia with or without purpura, rheumatoid arthritis, interstitial nephritis, lupus-like syndrome, sarcoidosis, aggravated psoriasis, urticaria, injection site necrosis, vasculitis, and phototoxicity.
Greater than 96 percent of all subjects in clinical trials experienced one or more adverse events. Most common adverse reactions (greater than 40 percent) in adult patients receiving either PEGINTRON or PEGINTRON/ribavirin are injection site inflammation/reaction, fatigue/asthenia, headache, rigors, fevers, nausea, myalgia, and anxiety/emotional lability/irritability.
The adverse reaction profile was similar between weight-based and flat-dose PEGINTRON/ribavirin therapies. Weight-based PEGINTRON/ribavirin dosing resulted in increased rates of anemia. Most common adverse reactions with PEGINTRON/ribavirin (weight-based) therapy were psychiatric, which occurred among 68-69 percent of patients and included depression, irritability, and insomnia, each reported by approximately 30-40 percent of subjects in all treatment groups. Suicidal behavior (ideation, attempts, and suicides) occurred in 2 percent of all patients during treatment or during follow-up after treatment cessation. Other common reactions included injection site reactions, fatigue/ asthenia, headache, rigors, fever, nausea, myalgia, anxiety/emotional lability/irritability. The severity of some of these systemic symptoms tends to decrease as treatment continues.
Subjects receiving PEGINTRON/ribavirin as re-treatment after failing a previous interferon combination regimen reported adverse reactions similar to previous treatment-naĂŻve patients receiving this regimen.
In general, the adverse reaction profile in the pediatric population was similar to that observed in adults. Most common adverse reactions (greater than 25 percent) in pediatric patients receiving PEGINTRON/ribavirin are pyrexia, headache, neutropenia, fatigue, anorexia, injection site erythema, abdominal pain, and vomiting.
Please see full prescribing information at http://www.spfiles.com/pipeg-intron.pdf.
About Merck
Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit http://www.merck.com/.
Forward-Looking Statement
This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company’s plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.
The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2010 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (http://www.sec.gov/).
Please see attached Prescribing Information, Medication Guide, and Instructions for Use including Boxed Warning for PEGINTRON. The Prescribing Information, Medication Guide, and Instructions for Use are also available at http://www.spfiles.com/pipeg-intron.pdf, http://www.spfiles.com/mgpeg-intron.pdf and http://www.spfiles.com/ifupeg-intron.pdf.
Endnote
1 SVR, the protocol specified primary efficacy endpoint, is defined as achievement of undetectable HCV-RNA at 24 weeks after the end of treatment in all randomized patients treated with any study medication. Per protocol, if a patient did not have a 24-week post-treatment assessment, the patient’s 12-week post-treatment assessment was utilized.
VICTRELIS™ and PEGINTRON® are trademarks of Schering Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., USA
Pegasys® is a trademark of its respective owner and is not a trademark of Merck & Co., Inc., Whitehouse Station, N.J., USA.
Source
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that several new data analyses from Phase III studies of VICTRELIS™ (boceprevir), its investigational oral hepatitis C protease inhibitor, will be presented at The International Liver CongressTM / 46th European Association for the Study of the Liver (EASL) annual meeting. The meeting will be held from March 30 – April 3 in Berlin. In total, more than 20 abstracts highlighting Merck medicines and investigational therapies for chronic hepatitis C virus (HCV) infection will be presented, including 3 oral presentations and 17 posters for VICTRELIS.
Presented for the first time will be final results from a Phase III study of VICTRELIS administered in combination with Pegasys® (peginterferon alfa-2a) and ribavirin in adult patients with chronic HCV genotype 1 infection who were non-responders or relapsers to previous pegylated interferon and ribavirin therapy.
