Poster presentation scheduled at AASLD November 2nd
Vital Therapies, Inc.
/PRNewswire/ -- Vital Therapies, Inc., (VTI) today announced that a poster is being presented at the American Association for the Study of Liver Diseases (AASLD) meeting in Boston on Tuesday, November 2nd. It confirms that previously reported findings of improved transplant free survival (TFS) in Chinese subjects with acute-on-chronic liver failure (ACLF) treated with the ELAD® bioartificial liver support system are maintained for up to three years.
The poster is titled "3-year follow-up of acute-on-chronic liver failure (ACLF) subjects in randomized, controlled, multicenter trial of ELAD® bioartificial liver support system in 49 Chinese subjects reveals significant transplant-free survival (TFS) benefit." It is being presented by Dr. Michael Millis, Professor of Surgery, University of Chicago, and is coauthored by Drs. Zhongping Duan and Jing Zhang, Beijing You'an Hospital, and Shaojie Xin and Shaoli You, 302 Military Hospital, Beijing.
Previously, it was reported that 84-day follow-up of ACLF subjects enrolled at two liver treatment centers in China showed statistically significant improvements in TFS for ELAD treatment compared with standard of care (SOC). At least three years following enrollment, survivors were consented and underwent a cancer screen and physical exam in accord with a questionnaire.
Of 49 subjects enrolled, 84-day TFS was 21/32 (65.6%) in the ELAD group vs. 7/17 (41.1%) in controls. Three-year TFS was 14/32 (43.8%) in the ELAD group vs. 3/12 (25%) in controls. Of 84-day survivors, 2/21 (9.5%) ELAD and 2/7 (28.6%) controls died, 1/21 (4.8%) ELAD and 0/7 controls were transplanted and 4/21 (19.0%) ELAD and 2/7 (28.6%) controls were lost to follow-up. Survival analysis reveals a statistically significant improvement in TFS (p=0.045, log-rank analysis) for the ELAD treated subjects compared with SOC. Median survival of controls was 37 days, whereas median survival of ELAD treated subjects was at least 3 years. There was no evidence of tumor development in either group.
Dr. Millis commented, "This is the first time that a long term survival benefit has been demonstrated in subjects who recovered following treatment with ELAD. It is highly encouraging to note that those subjects that survive in the short term are able to go on to extended survival without any apparent increase in mortality or morbidity compared with subjects administered standard of care."
Dr. Duan, who served as a principal investigator for the study, commented, "China has about 95 million HBV carriers and chronic hepatitis B patients, and 38 million hepatitis C patients. It is estimated that 0.1%-0.5% of these patients will experience severe hepatitis due to acute hepatocellular necrosis or hypofunction, which results in hepatic insufficiency and hepatic failure. Mortality from this condition still remains around 50%-70% even with comprehensive internal medicine treatment, leading to as many as 400,000 deaths per year in China from acute liver failure. When approved for commercial sale in China, ELAD will be the first bioartificial liver support system proven to improve survival in this population."
In order to confirm these findings from China, VTI is conducting the SILVER (Stabilization In LiVER Failure) trial in the United States, Europe and Saudi Arabia which has achieved 50% of its targeted enrollment. Should this study yield positive findings, these results, along with data from other studies, will form the basis of regulatory filings for future marketing authorization.
About ELAD and the SILVER Trial
The SILVER protocol enrolls subjects with chronic liver disease who have been hospitalized as a result of an event, such as an infection or an episode of bleeding, which has caused deterioration of their liver function (acute-on-chronic liver failure, ACLF). The trial is designed to explore whether the use of ELAD in this setting can prevent continued deterioration of liver function, called progression, and thus improve survival. The trial design uses a well-established measure of liver function called the MELD score to define the status of liver function. Treatment with ELAD, along with standard of care, is compared with standard of care alone. The time to either death or deterioration of liver function by a pre-specified amount is measured. It is postulated that the use of ELAD may extend the time to progression and improve survival in this rapidly progressing patient population.
ELAD is a biologic liver support system using a proprietary line of allogeneic human liver cells refined by several leading cell experts. The cells are stable, immortal, can be grown in unlimited quantities and retain their hepatocyte (liver cell) characteristics. About one pound of cells is used for each treatment. The cells are grown in specially designed cartridges at VTI's cell culture facility and used to treat the patient for up to ten days.
About Vital Therapies, Inc.
Vital Therapies, Inc. (VTI) is based in San Diego, California, with a wholly owned subsidiary in Beijing, China. VTI is developing the first human liver cell-based Extracorporeal Liver Assist System (ELAD). ELAD could provide support for patients with severe liver failure by processing toxins and also synthesizing proteins and metabolites that are key products of normal human liver function. ELAD is in investigational clinical trials and VTI completed a pivotal trial and filed for market approval in China in September 2007. For additional information visit http://www.vitaltherapies.com/ or contact Terry Winters, PhD, CEO, Vital Therapies at +1 858 673 6840.
ELAD is a trademark of Vital Therapies, Inc.
SOURCE Vital Therapies, Inc.
Source
October 30, 2010
Investigational Drug for Hepatitis C Boceprevir Achieved Significantly Higher Sustained Virologic Response Rates Compared to Control
Saturday, October 30, 2010 8:00 AM
Oct. 30, 2010 (Canada NewsWire Group) --
MONTREAL, Oct. 30 /CNW/ - Merck reported today that final results from two pivotal Phase III studies of boceprevir, its investigational oral hepatitis C protease inhibitor, demonstrated significantly higher sustained virologic response (SVR)1 rates in adult patients who previously failed treatment (treatment-failure; HCV RESPOND-2) and in adult patients who were new to treatment (treatment-naïve; HCV SPRINT-2) for chronic hepatitis C virus (HCV) genotype 1 compared to control, the primary objective of the studies. The results for the primary endpoints of these studies, which were first reported in a news release in August 20102, and a broad range of further data analyses from these studies are being presented in oral and poster presentations at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).3,4,5
"The most difficult aspect of managing hepatitis C is that treatment is an extremely long process that is often debilitating for many patients," said Dr. Stephen Shafran, MD, FRCPC, FACP, University of Alberta and an investigator in the SPRINT-2 trial. "These results are extremely exciting because boceprevir substantially increased success rates compared to standard therapy and many of the patients were able to be treated for 28 to 36 weeks."
An estimated 242,500 individuals are infected with HCV in Canada6 and in 2007, there were nearly 8,000 newly infected individuals.7 It is the leading cause of liver transplants in Canada.8
The HCV RESPOND-2 and HCV SPRINT-2 studies each evaluated two treatment strategies with boceprevir administered in combination with ribavirin plus peginterferon alfa-2b (Peg/riba) to assess whether the addition of boceprevir could improve SVR rates and potentially shorten overall treatment duration compared to the use of Peg/riba alone for 48 weeks, which is the current standard duration of therapy. In each study, patients were randomized to three groups:
Response-guided therapy (RGT), in which total treatment duration was based on certain early response criteria. Treatment-failure patients with undetectable virus (HCV-RNA) at week 8 were eligible to stop all treatment at 36 weeks. Treatment-naïve patients with undetectable virus (HCV-RNA) during weeks 8 through 24 were eligible to stop all treatment at 28 weeks.
48 weeks of treatment, in which patients received a 4-week Peg/riba lead-in followed by the addition of boceprevir for 44 weeks.
Control, in which patients received Peg/riba for 48 weeks.
In both studies, all patients were treated with a 4-week lead-in of peginterferon alfa-2b 1.5 mcg/kg/week and an investigational dose of 600-1,400 mg/day of ribavirin, followed by the addition of boceprevir (800 mg three times a day).
In primary results, addition of boceprevir significantly increased SVR rates compared to control
HCV RESPOND-2, which was conducted at U.S., Canadian and other international sites, included 403 adult patients who had failed prior therapy, including patients who relapsed or were non-responders to prior treatment with peginterferon and ribavirin. HCV SPRINT-2 was conducted in 1,097 treatment-naïve adult patients at U.S., Canadian and other international sites who were enrolled in two separate cohorts, one with 938 non-Black patients and the other with 159 Black patients.
As previously reported, the primary results of these two studies were as follows: In treatment-failure patients in HCV RESPOND-2, boceprevir increased SVR rates to 59 percent for the RGT arm (95/162) and 66 percent for the 48-week treatment arm (107/161) compared to 21 percent for control (17/80). In treatment-naïve patients in HCV SPRINT-2, boceprevir increased SVR rates to 63 percent for the RGT arm (233/368) and 66 percent for the 48-week treatment arm (242/366), compared to 38 percent for control (137/363). (All primary endpoints achieved statistical significance of p<0.0001 based on intent-to-treat analyses.)
Researchers present new analyses on boceprevir response-guided therapy
In secondary analyses presented for the first time at AASLD, researchers reported that nearly half of all patients in the boceprevir RGT arms met early response criteria and received a shorter total duration of therapy:
In the RGT arm of the treatment-failure study, 46 percent (74/162) of patients met the early response criteria and were eligible to stop all treatment at 36 weeks, which is 12 weeks shorter than current standard therapy. In these patients, the SVR rate was 86 percent (64/74).
In the RGT arm of the treatment-naïve study, 44 percent of patients (162/368) met the early response criteria and were eligible to stop all treatment at 28 weeks, which is 20 weeks shorter than current standard therapy. In these patients, the SVR rates were 97 percent (143/147) in non-Black treatment-naïve patients and 87 percent (13/15) in Black treatment-naïve patients.