The EASL presentations will also include new analyses of the pivotal Phase III data for VICTRELIS administered in combination with PEGINTRON® (peginterferon alfa-2b) and ribavirin from the HCV SPRINT-2 and HCV RESPOND-2 studies:
• Response-guided therapy with VICTRELIS in combination with current standard therapy among patients with chronic HCV genotype 1, including special populations such as those with advanced fibrosis / cirrhosis;
• Overall safety profile of VICTRELIS administered in combination with current standard therapy for chronic HCV; and
• Potential predictive factors for chronic HCV treatment success, including response following 4 weeks of lead-in therapy and IL28B polymorphism.
The abstracts were published today and can be accessed on the EASL website. For program information, please visit http://www2.kenes.com/liver-congress/Pages/Home.aspx.
VICTRELIS (Boceprevir) Oral Presentations
Parallel Session: HCV Therapy, Thursday, March 31, 17:00 – 19:00, Hall 1
Boceprevir in Addition to Standard of Care Enhanced SVR in Hepatitis C Virus (HCV) Genotype-1 with Advanced Fibrosis/Cirrhosis: Subgroup Analysis of SPRINT-2 and RESPOND-2 Studies; S. Bruno et al. 17:15 – 17:30 CET
Boceprevir Resistance-Associated Variants (RAVS) are Observed More Frequently in HCV (Gt1)-Infected Patients with Poor Response to Peginterferon Alfa-2b/Ribavirin; S. Zeuzem et al. 17:45 – 18:00 CET
IL28B Polymorphism Predicts Virologic Response in Patients with Hepatitis C Genotype 1 Treated with Boceprevir (BOC) Combination Therapy. F. Poordad et al. 18:30 – 18:45 CET
VICTRELIS (Boceprevir) Key Poster Presentations
High Sustained Virologic Response (SVR) Among Genotype 1 Previous Non-Responders and Relapsers to Peginterferon/Ribavirin When Re-Treated With Boceprevir Plus Peginterferon Alfa-2A/Ribavirin. S. Flamm et al. Late-Breaker Abstract 1366. Thursday, March 31.
Response-Guided Therapy with Boceprevir Plus Peginterferon Alfa-2b/Ribavirin Reduces Duration in Naive and Peginterferon Alfa-2b/Ribavirin Previous-Treatment-Failure Patients with HCV Genotype 1. M.P. Manns et al. Abstract 448. Thursday, March 31.
Overall Safety Profile of Boceprevir Plus Peginterferon Alfa-2b/Ribavirin. M.P. Manns et al. Abstract 449. Thursday, March 31.
Four-Week Therapy with Peginterferon Alfa-2b/Ribavirin Effectively Predicts Sustained Virologic Response in Treatment-NaĂŻve and Previous-Treatment-Failure Patients with HCV-1 Treated with Boceprevir Plus Peginterferon Alfa-2b/Ribavirin. J.M. Viering et al. Abstract 481. Thursday, March 31.
Utility of Historical Data Compared to Lead-In Response in Predicting Sustained Virologic Response in Non-Responders and Relapsers to Peginterferon/Ribavirin When Re-Treated With Boceprevir+Peginterferon Alfa-2b/Ribavirin (P/R). R. Esteban et al. Abstract 418. Thursday, March 31.
About the HCV RESPOND-2 and HCV SPRINT-2 Studies
The HCV RESPOND-2 study in treatment-failure patients and the HCV SPRINT-2 study in previously untreated patients each evaluated two treatment strategies with VICTRELIS administered in combination with PEGINTRON and ribavirin to assess the ability to improve sustained virologic response (SVR) 1 and potentially shorten overall treatment duration compared to treatment with PEGINTRON and ribavirin alone:
• Response-guided therapy, in which treatment-failure patients with undetectable virus at week 8 were able to stop all treatment at 36 weeks, and in which previously untreated
• patients with undetectable virus during weeks 8 through 24 were able to stop all treatment at 28 weeks; and
• 48 weeks of treatment (4-week PEGINTRON and ribavirin lead-in followed by the addition of VICTRELIS for 44 weeks).
In both studies, all patients were treated with a 4-week lead-in of PEGINTRON (1.5 mcg/kg/week) and an investigational dose of ribavirin (600-1,400 mg/day), followed by the addition of VICTRELIS (800 mg three times a day).