For the corresponding patients in the boceprevir 48-week treatment arms of these studies, the SVR rates were 88 percent (74/84) in treatment-failure patients, 96 percent (137/142) in non-Black treatment-naïve patients and 95 percent (18/19) in Black treatment-naïve patients.
Patients in the boceprevir RGT arms of these studies who did not meet the early response criteria and were treated for up to 48 weeks also achieved substantially higher SVR rates compared to control. In these patients, the SVR rates were 40 percent (29/72) in treatment-failure patients, 74 percent (52/70) in non-Black treatment-naïve patients and 58 percent (7/12) in Black treatment-naïve patients.
"One of the hardest parts of treating patients with hepatitis C is seeing how physically and emotionally demanding the process is for them to go through," said Jo-Ann Ford, RN, MSN, Associate Director of Clinical Research, BC Hepatitis Program. "Boceprevir provides options to Health Care Professionals to adapt treatment based on individual patient response, avoiding unnecessary exposure to additional weeks of therapy."
Tolerability profile in treatment-failure patients
The five most common treatment-related adverse events in the HCV RESPOND-2 study reported for the boceprevir RGT arm, boceprevir 48-week treatment arm and control, respectively, were: fatigue (54, 57, and 50 percent), headache (41, 39 and 48 percent), nausea (44, 39 and 38 percent), chills (35, 30 and 30 percent) and influenza-like illness (23, 23 and 25 percent). Anemia was reported in 43, 46 and 20 percent of patients in the study arms, respectively. Serious adverse events were reported in 10, 14 and 5 percent of patients in the study arms, respectively.
Treatment discontinuations due to adverse events over the total course of all treatment were 8 percent and 12 percent for the boceprevir RGT and 48-week treatment arms, respectively, compared to 3 percent for control. Treatment discontinuations due to anemia were 0 percent and 3 percent for the boceprevir arms, respectively, compared to 0 percent for control. Erythropoietin (EPO) for management of anemia was allowed at the discretion of the investigator per the study protocol, and was used by 41 and 46 percent of patients in the boceprevir RGT and 48-week treatment arms, respectively, compared to 21 percent for control.
Tolerability profile in treatment-naïve patients
The five most common treatment-related adverse events in the HCV SPRINT-2 study reported for the boceprevir RGT arm, boceprevir 48-week treatment arm and control, respectively, were: fatigue (52, 57 and 59 percent), headache (45, 43 and 42 percent), nausea (46, 42 and 40 percent), anemia (49, 49 and 29 percent) and dysgeusia (bad taste) (37, 43 and 18 percent). Serious adverse events were reported in 11, 12 and 9 percent of patients in the study arms, respectively.
Treatment discontinuations due to adverse events over the total course of all treatment were 12 percent and 16 percent for the boceprevir RGT and 48-week treatment arms, respectively, compared to 16 percent for control. Treatment discontinuations due to anemia were 2 percent for each of the boceprevir treatment arms compared to 1 percent for control. EPO for management of anemia was allowed at the discretion of the investigator per the study protocol, and was used by 43 percent of patients in each of the boceprevir treatment arms compared to 24 percent for control.
The HCV RESPOND-2 and HCV SPRINT-2 studies each employed futility or "stopping" rules, whereby patients in any treatment arm who had detectable virus at week 12 in the HCV RESPOND-2 study or at week 24 in the HCV SPRINT-2 study were considered treatment failures and discontinued all treatment. These stopping rules allowed for patients in the studies who did not respond to treatment to have their therapy stopped early, thereby avoiding unnecessary treatment.
Merck's global commitment to advancing hepatitis 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. Extensive research efforts are underway to develop differentiated oral therapies that bring innovation to viral hepatitis care.
About boceprevir
Boceprevir is not approved in Canada.
About ribavirin plus peginterferon alfa-2b:
Ribavirin plus peginterferon alfa-2b, known as PEGETRON® in Canada, is indicated for the treatment of adult patients (≥ 18 years of age) with chronic hepatitis C who have compensated liver disease and are positive for HCV-RNA, including patients who have not received previous treatment or who failed prior treatment with interferon alpha (pegylated or non-pegylated) and ribavirin combination therapy.1
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 2009 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/).
1 ® Registered trademark of Schering-Plough Ltd. Used under license.
1 SVR, the protocol specified primary efficacy endpoint of the studies, 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.
2 Merck news release: In Pivotal Phase III Studies, Merck's Investigational Medicine Boceprevir Helped Majority of Patients with Chronic Hepatitis C Genotype 1 Infection Achieve Sustained Virologic Response, the Primary Endpoint of the Studies. Available at: http://www.merck.com/newsroom/news-release-archive/home.html. Aug. 4, 2010.
3 B.R. Bacon et al. HCV RESPOND-2 Final Results: High Sustained Virologic Response Among Genotype 1 Previous Non-Responders and Relapsers to Peginterferon/Ribavirin when Re-Treated with Boceprevir Plus PEGINTRON (Peginterferon alfa-2b)/Ribavirin. Abstract 216.
4 F. Poordad et al. Boceprevir (BOC) Combined with Peginterferon alfa-2b/Ribavirin (P/R) for Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype (G) 1: SPRINT-2 Final Results. Abstract LB-4.
5 J. Bronowicki et al. Response-Guided Therapy (RGT) with Boceprevir (BOC) + Peginterferon alfa-2b/Ribavirin (P/R) for Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype (G) 1 Was Similar to a 48-Wk Fixed-Duration Regimen with BOC + P/R in SPRINT-2. Abstract LB-15.
6 Health Canada. http://www.phac-aspc.gc.ca/hepc/faq-eng.php . Accessed Oct. 28. 2010.
7 Health Canada. http://www.phac-aspc.gc.ca/hepc/faq-eng.php . Accessed Oct. 28. 2010.
8 Canadian Liver Foundation. http://www.liver.ca/Liver_Disease/ . Accessed Oct. 28. 2010.
Media Contacts:
Mona Aubin Merck
514 428-3768
mona.aubin@merck.com
Julia Alter Edelman
416-849-2996
julia.alter@edelman.com
(Source: CNW )
(Source: Quotemedia)
Source
Oct. 30, 2010 (Canada NewsWire Group) --
MONTREAL, Oct. 30 /CNW/ - Merck reported today that final results from two pivotal Phase III studies of boceprevir, its investigational oral hepatitis C protease inhibitor, demonstrated significantly higher sustained virologic response (SVR)1 rates in adult patients who previously failed treatment (treatment-failure; HCV RESPOND-2) and in adult patients who were new to treatment (treatment-naïve; HCV SPRINT-2) for chronic hepatitis C virus (HCV) genotype 1 compared to control, the primary objective of the studies. The results for the primary endpoints of these studies, which were first reported in a news release in August 20102, and a broad range of further data analyses from these studies are being presented in oral and poster presentations at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).3,4,5
"The most difficult aspect of managing hepatitis C is that treatment is an extremely long process that is often debilitating for many patients," said Dr. Stephen Shafran, MD, FRCPC, FACP, University of Alberta and an investigator in the SPRINT-2 trial. "These results are extremely exciting because boceprevir substantially increased success rates compared to standard therapy and many of the patients were able to be treated for 28 to 36 weeks."
An estimated 242,500 individuals are infected with HCV in Canada6 and in 2007, there were nearly 8,000 newly infected individuals.7 It is the leading cause of liver transplants in Canada.8
The HCV RESPOND-2 and HCV SPRINT-2 studies each evaluated two treatment strategies with boceprevir administered in combination with ribavirin plus peginterferon alfa-2b (Peg/riba) to assess whether the addition of boceprevir could improve SVR rates and potentially shorten overall treatment duration compared to the use of Peg/riba alone for 48 weeks, which is the current standard duration of therapy. In each study, patients were randomized to three groups:
Response-guided therapy (RGT), in which total treatment duration was based on certain early response criteria. Treatment-failure patients with undetectable virus (HCV-RNA) at week 8 were eligible to stop all treatment at 36 weeks. Treatment-naïve patients with undetectable virus (HCV-RNA) during weeks 8 through 24 were eligible to stop all treatment at 28 weeks.
48 weeks of treatment, in which patients received a 4-week Peg/riba lead-in followed by the addition of boceprevir for 44 weeks.
Control, in which patients received Peg/riba for 48 weeks.
In both studies, all patients were treated with a 4-week lead-in of peginterferon alfa-2b 1.5 mcg/kg/week and an investigational dose of 600-1,400 mg/day of ribavirin, followed by the addition of boceprevir (800 mg three times a day).
In primary results, addition of boceprevir significantly increased SVR rates compared to control
HCV RESPOND-2, which was conducted at U.S., Canadian and other international sites, included 403 adult patients who had failed prior therapy, including patients who relapsed or were non-responders to prior treatment with peginterferon and ribavirin. HCV SPRINT-2 was conducted in 1,097 treatment-naïve adult patients at U.S., Canadian and other international sites who were enrolled in two separate cohorts, one with 938 non-Black patients and the other with 159 Black patients.
As previously reported, the primary results of these two studies were as follows: In treatment-failure patients in HCV RESPOND-2, boceprevir increased SVR rates to 59 percent for the RGT arm (95/162) and 66 percent for the 48-week treatment arm (107/161) compared to 21 percent for control (17/80). In treatment-naïve patients in HCV SPRINT-2, boceprevir increased SVR rates to 63 percent for the RGT arm (233/368) and 66 percent for the 48-week treatment arm (242/366), compared to 38 percent for control (137/363). (All primary endpoints achieved statistical significance of p<0.0001 based on intent-to-treat analyses.)