As previously reported, the U.S. Food and Drug Administration has granted priority review status to the New Drug Application (NDA) for VICTRELIS and the Marketing Authorization Application (MAA) for VICTRELIS has been accepted for accelerated assessment by the European Medicines Agency. Data in the NDA and MAA have been provided in support of the proposed use of boceprevir for the treatment of chronic HCV genotype 1 infection, in combination with peginterferon alpha and ribavirin, in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.
Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. In hepatitis C, company researchers developed the first approved therapy for chronic HCV in 1991 and the first combination therapy in 1998. 2011 marks the 10-year anniversary of the introduction of PEGINTRON and ribavirin in combination therapy, a current standard therapy for chronic HCV worldwide. In addition to ongoing studies with VICTRELIS, extensive research efforts are underway to develop additional innovative oral therapies for viral hepatitis care.
About PEGINTRON
PEGINTRON is indicated for use in combination with ribavirin for the treatment of chronic hepatitis C in patients 3 years of age and older with compensated liver disease.
The following points should be considered when initiating therapy with PEGINTRON in combination with ribavirin: (1) These indications are based on achieving undetectable HCV-RNA after treatment for 24 or 48 weeks and maintaining a Sustained Virologic Response (SVR) 24 weeks after the last dose. (2) Patients with the following characteristics are less likely to benefit from re-treatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection. (3) No safety and efficacy data are available for treatment of longer than one year.
PEGINTRON is also indicated for use alone for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with interferon alpha and who are at least 18 years of age.
The following points should be considered when initiating therapy with PEGINTRON alone: Combination therapy with ribavirin is preferred over PEGINTRON monotherapy unless there are contraindications to, or significant intolerance of, ribavirin. Combination therapy provides substantially better response rates than monotherapy.
Selected Safety Information on PEGINTRON
WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED EFFECTS
Alpha interferons, including PEGINTRON, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many, but not all cases, these disorders resolve after stopping PEGINTRON therapy.
Use with Ribavirin: Ribavirin may cause birth defects and death of the unborn child. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.
Contraindications
PEGINTRON is contraindicated in patients with known hypersensitivity reactions such as urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome and toxic epidermal necrolysis to interferon alpha or any other component of the product, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6 [class B and C]) in cirrhotic CHC patients before or during treatment. PEGINTRON/ribavirin combination therapy is additionally contraindicated in women who are pregnant or may become pregnant, men whose female partners are pregnant, patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia), and patients with creatinine clearance less than 50 mL per min.
Pregnancy
Ribavirin therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Patients should use at least two effective forms of contraception and have monthly pregnancy tests during therapy and for six months after completion of therapy. If this drug is used during pregnancy, or if a patient becomes pregnant, the patient should be apprised of the potential hazard to a fetus. A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment, and for six months following cessation of treatment. Physicians and patients are encouraged to report such cases by calling 1-800-593-2214.
Patients with the following conditions should be closely monitored and may require dose reduction or discontinuation of therapy:
• Hemolytic anemia with ribavirin
• Neuropsychiatric events
• History of significant or unstable cardiac disease
• Hypothyroidism, hyperthyroidism, hyperglycemia, diabetes mellitus that cannot be effectively treated by medication
• New or worsening ophthalmologic disorders
• Ischemic and hemorrhagic cerebrovascular events
• Severe decreases in neutrophil or platelet counts
• History of autoimmune disorders
• Pancreatitis and ulcerative or hemorrhagic/ischemic colitis and pancreatitis
• Pulmonary infiltrates or pulmonary function impairment
• Child-Pugh score greater than 6 (Class B and C)
• Increased creatinine levels in patients with renal insufficiency
• Serious, acute hypersensitivity reactions and cutaneous eruptions
• Dental/periodontal disorders reported with combination therapy
• Hypertriglyceridemia may result in pancreatitis (e.g., triglycerides greater than 1000 mg/dL)
• Weight loss and growth inhibition reported with combination therapy in pediatric patients.