Researchers present new analyses on boceprevir response-guided therapy
In secondary analyses presented for the first time at AASLD, researchers reported that nearly half of all patients in the boceprevir RGT arms met early response criteria and received a shorter total duration of therapy:
In the RGT arm of the treatment-failure study, 46 percent (74/162) of patients met the early response criteria and were eligible to stop all treatment at 36 weeks, which is 12 weeks shorter than current standard therapy. In these patients, the SVR rate was 86 percent (64/74).
In the RGT arm of the treatment-naïve study, 44 percent of patients (162/368) met the early response criteria and were eligible to stop all treatment at 28 weeks, which is 20 weeks shorter than current standard therapy. In these patients, the SVR rates were 97 percent (143/147) in non-Black treatment-naïve patients and 87 percent (13/15) in Black treatment-naïve patients.
For the corresponding patients in the boceprevir 48-week treatment arms of these studies, the SVR rates were 88 percent (74/84) in treatment-failure patients, 96 percent (137/142) in non-Black treatment-naïve patients and 95 percent (18/19) in Black treatment-naïve patients.
Patients in the boceprevir RGT arms of these studies who did not meet the early response criteria and were treated for up to 48 weeks also achieved substantially higher SVR rates compared to control. In these patients, the SVR rates were 40 percent (29/72) in treatment-failure patients, 74 percent (52/70) in non-Black treatment-naïve patients and 58 percent (7/12) in Black treatment-naïve patients.
"One of the hardest parts of treating patients with hepatitis C is seeing how physically and emotionally demanding the process is for them to go through," said Jo-Ann Ford, RN, MSN, Associate Director of Clinical Research, BC Hepatitis Program. "Boceprevir provides options to Health Care Professionals to adapt treatment based on individual patient response, avoiding unnecessary exposure to additional weeks of therapy."
Tolerability profile in treatment-failure patients
The five most common treatment-related adverse events in the HCV RESPOND-2 study reported for the boceprevir RGT arm, boceprevir 48-week treatment arm and control, respectively, were: fatigue (54, 57, and 50 percent), headache (41, 39 and 48 percent), nausea (44, 39 and 38 percent), chills (35, 30 and 30 percent) and influenza-like illness (23, 23 and 25 percent). Anemia was reported in 43, 46 and 20 percent of patients in the study arms, respectively. Serious adverse events were reported in 10, 14 and 5 percent of patients in the study arms, respectively.
Treatment discontinuations due to adverse events over the total course of all treatment were 8 percent and 12 percent for the boceprevir RGT and 48-week treatment arms, respectively, compared to 3 percent for control. Treatment discontinuations due to anemia were 0 percent and 3 percent for the boceprevir arms, respectively, compared to 0 percent for control. Erythropoietin (EPO) for management of anemia was allowed at the discretion of the investigator per the study protocol, and was used by 41 and 46 percent of patients in the boceprevir RGT and 48-week treatment arms, respectively, compared to 21 percent for control.
Tolerability profile in treatment-naïve patients
The five most common treatment-related adverse events in the HCV SPRINT-2 study reported for the boceprevir RGT arm, boceprevir 48-week treatment arm and control, respectively, were: fatigue (52, 57 and 59 percent), headache (45, 43 and 42 percent), nausea (46, 42 and 40 percent), anemia (49, 49 and 29 percent) and dysgeusia (bad taste) (37, 43 and 18 percent). Serious adverse events were reported in 11, 12 and 9 percent of patients in the study arms, respectively.
Treatment discontinuations due to adverse events over the total course of all treatment were 12 percent and 16 percent for the boceprevir RGT and 48-week treatment arms, respectively, compared to 16 percent for control. Treatment discontinuations due to anemia were 2 percent for each of the boceprevir treatment arms compared to 1 percent for control. EPO for management of anemia was allowed at the discretion of the investigator per the study protocol, and was used by 43 percent of patients in each of the boceprevir treatment arms compared to 24 percent for control.
The HCV RESPOND-2 and HCV SPRINT-2 studies each employed futility or "stopping" rules, whereby patients in any treatment arm who had detectable virus at week 12 in the HCV RESPOND-2 study or at week 24 in the HCV SPRINT-2 study were considered treatment failures and discontinued all treatment. These stopping rules allowed for patients in the studies who did not respond to treatment to have their therapy stopped early, thereby avoiding unnecessary treatment.
Merck's global commitment to advancing hepatitis 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. Extensive research efforts are underway to develop differentiated oral therapies that bring innovation to viral hepatitis care.
About boceprevir
Boceprevir is not approved in Canada.
About ribavirin plus peginterferon alfa-2b:
Ribavirin plus peginterferon alfa-2b, known as PEGETRON® in Canada, is indicated for the treatment of adult patients (≥ 18 years of age) with chronic hepatitis C who have compensated liver disease and are positive for HCV-RNA, including patients who have not received previous treatment or who failed prior treatment with interferon alpha (pegylated or non-pegylated) and ribavirin combination therapy.1
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 2009 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/).
1 ® Registered trademark of Schering-Plough Ltd. Used under license.
1 SVR, the protocol specified primary efficacy endpoint of the studies, 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.
2 Merck news release: In Pivotal Phase III Studies, Merck's Investigational Medicine Boceprevir Helped Majority of Patients with Chronic Hepatitis C Genotype 1 Infection Achieve Sustained Virologic Response, the Primary Endpoint of the Studies. Available at: http://www.merck.com/newsroom/news-release-archive/home.html. Aug. 4, 2010.
3 B.R. Bacon et al. HCV RESPOND-2 Final Results: High Sustained Virologic Response Among Genotype 1 Previous Non-Responders and Relapsers to Peginterferon/Ribavirin when Re-Treated with Boceprevir Plus PEGINTRON (Peginterferon alfa-2b)/Ribavirin. Abstract 216.
4 F. Poordad et al. Boceprevir (BOC) Combined with Peginterferon alfa-2b/Ribavirin (P/R) for Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype (G) 1: SPRINT-2 Final Results. Abstract LB-4.
5 J. Bronowicki et al. Response-Guided Therapy (RGT) with Boceprevir (BOC) + Peginterferon alfa-2b/Ribavirin (P/R) for Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype (G) 1 Was Similar to a 48-Wk Fixed-Duration Regimen with BOC + P/R in SPRINT-2. Abstract LB-15.
6 Health Canada. http://www.phac-aspc.gc.ca/hepc/faq-eng.php . Accessed Oct. 28. 2010.
7 Health Canada. http://www.phac-aspc.gc.ca/hepc/faq-eng.php . Accessed Oct. 28. 2010.
8 Canadian Liver Foundation. http://www.liver.ca/Liver_Disease/ . Accessed Oct. 28. 2010.
Media Contacts:
Mona Aubin Merck
514 428-3768
mona.aubin@merck.com
Julia Alter Edelman
416-849-2996
julia.alter@edelman.com
(Source: CNW )
(Source: Quotemedia)
Source
Creating Functional Hepatic Tissue in a Bioengineered Human Liver
Presented: Sunday, 31 October 2010, 11:45 am Eastern Time
By American Association for the Study of Liver Diseases (AASLD)
Published: Saturday, Oct. 30, 2010 - 6:00 am
BOSTON, Oct. 30 -- /PRNewswire/ -- Researchers at Wake Forest University Baptist Medical Center's Institute for Regenerative Medicine demonstrated the generation of a bioengineered human liver organoid using a liver bioscaffold made from an intact liver extracellular matrix, and filled (seeded) with primary human liver progenitor and endothelial cells.
The ability to generate a liver scaffold and preserve its vascular network had been demonstrated previously. These studies showed the possibility of seeding these bioscaffolds with liver cells from animals, but the possibility of generating functional human hepatic tissue was still in question.
The current study demonstrated that human liver cells can be seeded through the portal vein of the liver bioscaffold, and can be maintained in a specialized bioreactor with constant culture medium perfusion up to one week. Progressive human liver tissue formation was documented, as well as liver-associated functions. Widespread cell proliferation inside the bioengineered liver tissue with low cell apoptosis was also observed.
According to Pedro Baptista, PharmD, PhD, "These studies provide the basis to begin transplantation of bioengineered livers in small animal models. We believe that this functional hepatic tissue, once transplanted, will maintain and further gain function as it progressively grows and develops in vivo. Also, the exclusive use of human cells opens new horizons for drug testing and toxicology studies. This will more closely mimic drug metabolism in the human liver, which animal models can, at times, be extremely difficult to predict."
"This technology may provide a new approach for liver bioengineering, enabling the use of organ scaffolds with human cells to produce functional human liver tissue," said Dr. Baptista.
The researcher hails this as a new approach to whole organ liver bioengineering that might prove to be critical for drug discovery and treatment of liver disease. "This laboratory-generated hepatic tissue offers great potential as a drug discovery and toxicology testing platform. Moreover, we believe that further translation into larger animal species opens the door for the generation of transplantable bioengineered human livers that can help patients with end-stage chronic liver disease who are waiting for a donor."
Abstract title:
The Use of Whole Organ Decellularization for the Bioengineering of a Human Vascularized Liver
About the AASLD
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Boston, Massachusetts, October 29-November 2, will bring together more than 7,500 researchers from 55 countries.
A pressroom will be available from October 30 at the annual meeting. For copies of abstracts and press releases, or to arrange for pre-conference research interviews contact Gregory Bologna at 703-299-9766. To pre-register, call Ann Haran at 703-299-9766.
Press releases and all abstracts are available online at http://www.aasld.org/.
Media Contact: Gregory Bologna
703/299-9766
gbologna@aasld.org
Press Room: October 30 – November 2, 2010
Hynes Convention Center, Room 208
Telephone: 617-954-3106
Researchers: Pedro Baptista, PharmD, PhD; Shay Soker, PhD
Email: pbaptist@wfubmc.edu; ssoker@wfubmc.edu
Phone: 336-713-1325
This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.xpresspress.com/.
SOURCE American Association for the Study of Liver Diseases (AASLD)
Source
Also See: Wake Forest scientists successfully grow 'miniature livers'
By American Association for the Study of Liver Diseases (AASLD)
Published: Saturday, Oct. 30, 2010 - 6:00 am
BOSTON, Oct. 30 -- /PRNewswire/ -- Researchers at Wake Forest University Baptist Medical Center's Institute for Regenerative Medicine demonstrated the generation of a bioengineered human liver organoid using a liver bioscaffold made from an intact liver extracellular matrix, and filled (seeded) with primary human liver progenitor and endothelial cells.
The ability to generate a liver scaffold and preserve its vascular network had been demonstrated previously. These studies showed the possibility of seeding these bioscaffolds with liver cells from animals, but the possibility of generating functional human hepatic tissue was still in question.
The current study demonstrated that human liver cells can be seeded through the portal vein of the liver bioscaffold, and can be maintained in a specialized bioreactor with constant culture medium perfusion up to one week. Progressive human liver tissue formation was documented, as well as liver-associated functions. Widespread cell proliferation inside the bioengineered liver tissue with low cell apoptosis was also observed.
According to Pedro Baptista, PharmD, PhD, "These studies provide the basis to begin transplantation of bioengineered livers in small animal models. We believe that this functional hepatic tissue, once transplanted, will maintain and further gain function as it progressively grows and develops in vivo. Also, the exclusive use of human cells opens new horizons for drug testing and toxicology studies. This will more closely mimic drug metabolism in the human liver, which animal models can, at times, be extremely difficult to predict."
"This technology may provide a new approach for liver bioengineering, enabling the use of organ scaffolds with human cells to produce functional human liver tissue," said Dr. Baptista.
The researcher hails this as a new approach to whole organ liver bioengineering that might prove to be critical for drug discovery and treatment of liver disease. "This laboratory-generated hepatic tissue offers great potential as a drug discovery and toxicology testing platform. Moreover, we believe that further translation into larger animal species opens the door for the generation of transplantable bioengineered human livers that can help patients with end-stage chronic liver disease who are waiting for a donor."
Abstract title:
The Use of Whole Organ Decellularization for the Bioengineering of a Human Vascularized Liver
About the AASLD
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Boston, Massachusetts, October 29-November 2, will bring together more than 7,500 researchers from 55 countries.
A pressroom will be available from October 30 at the annual meeting. For copies of abstracts and press releases, or to arrange for pre-conference research interviews contact Gregory Bologna at 703-299-9766. To pre-register, call Ann Haran at 703-299-9766.
Press releases and all abstracts are available online at http://www.aasld.org/.
Media Contact: Gregory Bologna
703/299-9766
gbologna@aasld.org
Press Room: October 30 – November 2, 2010
Hynes Convention Center, Room 208
Telephone: 617-954-3106
Researchers: Pedro Baptista, PharmD, PhD; Shay Soker, PhD
Email: pbaptist@wfubmc.edu; ssoker@wfubmc.edu
Phone: 336-713-1325
This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.xpresspress.com/.
SOURCE American Association for the Study of Liver Diseases (AASLD)
Source
Also See: Wake Forest scientists successfully grow 'miniature livers'
New Data From Phase 3 Studies Showed Superior SVR (Viral Cure) Rates Achieved with Telaprevir-Based Combination Therapy in People with Hepatitis C, Regardless of Race or Stage of Liver Disease
Industry updates: Oct 30, 2010
Source:biowire
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced new data from its Phase 3 studies of people with genotype 1 chronic hepatitis C who have not been treated previously. In these studies, the majority of people achieved superior sustained viral response (SVR or viral cure) rates with a telaprevir-based combination regimen, compared to current therapies, regardless of race/ethnicity or stage of liver fibrosis (factors known to limit response to current hepatitis C treatments). Patients in the ADVANCE and ILLUMINATE studies were given telaprevir with pegylated-interferon and ribavirin for the first 12 weeks of the studies, followed by treatment with pegylated-interferon and ribavirin alone for a total of either 24 weeks or 48 weeks based on their response to treatment at weeks 4 and 12. Final data from the Phase 3 ADVANCE and ILLUMINATE studies are being presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), which takes place in Boston October 29 to November 2.
“In our Phase 3 program, starting people with 12 weeks of telaprevir-based combination therapy resulted in significant improvements in viral cure rates, regardless of race, extent of liver damage or experience with prior treatment,” said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. “The results of the ADVANCE and ILLUMINATE studies represent a major milestone in the development of telaprevir and offer hope for doctors and the millions of people living with hepatitis C who need new and more effective medicines.”
Vertex Pharmaceuticals Incorporated is developing telaprevir in collaboration with Tibotec and Mitsubishi Tanabe Pharma.
Results from ADVANCE & ILLUMINATE
Overall in ADVANCE, 75% of people treated with a telaprevir-based combination regimen for 12 weeks, followed by an additional 12 or 36 weeks of pegylated-interferon and ribavirin alone, achieved SVR, compared to 44% of people treated with 48 weeks of pegylated-interferon and ribavirin alone. New data from this study showed that 62% of African Americans/Blacks achieved SVR with telaprevir compared to 25% of African Americans/Blacks who were treated with pegylated-interferon and ribavirin alone. Additionally, 62% of people with advanced liver fibrosis or cirrhosis (scarring of the liver) achieved SVR with telaprevir compared to 33% who were treated with pegylated-interferon and ribavirin alone.
Response-guided therapy was used in ADVANCE, whereby patients whose virus was undetectable at weeks 4 and 12 of treatment with telaprevir-based therapy were eligible to reduce their treatment time by half – from 48 weeks to 24 weeks. ILLUMINATE was designed to confirm both the use of response-guided therapy and to evaluate whether there was any benefit in extending therapy from 24 weeks to 48 weeks in people who met these criteria. In ADVANCE and ILLUMINATE, 58% and 65% of people, respectively, met these criteria for 24-week total treatment. In ILLUMINATE there was no benefit in extending therapy to 48 weeks.
In ILLUMINATE, 72% of people overall achieved SVR with telaprevir-based therapy. New data from this study showed that 60% of African Americans/Blacks and 63% of people with advanced liver fibrosis or cirrhosis achieved SVR with telaprevir-based therapy in the overall study analysis. Of African Americans/Blacks whose virus was undetectable at weeks 4 and 12, 88% of people achieved SVR in both the 24-week and 48-week randomized treatment arms. There was no control arm of pegylated-interferon and ribavirin alone in ILLUMINATE.
The safety and tolerability profile of telaprevir was consistent in both trials, with low discontinuation rates of all drugs during the telaprevir treatment phase due to adverse events.
“Less than half of people with the most common form of hepatitis C - genotype 1- achieve a viral cure with currently approved medicines, and factors such as race and extent of liver fibrosis can further limit cure rates to less than a third,” said Ira Jacobson, M.D., Chief of the Division of Gastroenterology and Hepatology, at New York-Presbyterian Hospital/Weill Cornell Medical Center, and the Vincent Astor Distinguished Professor of Medicine at Weill Cornell Medical College. “After treatment with telaprevir-based combination therapy in the ADVANCE study, 75% of people overall achieved a viral cure. Importantly, 62% of African Americans/Blacks and people with extensive liver disease achieved a viral cure – nearly twice as many as those who received pegylated-interferon and ribavirin alone.”
“Many patients today are not motivated to begin hepatitis C therapy given the year-long treatment time and low cure rates with approved therapies,” said Kenneth Sherman, M.D., Ph.D., Professor of Medicine at the University of Cincinnati College of Medicine, Director of the Division of Digestive Diseases for UC Health. “Data from the ILLUMINATE study are extremely promising and showed that high viral cure rates and shorter treatment duration may be possible for the majority of people who have not been treated previously.”
Additional Data at AASLD
Results from the EXTEND study are also being presented at the meeting. EXTEND is a long-term follow-up study of patients who received telaprevir-based regimens in the PROVE Phase 2 clinical trials and was designed to evaluate whether people maintain their SVR (viral cure) over time and to observe changes in hepatitis C viral resistance variants in those telaprevir-treated patients who had not achieved SVR. The results showed that after an average of two years of follow-up, SVR rates with telaprevir were durable in 99% (122/123) of patients with SVR who took part in the trials. Among patients who did not achieve SVR and who had resistant variants at the start of the EXTEND study, 89% (50/56) no longer had detectable variants.
Safety & Tolerability Results from ADVANCE and ILLUMINATE
The safety and tolerability results of telaprevir-based combination regimens were consistent in the ADVANCE and ILLUMINATE studies. Treatment discontinuation rates of all drugs due to adverse events during the telaprevir treatment phase in the ADVANCE study were low in the telaprevir arms (7% to 8%) and the control arm (4%). The most common adverse events (>25% of people) reported in both studies, regardless of treatment arm, were rash, fatigue, pruritis, headache, nausea, anemia, insomnia, diarrhea, influenza-like symptoms and pyrexia. The majority of these adverse events were mild to moderate.