Life-threatening or fatal neuropsychiatric events, including suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior, sometimes directed towards others, have occurred in patients with and without a previous psychiatric disorder during PEGINTRON treatment and follow-up.
Adverse Events
Serious adverse reactions have occurred in approximately 12 percent of subjects in clinical trials. The most common serious events occurring in subjects treated with PEGINTRON and ribavirin were depression and suicidal ideation, each occurring at a frequency of less than 1 percent. The most common fatal events occurring in subjects treated with PEGINTRON and ribavirin were cardiac arrest, suicidal ideation, and suicide attempt, all occurring in less than 1 percent of subjects.
The incidence of serious adverse reactions was comparable between PEGINTRON monotherapy (about 12 percent) and PEGINTRON/ribavirin combination therapy weight-based (12 percent) or flat-dose (17 percent). In many but not all cases, adverse reactions resolved after dose reduction or discontinuation of therapy. Some patients experienced ongoing or new serious adverse reactions during the 6-month follow-up period. In a study with PEGINTRON/ribavirin (weight-based) combination therapy in adult patients, anemia with weight-based dosing occurred at an increased rate (29 percent vs. 19 percent); however, the majority of these cases were mild and responded to dose reductions. The incidence of serious adverse reactions reported for the weight-based ribavirin group was 12 percent. There were 31 deaths in clinical trials which occurred during treatment or during follow-up. Of the deaths, 19 were patients on either PEGINTRON or PEGINTRON/ribavirin combination therapy and three occurred during the follow-up period but had been on PEGINTRON/ribavirin combination therapy.
Additional serious adverse reactions seen in clinical trials at a frequency of equal to or less than 1 percent included psychosis, aggressive reaction, relapse of drug addiction/overdose; nerve palsy (facial, oculomotor); cardiomyopathy, angina, pericardial effusion, retinal ischemia, retinal artery or vein thrombosis, blindness, decreased visual acuity, optic neuritis, transient ischemic attack, supraventricular arrhythmias, loss of consciousness; neutropenia, infection (sepsis, pneumonia, abscess, cellulitis); emphysema, bronchiolitis obliterans, pleural effusion, gastroenteritis, pancreatitis, gout, hyperglycemia, hyperthyroidism and hypothyroidism, autoimmune thrombocytopenia with or without purpura, rheumatoid arthritis, interstitial nephritis, lupus-like syndrome, sarcoidosis, aggravated psoriasis, urticaria, injection site necrosis, vasculitis, and phototoxicity.
Greater than 96 percent of all subjects in clinical trials experienced one or more adverse events. Most common adverse reactions (greater than 40 percent) in adult patients receiving either PEGINTRON or PEGINTRON/ribavirin are injection site inflammation/reaction, fatigue/asthenia, headache, rigors, fevers, nausea, myalgia, and anxiety/emotional lability/irritability.
The adverse reaction profile was similar between weight-based and flat-dose PEGINTRON/ribavirin therapies. Weight-based PEGINTRON/ribavirin dosing resulted in increased rates of anemia. Most common adverse reactions with PEGINTRON/ribavirin (weight-based) therapy were psychiatric, which occurred among 68-69 percent of patients and included depression, irritability, and insomnia, each reported by approximately 30-40 percent of subjects in all treatment groups. Suicidal behavior (ideation, attempts, and suicides) occurred in 2 percent of all patients during treatment or during follow-up after treatment cessation. Other common reactions included injection site reactions, fatigue/ asthenia, headache, rigors, fever, nausea, myalgia, anxiety/emotional lability/irritability. The severity of some of these systemic symptoms tends to decrease as treatment continues.
Subjects receiving PEGINTRON/ribavirin as re-treatment after failing a previous interferon combination regimen reported adverse reactions similar to previous treatment-naĂŻve patients receiving this regimen.
In general, the adverse reaction profile in the pediatric population was similar to that observed in adults. Most common adverse reactions (greater than 25 percent) in pediatric patients receiving PEGINTRON/ribavirin are pyrexia, headache, neutropenia, fatigue, anorexia, injection site erythema, abdominal pain, and vomiting.