To optimize each patient’s opportunity to achieve viral cure in the Phase 3 studies, sequential discontinuation of the drugs was recommended if discontinuation of treatment was necessary due to adverse events. Investigators were not required to discontinue the use of all three drugs at once, and, for example, patients may have continued on pegylated-interferon and ribavirin after discontinuing telaprevir only.
In ADVANCE, discontinuation of telaprevir or placebo only due to adverse events during the telaprevir treatment phase occurred in 11% of people in the 12-week telaprevir arm, 7% of people in the 8-week telaprevir arm and 1% of people in the control arm. In ILLUMINATE, 12% of people overall discontinued telaprevir only due to adverse events during the telaprevir treatment phase.
Discontinuation of all drugs due to either rash or anemia was low in both studies (1% to 3%). Rash was primarily characterized as eczema-like, manageable and resolved upon stopping telaprevir. Ninety-two percent and 95% of rash was mild to moderate in ADVANCE and ILLUMINATE, respectively. Rash was managed with the use of topical corticosteroids and antihistamines, and anemia was primarily managed by reducing the dose of ribavirin. The use of erythropoiesis-stimulating agents (ESAs) were not allowed in any of the Phase 3 clinical studies.
Planned NDA Submission and Additional Phase 3 Analysis
Three Phase 3 studies, ADVANCE, ILLUMINATE and REALIZE will form the basis of the clinical portion of the telaprevir New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA), which is expected to be complete in the fourth quarter of 2010. REALIZE evaluated telaprevir in three groups of people with genotype 1 hepatitis C who did not achieve a viral cure with previous treatment: (1) those who relapsed, (2) those who achieved a partial response and (3) those who had a null response to prior treatment (<2 log10 reduction in HCV RNA at week 12). Topline results from REALIZE were reported in a press release on September 7, 2010.
At a 2010 medical meeting,Vertex’s collaborator Tibotec reported results on the correlation of poor interferon response (<1 log10 reduction in HCV RNA at week 4) with the standard definition for null response (< 2 log10 reduction in HCV RNA at week 12).12,13 In these results, 38% (9/24) of patients who had a less than 1 log10 response at week 4 subsequently had a greater than 2 log10 reduction in HCV RNA at week 12. This analysis suggested that some patients would be misclassified as null responders using the definition of a less than 1 log10 reduction in HCV RNA at week 4.
An additional sub-analysis in the REALIZE study showed that among the combined partial responder and relapser patients in the telaprevir delayed start (lead-in) arm of the REALIZE study, 18% (31/171) had a less than 1 log10 reduction in HCV RNA at week 4 and of these patients, 58% (18/31) achieved SVR compared to 31% (46/147) of patients prospectively-defined as prior null responders (<2 log10 at week 12) in the combined telaprevir-based treatment arms. Each prior response category contained a different proportion of patients that experienced a less than 1 log10 reduction in HCV RNA at week 4 of the delayed start (lead-in) arm, but SVR rates among these subgroups also varied by prior response category. These data suggest that prior treatment response is a better predictor of SVR than a 1 log10 reduction at week 4 and that prospectively defined null responders and those patients with a less than 1 log10 reduction in HCV RNA at week 4 of a lead-in represent different patient populations.
About the Telaprevir Development Program
To date, more than 2,500 people with hepatitis C have received telaprevir-based therapy as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE studies. Together, these studies enrolled people with genotype 1 hepatitis C who had not been treated for their disease previously (ADVANCE and ILLUMINATE) as well as people who had been treated before but did not achieve a viral cure (REALIZE). A fact sheet on the Phase 3 telaprevir development program is available at http://www.vrtx.com/aasld2010.html
Phase 3 ADVANCE Trial
The pivotal Phase 3 ADVANCE study evaluated telaprevir-based response-guided regimens in 1,095 treatment-naïve patients. The primary endpoint of ADVANCE was SVR, defined as the proportion of people who had undetectable HCV RNA both at the end of treatment and 24 weeks after the end of treatment. The secondary endpoint was to evaluate the safety of telaprevir when dosed in combination with pegylated-interferon and ribavirin. As part of a response-guided design, people in the telaprevir-based treatment arms who had undetectable HCV RNA at weeks 4 and 12 of treatment were eligible to receive a total of 24 weeks therapy. Patients who did not meet the response-guided criterion but were undetectable at week 24, received 48 weeks of total therapy.
Phase 3 ILLUMINATE Trial
The ILLUMINATE trial was a supplemental Phase 3 study designed to evaluate whether there was any benefit in extending therapy from 24 to 48 weeks in people whose hepatitis C was undetectable at weeks 4 and 12 of therapy. The primary endpoint of the study was the proportion of people who achieved SVR in the randomized treatment groups, evaluated by a non-inferiority analysis.
Phase 3 REALIZE Trial
REALIZE was the second pivotal Phase 3 trial and was designed to evaluate telaprevir-based regimens in people who had received pegylated-interferon-based therapy but did not achieve a cure. REALIZE is the only Phase 3 clinical trial to date of an investigational direct-acting antiviral to include all major subgroups of difficult-to-treat patients including null responders, who were defined as people who had a less than a 2 log10 reduction in viral load by week 12 of a prior course of therapy.
Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the liver and blood of people with the disease.2 According to a 2010 report from the Institute of Medicine, up to 3.9 million people in the United States have chronic hepatitis C and 75% of those infected are unaware of their infection.3 Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved treatment regimen, do not achieve SVR, 4,5,6 or viral cure.1
Hepatitis C is spread through direct contact with the blood of infected people.2 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.2 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.2 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8,9,10,11 In the United States, hepatitis C is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.8 The majority of people with hepatitis C were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.11 By 2029, total annual medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.11
Additional resources for media, including a hepatitis C backgrounder and glossary of common terms, are available at: http://investors.vrtx.com/press.cfm
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with other pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer and pain.
Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
PEGASYS® and COPEGUS® are a registered trademarks of Hoffman-La Roche.
References:
1 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
2 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010.
3 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed May 25, 2010.
4 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
5 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
6 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
7 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
8 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected
persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.
9 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
10 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
11 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. This report was commissioned by Vertex Pharmaceuticals, Inc.
12 Picchio G, et al. Discrepancies between definitions of null response to treatment with peginterferon alfa-2a and ribavirin: Implications for new HCV drug development. [poster 289]. In: Program and Abstracts of the 2010 International Liver Conference by the European Association for the Study of Liver Disease. . Athens, Greece: April 2010.
13 United States Food and Drug Administration. Chronic hepatitis C virus infection: developing direct-acting antiviral agents for treatment. http://www.federalregister.gov/articles/2010/09/14/2010-22806/draft-guidance-for-industry-on-chronic-hepatitis-c-virus-infection-developing-directacting-antiviral. Updated September 14, 2010. Accessed September 14, 2010.
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements, including statements regarding (i) the data from ILLUMINATE being extremely promising and (ii) the expectation that the Company’s NDA for telaprevir will be completed in the fourth quarter of 2010. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that Vertex could experience unforeseen delays in submitting the NDA for telaprevir and/or obtaining approval to market telaprevir; that there may be varying interpretations of the data from the telaprevir clinical trials; that future outcomes from clinical trials of telaprevir may not be favorable; and that future scientific, clinical, competitive or other market factors may adversely affect the potential for telaprevir-based combination therapy and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex’s website at http://www.vrtx.com/. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
(VRTX-GEN)
Source
Source:biowire
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced new data from its Phase 3 studies of people with genotype 1 chronic hepatitis C who have not been treated previously. In these studies, the majority of people achieved superior sustained viral response (SVR or viral cure) rates with a telaprevir-based combination regimen, compared to current therapies, regardless of race/ethnicity or stage of liver fibrosis (factors known to limit response to current hepatitis C treatments). Patients in the ADVANCE and ILLUMINATE studies were given telaprevir with pegylated-interferon and ribavirin for the first 12 weeks of the studies, followed by treatment with pegylated-interferon and ribavirin alone for a total of either 24 weeks or 48 weeks based on their response to treatment at weeks 4 and 12. Final data from the Phase 3 ADVANCE and ILLUMINATE studies are being presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), which takes place in Boston October 29 to November 2.
“In our Phase 3 program, starting people with 12 weeks of telaprevir-based combination therapy resulted in significant improvements in viral cure rates, regardless of race, extent of liver damage or experience with prior treatment,” said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. “The results of the ADVANCE and ILLUMINATE studies represent a major milestone in the development of telaprevir and offer hope for doctors and the millions of people living with hepatitis C who need new and more effective medicines.”
Vertex Pharmaceuticals Incorporated is developing telaprevir in collaboration with Tibotec and Mitsubishi Tanabe Pharma.
Results from ADVANCE & ILLUMINATE
Overall in ADVANCE, 75% of people treated with a telaprevir-based combination regimen for 12 weeks, followed by an additional 12 or 36 weeks of pegylated-interferon and ribavirin alone, achieved SVR, compared to 44% of people treated with 48 weeks of pegylated-interferon and ribavirin alone. New data from this study showed that 62% of African Americans/Blacks achieved SVR with telaprevir compared to 25% of African Americans/Blacks who were treated with pegylated-interferon and ribavirin alone. Additionally, 62% of people with advanced liver fibrosis or cirrhosis (scarring of the liver) achieved SVR with telaprevir compared to 33% who were treated with pegylated-interferon and ribavirin alone.
Response-guided therapy was used in ADVANCE, whereby patients whose virus was undetectable at weeks 4 and 12 of treatment with telaprevir-based therapy were eligible to reduce their treatment time by half – from 48 weeks to 24 weeks. ILLUMINATE was designed to confirm both the use of response-guided therapy and to evaluate whether there was any benefit in extending therapy from 24 weeks to 48 weeks in people who met these criteria. In ADVANCE and ILLUMINATE, 58% and 65% of people, respectively, met these criteria for 24-week total treatment. In ILLUMINATE there was no benefit in extending therapy to 48 weeks.
In ILLUMINATE, 72% of people overall achieved SVR with telaprevir-based therapy. New data from this study showed that 60% of African Americans/Blacks and 63% of people with advanced liver fibrosis or cirrhosis achieved SVR with telaprevir-based therapy in the overall study analysis. Of African Americans/Blacks whose virus was undetectable at weeks 4 and 12, 88% of people achieved SVR in both the 24-week and 48-week randomized treatment arms. There was no control arm of pegylated-interferon and ribavirin alone in ILLUMINATE.
The safety and tolerability profile of telaprevir was consistent in both trials, with low discontinuation rates of all drugs during the telaprevir treatment phase due to adverse events.
“Less than half of people with the most common form of hepatitis C - genotype 1- achieve a viral cure with currently approved medicines, and factors such as race and extent of liver fibrosis can further limit cure rates to less than a third,” said Ira Jacobson, M.D., Chief of the Division of Gastroenterology and Hepatology, at New York-Presbyterian Hospital/Weill Cornell Medical Center, and the Vincent Astor Distinguished Professor of Medicine at Weill Cornell Medical College. “After treatment with telaprevir-based combination therapy in the ADVANCE study, 75% of people overall achieved a viral cure. Importantly, 62% of African Americans/Blacks and people with extensive liver disease achieved a viral cure – nearly twice as many as those who received pegylated-interferon and ribavirin alone.”
“Many patients today are not motivated to begin hepatitis C therapy given the year-long treatment time and low cure rates with approved therapies,” said Kenneth Sherman, M.D., Ph.D., Professor of Medicine at the University of Cincinnati College of Medicine, Director of the Division of Digestive Diseases for UC Health. “Data from the ILLUMINATE study are extremely promising and showed that high viral cure rates and shorter treatment duration may be possible for the majority of people who have not been treated previously.”
Additional Data at AASLD
Results from the EXTEND study are also being presented at the meeting. EXTEND is a long-term follow-up study of patients who received telaprevir-based regimens in the PROVE Phase 2 clinical trials and was designed to evaluate whether people maintain their SVR (viral cure) over time and to observe changes in hepatitis C viral resistance variants in those telaprevir-treated patients who had not achieved SVR. The results showed that after an average of two years of follow-up, SVR rates with telaprevir were durable in 99% (122/123) of patients with SVR who took part in the trials. Among patients who did not achieve SVR and who had resistant variants at the start of the EXTEND study, 89% (50/56) no longer had detectable variants.
Safety & Tolerability Results from ADVANCE and ILLUMINATE
The safety and tolerability results of telaprevir-based combination regimens were consistent in the ADVANCE and ILLUMINATE studies. Treatment discontinuation rates of all drugs due to adverse events during the telaprevir treatment phase in the ADVANCE study were low in the telaprevir arms (7% to 8%) and the control arm (4%). The most common adverse events (>25% of people) reported in both studies, regardless of treatment arm, were rash, fatigue, pruritis, headache, nausea, anemia, insomnia, diarrhea, influenza-like symptoms and pyrexia. The majority of these adverse events were mild to moderate.
To optimize each patient’s opportunity to achieve viral cure in the Phase 3 studies, sequential discontinuation of the drugs was recommended if discontinuation of treatment was necessary due to adverse events. Investigators were not required to discontinue the use of all three drugs at once, and, for example, patients may have continued on pegylated-interferon and ribavirin after discontinuing telaprevir only.
In ADVANCE, discontinuation of telaprevir or placebo only due to adverse events during the telaprevir treatment phase occurred in 11% of people in the 12-week telaprevir arm, 7% of people in the 8-week telaprevir arm and 1% of people in the control arm. In ILLUMINATE, 12% of people overall discontinued telaprevir only due to adverse events during the telaprevir treatment phase.
Discontinuation of all drugs due to either rash or anemia was low in both studies (1% to 3%). Rash was primarily characterized as eczema-like, manageable and resolved upon stopping telaprevir. Ninety-two percent and 95% of rash was mild to moderate in ADVANCE and ILLUMINATE, respectively. Rash was managed with the use of topical corticosteroids and antihistamines, and anemia was primarily managed by reducing the dose of ribavirin. The use of erythropoiesis-stimulating agents (ESAs) were not allowed in any of the Phase 3 clinical studies.
Planned NDA Submission and Additional Phase 3 Analysis
Three Phase 3 studies, ADVANCE, ILLUMINATE and REALIZE will form the basis of the clinical portion of the telaprevir New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA), which is expected to be complete in the fourth quarter of 2010. REALIZE evaluated telaprevir in three groups of people with genotype 1 hepatitis C who did not achieve a viral cure with previous treatment: (1) those who relapsed, (2) those who achieved a partial response and (3) those who had a null response to prior treatment (<2 log10 reduction in HCV RNA at week 12). Topline results from REALIZE were reported in a press release on September 7, 2010.
At a 2010 medical meeting,Vertex’s collaborator Tibotec reported results on the correlation of poor interferon response (<1 log10 reduction in HCV RNA at week 4) with the standard definition for null response (< 2 log10 reduction in HCV RNA at week 12).12,13 In these results, 38% (9/24) of patients who had a less than 1 log10 response at week 4 subsequently had a greater than 2 log10 reduction in HCV RNA at week 12. This analysis suggested that some patients would be misclassified as null responders using the definition of a less than 1 log10 reduction in HCV RNA at week 4.
An additional sub-analysis in the REALIZE study showed that among the combined partial responder and relapser patients in the telaprevir delayed start (lead-in) arm of the REALIZE study, 18% (31/171) had a less than 1 log10 reduction in HCV RNA at week 4 and of these patients, 58% (18/31) achieved SVR compared to 31% (46/147) of patients prospectively-defined as prior null responders (<2 log10 at week 12) in the combined telaprevir-based treatment arms. Each prior response category contained a different proportion of patients that experienced a less than 1 log10 reduction in HCV RNA at week 4 of the delayed start (lead-in) arm, but SVR rates among these subgroups also varied by prior response category. These data suggest that prior treatment response is a better predictor of SVR than a 1 log10 reduction at week 4 and that prospectively defined null responders and those patients with a less than 1 log10 reduction in HCV RNA at week 4 of a lead-in represent different patient populations.
About the Telaprevir Development Program
To date, more than 2,500 people with hepatitis C have received telaprevir-based therapy as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE studies. Together, these studies enrolled people with genotype 1 hepatitis C who had not been treated for their disease previously (ADVANCE and ILLUMINATE) as well as people who had been treated before but did not achieve a viral cure (REALIZE). A fact sheet on the Phase 3 telaprevir development program is available at http://www.vrtx.com/aasld2010.html
Phase 3 ADVANCE Trial
The pivotal Phase 3 ADVANCE study evaluated telaprevir-based response-guided regimens in 1,095 treatment-naïve patients. The primary endpoint of ADVANCE was SVR, defined as the proportion of people who had undetectable HCV RNA both at the end of treatment and 24 weeks after the end of treatment. The secondary endpoint was to evaluate the safety of telaprevir when dosed in combination with pegylated-interferon and ribavirin. As part of a response-guided design, people in the telaprevir-based treatment arms who had undetectable HCV RNA at weeks 4 and 12 of treatment were eligible to receive a total of 24 weeks therapy. Patients who did not meet the response-guided criterion but were undetectable at week 24, received 48 weeks of total therapy.
Phase 3 ILLUMINATE Trial
The ILLUMINATE trial was a supplemental Phase 3 study designed to evaluate whether there was any benefit in extending therapy from 24 to 48 weeks in people whose hepatitis C was undetectable at weeks 4 and 12 of therapy. The primary endpoint of the study was the proportion of people who achieved SVR in the randomized treatment groups, evaluated by a non-inferiority analysis.
Phase 3 REALIZE Trial
REALIZE was the second pivotal Phase 3 trial and was designed to evaluate telaprevir-based regimens in people who had received pegylated-interferon-based therapy but did not achieve a cure. REALIZE is the only Phase 3 clinical trial to date of an investigational direct-acting antiviral to include all major subgroups of difficult-to-treat patients including null responders, who were defined as people who had a less than a 2 log10 reduction in viral load by week 12 of a prior course of therapy.
Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the liver and blood of people with the disease.2 According to a 2010 report from the Institute of Medicine, up to 3.9 million people in the United States have chronic hepatitis C and 75% of those infected are unaware of their infection.3 Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved treatment regimen, do not achieve SVR, 4,5,6 or viral cure.1
Hepatitis C is spread through direct contact with the blood of infected people.2 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.2 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.2 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8,9,10,11 In the United States, hepatitis C is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.8 The majority of people with hepatitis C were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.11 By 2029, total annual medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.11
Additional resources for media, including a hepatitis C backgrounder and glossary of common terms, are available at: http://investors.vrtx.com/press.cfm
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with other pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer and pain.
Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
PEGASYS® and COPEGUS® are a registered trademarks of Hoffman-La Roche.
References:
1 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
2 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010.
3 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed May 25, 2010.
4 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
5 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
6 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
7 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
8 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected
persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.
9 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
10 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
11 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. This report was commissioned by Vertex Pharmaceuticals, Inc.