Please see full prescribing information at http://www.spfiles.com/pipeg-intron.pdf.
About Merck
Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit http://www.merck.com/.
Forward-Looking Statement
This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company’s plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.
The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2010 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (http://www.sec.gov/).
Please see attached Prescribing Information, Medication Guide, and Instructions for Use including Boxed Warning for PEGINTRON. The Prescribing Information, Medication Guide, and Instructions for Use are also available at http://www.spfiles.com/pipeg-intron.pdf, http://www.spfiles.com/mgpeg-intron.pdf and http://www.spfiles.com/ifupeg-intron.pdf.
Endnote
1 SVR, the protocol specified primary efficacy endpoint, is defined as achievement of undetectable HCV-RNA at 24 weeks after the end of treatment in all randomized patients treated with any study medication. Per protocol, if a patient did not have a 24-week post-treatment assessment, the patient’s 12-week post-treatment assessment was utilized.
VICTRELIS™ and PEGINTRON® are trademarks of Schering Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., USA
Pegasys® is a trademark of its respective owner and is not a trademark of Merck & Co., Inc., Whitehouse Station, N.J., USA.
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Peregrine's Bavituximab HCV Abstract Accepted for Presentation at the 46th Annual Meeting of EASL
Mar 07, 2011 08:00 ET
TUSTIN, CA--(Marketwire - March 7, 2011) - Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections, today announced that data from the company's Phase Ib dose escalation safety study of bavituximab in patients coinfected with chronic hepatitis C virus (HCV) and HIV has been accepted for presentation at the 46th annual meeting of the European Association for the Study of the Liver (EASL) taking place in Berlin, Germany from March 30 to April 3, 2011.
The abstract can be accessed through the EASL website http://www2.kenes.com/liver-congress/Pages/Home.aspx. In accordance with the EASL embargo policy, the accepted abstract titled "Escalating Repeat Dose Study of Bavituximab in Patients Co-infected with Chronic Hepatitis C Virus (HCV) and Human Immunodeficiency Virus" (poster 1239) will be presented in a poster session on Saturday, April 2, 2011.
About Peregrine Pharmaceuticals
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials for the treatment of cancer and serious viral infections. The company is pursuing multiple clinical programs in cancer and hepatitis C virus infection with its lead product candidate bavituximab and novel brain cancer agent Cotara®. Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. (http://www.avidbio.com/), which provides development and biomanufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at http://www.peregrineinc.com/.
Peregrine Contact:
Amy Figueroa
Peregrine Pharmaceuticals
(800) 987-8256
info@peregrineinc.com
Source
TUSTIN, CA--(Marketwire - March 7, 2011) - Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections, today announced that data from the company's Phase Ib dose escalation safety study of bavituximab in patients coinfected with chronic hepatitis C virus (HCV) and HIV has been accepted for presentation at the 46th annual meeting of the European Association for the Study of the Liver (EASL) taking place in Berlin, Germany from March 30 to April 3, 2011.
The abstract can be accessed through the EASL website http://www2.kenes.com/liver-congress/Pages/Home.aspx. In accordance with the EASL embargo policy, the accepted abstract titled "Escalating Repeat Dose Study of Bavituximab in Patients Co-infected with Chronic Hepatitis C Virus (HCV) and Human Immunodeficiency Virus" (poster 1239) will be presented in a poster session on Saturday, April 2, 2011.
About Peregrine Pharmaceuticals
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials for the treatment of cancer and serious viral infections. The company is pursuing multiple clinical programs in cancer and hepatitis C virus infection with its lead product candidate bavituximab and novel brain cancer agent Cotara®. Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. (http://www.avidbio.com/), which provides development and biomanufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at http://www.peregrineinc.com/.
Peregrine Contact:
Amy Figueroa
Peregrine Pharmaceuticals
(800) 987-8256
info@peregrineinc.com
Source
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