12 Picchio G, et al. Discrepancies between definitions of null response to treatment with peginterferon alfa-2a and ribavirin: Implications for new HCV drug development. [poster 289]. In: Program and Abstracts of the 2010 International Liver Conference by the European Association for the Study of Liver Disease. . Athens, Greece: April 2010.
13 United States Food and Drug Administration. Chronic hepatitis C virus infection: developing direct-acting antiviral agents for treatment. http://www.federalregister.gov/articles/2010/09/14/2010-22806/draft-guidance-for-industry-on-chronic-hepatitis-c-virus-infection-developing-directacting-antiviral. Updated September 14, 2010. Accessed September 14, 2010.
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements, including statements regarding (i) the data from ILLUMINATE being extremely promising and (ii) the expectation that the Company’s NDA for telaprevir will be completed in the fourth quarter of 2010. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that Vertex could experience unforeseen delays in submitting the NDA for telaprevir and/or obtaining approval to market telaprevir; that there may be varying interpretations of the data from the telaprevir clinical trials; that future outcomes from clinical trials of telaprevir may not be favorable; and that future scientific, clinical, competitive or other market factors may adversely affect the potential for telaprevir-based combination therapy and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex’s website at http://www.vrtx.com/. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
(VRTX-GEN)
Source
Black patients fare well on Vertex hepatitis C drug
By Bill Berkrot
NEW YORK
Sat Oct 30, 2010 2:12pm BST
NEW YORK (Reuters) - A closer look at data from a late stage trial of Vertex Pharmaceuticals Inc's eagerly anticipated hepatitis C drug telaprevir showed impressive cure rates for black patients and for patients with advanced liver disease.
In the Phase III study known as Advance, 62 percent of black patients who received telaprevir achieved sustained viral response (SVR), which is considered tantamount to a cure. That compared with just a 25 percent cure rate from the current standard drugs of pegylated interferon and ribavirin.
"If you look at that treatment difference and then you look at the difference in the overall population, in fact the benefit relatively speaking is even greater," Robert Kauffman, Vertex's chief medical officer, said in a telephone interview.
"Obviously, from an absolute point of view it's still a little bit lesser response," he said.
The study's overall cure rates -- 75 percent for telaprevir in combination with the current standard drugs versus 44 percent for the standard drugs alone -- was previously released. But full details of the trial were being presented for the first time at the American Association for the Study of Liver Diseases meeting in Boston.
Breaking out an analysis of black patients in the trial was significant because of the greater prevalence of hepatitis C and historically lower cure rates for that population.
"African Americans bare a large proportion of the burden of hepatitis C in the United States" compared with Caucasians and the overall general population, Kauffman said.
According to data compiled from 1999 to 2002, one in seven African American men between the ages of 50 and 59 in the United States is living with hepatitis C.
Telaprevir, from a new class of antiviral drugs, is widely expected to be approved by U.S. regulators next year. Vertex plans to complete its application seeking approval this year.
Excitement has been high over the drug, and a similar experimental medicine being developed by Merck & Co, because they have demonstrated significantly higher cure rates than current drugs and the potential to cut treatment duration in half for many patients.
Cutting treatment duration from the current 48 weeks is a huge advantage as the current drugs, which must still be taken with the new medicines, can cause debilitating flu-like symptoms that cause many patients to discontinue treatment or avoid it altogether. It is believed that thousands of patients with hepatitis C have been putting off treatment to await the new, more effective medicines.
In the Advance study, 58 percent of patients who received telaprevir met the criteria for a 24-week treatment duration. That criteria called for levels of the virus in the blood to fall to undetectable levels after four and 12 weeks of treatment.
A separate study demonstrated no additional benefit from extending telaprevir treatment to the full 48 weeks in patients who met the criteria for shorter duration treatment.
A further sub-group analysis of the Advance data showed that telaprevir led to a 62 percent cure rate in hepatitis C patients with advanced liver fibrosis or cirrhosis compared with a 33 percent SVR rate on standard drugs. Patients with those conditions, which can lead to liver cancer or need for a transplant, are also traditionally more difficult to treat than the overall hepatitis C population.
"In our Phase III program, starting people with 12 weeks of telaprevir-based combination therapy resulted in significant improvements in viral cure rates, regardless of race, extent of liver damage or experience with prior treatment," Kauffman said.
(Reporting by Bill Berkrot; Editing by Bernard Orr)
Source
NEW YORK
Sat Oct 30, 2010 2:12pm BST
NEW YORK (Reuters) - A closer look at data from a late stage trial of Vertex Pharmaceuticals Inc's eagerly anticipated hepatitis C drug telaprevir showed impressive cure rates for black patients and for patients with advanced liver disease.
In the Phase III study known as Advance, 62 percent of black patients who received telaprevir achieved sustained viral response (SVR), which is considered tantamount to a cure. That compared with just a 25 percent cure rate from the current standard drugs of pegylated interferon and ribavirin.
"If you look at that treatment difference and then you look at the difference in the overall population, in fact the benefit relatively speaking is even greater," Robert Kauffman, Vertex's chief medical officer, said in a telephone interview.
"Obviously, from an absolute point of view it's still a little bit lesser response," he said.
The study's overall cure rates -- 75 percent for telaprevir in combination with the current standard drugs versus 44 percent for the standard drugs alone -- was previously released. But full details of the trial were being presented for the first time at the American Association for the Study of Liver Diseases meeting in Boston.
Breaking out an analysis of black patients in the trial was significant because of the greater prevalence of hepatitis C and historically lower cure rates for that population.
"African Americans bare a large proportion of the burden of hepatitis C in the United States" compared with Caucasians and the overall general population, Kauffman said.
According to data compiled from 1999 to 2002, one in seven African American men between the ages of 50 and 59 in the United States is living with hepatitis C.
Telaprevir, from a new class of antiviral drugs, is widely expected to be approved by U.S. regulators next year. Vertex plans to complete its application seeking approval this year.
Excitement has been high over the drug, and a similar experimental medicine being developed by Merck & Co, because they have demonstrated significantly higher cure rates than current drugs and the potential to cut treatment duration in half for many patients.
Cutting treatment duration from the current 48 weeks is a huge advantage as the current drugs, which must still be taken with the new medicines, can cause debilitating flu-like symptoms that cause many patients to discontinue treatment or avoid it altogether. It is believed that thousands of patients with hepatitis C have been putting off treatment to await the new, more effective medicines.
In the Advance study, 58 percent of patients who received telaprevir met the criteria for a 24-week treatment duration. That criteria called for levels of the virus in the blood to fall to undetectable levels after four and 12 weeks of treatment.
A separate study demonstrated no additional benefit from extending telaprevir treatment to the full 48 weeks in patients who met the criteria for shorter duration treatment.
A further sub-group analysis of the Advance data showed that telaprevir led to a 62 percent cure rate in hepatitis C patients with advanced liver fibrosis or cirrhosis compared with a 33 percent SVR rate on standard drugs. Patients with those conditions, which can lead to liver cancer or need for a transplant, are also traditionally more difficult to treat than the overall hepatitis C population.
"In our Phase III program, starting people with 12 weeks of telaprevir-based combination therapy resulted in significant improvements in viral cure rates, regardless of race, extent of liver damage or experience with prior treatment," Kauffman said.
(Reporting by Bill Berkrot; Editing by Bernard Orr)
Source
Achieving Sustained Viral Response for Patients with Recurrent Hepatitis C After Transplantation is Key for Long-Term Outcomes
Presented: Sunday, October 31, 8:45 am Eastern Time
BOSTON, Oct. 30 /PRNewswire/ -- Researchers from the University of Bari, Italy, concluded that treating patients after transplantation with antiviral therapy creates a sustained viral response (SVR) and protects them from liver-related deaths. The purpose of this study was to determine the long-term clinical outcomes of patients posttransplant who underwent antiviral therapy for recurrent hepatitis C virus (HCV) infection of the liver graft.
The use in clinical practice of antiviral therapy for HCV recurrence after liver transplantation is still controversial. Some favor antiviral therapy while data coming from meta-analysis of published studies do not recommend treatment in view of the frequent adverse effects and the lack of clinical benefit.
Maria Rendina, MD, on behalf of the AISF RECOLT-C Group, examined the records from 12 liver transplant centers in Italy over a 20-year period, and showed data on SVR and long-term clinical outcomes for a large posttransplantation patient population.
SVR was achieved in 35 percent of the 448 patients whose records were included in this study. Researchers noted that patients who achieved SVR received grafts from younger donors, received longer treatment duration and cumulative dose of interferon, and had a lower drop-out rate and lower incidence of diabetes; however there were no differences in immunosuppressive strategy for these patients.
Of the 134 patients who died since transplantation, 73 percent of those deaths were HCV related – and only one of those patients was able to achieve SVR. After univariate and multivariate analysis to correct for other variables, researchers demonstrated that patients with recurrent HCV who were unable to achieve SVR were at a high risk for liver-related deaths.
According to Dr. Rendina: "The results of the study are important as these data could have an impact on patient care: HCV viral eradication significantly protects patients from liver-related death and, therefore, must be strongly pursued. When asked about the future of research in this area, Dr. Rendina said, "Data from the AISF RECOLT-C Group provide a direction for further randomized clinical trials aimed at exploring various treatment options as well as the efficacy of new antivirals."
Abstract title:
SVR to antiviral therapy is highly protective against liver-related death in patients with HCV recurrence on the graft after liver transplantation (LT)
About the AASLD
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Boston, Massachusetts, October 29-November 2, will bring together more than 7,500 researchers from 55 countries.
A pressroom will be available from October 30 at the annual meeting. For copies of abstracts and press releases, or to arrange for pre-conference research interviews contact Gregory Bologna at 703-299-9766. To pre-register, call Ann Haran at 703-299-9766.
Press releases and all abstracts are available online at http://www.aasld.org/.
Media Contact: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: October 30 – November 2, 2010
Hynes Convention Center, Room 208
Telephone: 617-954-3106
Researcher: Maria Rendina, MD
University of Bari, Italy
Email: mrendina@yahoo.com
Source
BOSTON, Oct. 30 /PRNewswire/ -- Researchers from the University of Bari, Italy, concluded that treating patients after transplantation with antiviral therapy creates a sustained viral response (SVR) and protects them from liver-related deaths. The purpose of this study was to determine the long-term clinical outcomes of patients posttransplant who underwent antiviral therapy for recurrent hepatitis C virus (HCV) infection of the liver graft.
The use in clinical practice of antiviral therapy for HCV recurrence after liver transplantation is still controversial. Some favor antiviral therapy while data coming from meta-analysis of published studies do not recommend treatment in view of the frequent adverse effects and the lack of clinical benefit.
Maria Rendina, MD, on behalf of the AISF RECOLT-C Group, examined the records from 12 liver transplant centers in Italy over a 20-year period, and showed data on SVR and long-term clinical outcomes for a large posttransplantation patient population.
SVR was achieved in 35 percent of the 448 patients whose records were included in this study. Researchers noted that patients who achieved SVR received grafts from younger donors, received longer treatment duration and cumulative dose of interferon, and had a lower drop-out rate and lower incidence of diabetes; however there were no differences in immunosuppressive strategy for these patients.
Of the 134 patients who died since transplantation, 73 percent of those deaths were HCV related – and only one of those patients was able to achieve SVR. After univariate and multivariate analysis to correct for other variables, researchers demonstrated that patients with recurrent HCV who were unable to achieve SVR were at a high risk for liver-related deaths.
According to Dr. Rendina: "The results of the study are important as these data could have an impact on patient care: HCV viral eradication significantly protects patients from liver-related death and, therefore, must be strongly pursued. When asked about the future of research in this area, Dr. Rendina said, "Data from the AISF RECOLT-C Group provide a direction for further randomized clinical trials aimed at exploring various treatment options as well as the efficacy of new antivirals."
Abstract title:
SVR to antiviral therapy is highly protective against liver-related death in patients with HCV recurrence on the graft after liver transplantation (LT)
About the AASLD
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Boston, Massachusetts, October 29-November 2, will bring together more than 7,500 researchers from 55 countries.
A pressroom will be available from October 30 at the annual meeting. For copies of abstracts and press releases, or to arrange for pre-conference research interviews contact Gregory Bologna at 703-299-9766. To pre-register, call Ann Haran at 703-299-9766.
Press releases and all abstracts are available online at http://www.aasld.org/.
Media Contact: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: October 30 – November 2, 2010
Hynes Convention Center, Room 208
Telephone: 617-954-3106
Researcher: Maria Rendina, MD
University of Bari, Italy
Email: mrendina@yahoo.com
Source
Boehringer Ingelheim Oral Hepatitis C Protease Inhibitor and Polymerase Inhibitor Combination Shows Rapid Viral Response without Use of Pegylated Interferon
BusinessWire · Saturday, Oct. 30, 2010
Boehringer Ingelheim announced results from a Phase Ib study, SOUND-C1, that showed the combination of two oral hepatitis C virus (HCV) compounds, the protease inhibitor BI 201335 and the polymerase inhibitor BI 207127, with ribavirin reduced viral load to the lower limit of quantifiable levels in HCV treatment-naïve patients. The regimen did not include interferon through the first 28 days of treatment. These data are being presented at the American Association for the Study of Liver Diseases (AASLD) 2010 Liver Meeting in Boston, MA.
(Poster LB-7) New protease-polymerase inhibitor combination resulted in 73-100%rapid virological responses without pegylated interferon
In this randomised open-label trial, 32 treatment-naïve genotype-1 HCV patients received a combination of BI 207127 in either 400mg or 600mg doses three times a day (TID) with BI 201335 120mg once daily (QD) together with ribavirin (RBV) (1000/1200mg daily in two doses) for 28 days. All patients had a rapid and sharp decline in HCV viral load during the first two days, followed by a slower second phase decline. In the lower and higher dose groups, 73 and 100% of patients achieved a rapid virological response (i.e. had a HCV RNA below thelower limit of quantification after 4 weeks of treatment). One patient experienced a viral breakthrough (increase by >1 LOG10 from nadir during treatment) and one other experienced a 0.7 LOG10 increase in viral load. Both patients were in the lower dose group of BI 207127 and were patients with a high baseline viral load. On day 29, all patients were switched to treatment with BI 201335 and PegIFN/RBV for an additional 44 weeks per the defined study protocol, and will be followed to evaluate sustained virological response.
“These early data suggest that there is the potential for the combination of oral anti-HCV therapies to reduce the viral load in a more tolerable, interferon-sparing regimen. The current standard-of-care, PegIFN/RBV, is challenging for HCV patients due to side effects that impact treatment adherence and has suboptimal response rates,” said Stefan Zeuzem, MD, Chief of the Department of Medicine and Professor of Medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany and lead investigator of the study. “An interferon-sparing regimen could provide an important treatment option for patients with chronic hepatitis C.”
The PegIFN sparing treatment was well tolerated. Investigators reported that the most common adverse events observed in the study were mild gastro-intestinal effects (diarrhea, nausea, vomiting), rash or photosensitivity. Laboratory parameters did not indicate any relevant changes from baseline, except for a continuous drop in amino alanine transferase (ALT) in all patients, a decrease of hemoglobin (median -1.7 and -2.6 g/dL) and an increase of unconjugated bilirubin (median +9.8 and +11.5 umol/L) similar to reported results from earlier BI 201335 trials. There were no serious or severe adverse events and no discontinuations due to adverse events reported in the study during treatment with BI 207127 and BI 201335. A phase IIb trial testing different dose regimens of this combination with longer durations is planned to evaluate sustained virological response rates.
Additional studies to be presented at AASLD
• Virological response and safety of 4 weeks treatment with the protease inhibitor BI 201335 combined with 48 weeks of peginterferon alpha 2a and ribavirin for treatment of HCV GT-1 patients who failed peginterferon / ribavirin
(Poster 804. T. Berg, et al. Sun, October 31 - 8:00 AM. Hynes: Exhibit Hall C)
• Genotypic and phenotypic analysis of the NS5B polymerase region from viral isolates of HCV chronically infected patients treated with BI 207127 for 5-days monotherapy.
(Poster 1862. L. Lagace, et al. Tue, November 2 - 7:00 AM. Hynes: Exhibit Hall C)
• The Liver Kp Corrected Inhibitory Quotient (LCIQ): A pharmacokinetic-pharmacodynamic model for direct-acting HCV antivirals
(Poster 1866. J. Duan, et al. Tue, 2 November 2 – 7:00 AM. Hynes: Exhibit Hall C)
About Hepatitis C Virus (HCV)
HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant. The number of individuals chronically infected with HCV globally has been estimated at 170 million, with 3–4 million new infections occurring each year. Only about 20–45% of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20% will develop cirrhosis within a mean of 20 years. The mortality rate after cirrhosis has developed is 2-5% per year. End-stage liver disease due to HCV infection currently represents the major indication for liver transplantation in the Western world.
About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research program for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV (VIRAMUNE® (nevirapine) tablets/oral solution, the first approved HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) and Aptivus®, an HIV protease inhibitor). The company has a well established research centre in Laval, Canada, dedicated to virology research since the early 1990’s, and is committed to developing new therapies for virological diseases with a high unmet medical need.
Boehringer Ingelheim in Hepatitis C Virus (HCV)
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim’s own research and development, which has completed clinical trials through Phase IIb (SILEN-C studies). This Phase II program supports the investigation of BI 201335 in Phase III trials. BI 207127 is an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Planning is currently underway to begin Phase II trials of BI 207127 with BI 201335 in interferon-sparing regimens both with and without ribavirin.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
For more information, please visit http://www.boehringer-ingelheim.com/
Contacts
Julia Meyer-Kleinmann
Director Corporate Communications
Boehringer Ingelheim GmbH
55216 Ingelheim/Germany
Phone: + 49 - 6132 – 77 8271
Fax: + 49 - 6132 – 77 70 77
E-mail: press@boehringer-ingelheim.com
Source
Boehringer Ingelheim announced results from a Phase Ib study, SOUND-C1, that showed the combination of two oral hepatitis C virus (HCV) compounds, the protease inhibitor BI 201335 and the polymerase inhibitor BI 207127, with ribavirin reduced viral load to the lower limit of quantifiable levels in HCV treatment-naïve patients. The regimen did not include interferon through the first 28 days of treatment. These data are being presented at the American Association for the Study of Liver Diseases (AASLD) 2010 Liver Meeting in Boston, MA.
(Poster LB-7) New protease-polymerase inhibitor combination resulted in 73-100%rapid virological responses without pegylated interferon
In this randomised open-label trial, 32 treatment-naïve genotype-1 HCV patients received a combination of BI 207127 in either 400mg or 600mg doses three times a day (TID) with BI 201335 120mg once daily (QD) together with ribavirin (RBV) (1000/1200mg daily in two doses) for 28 days. All patients had a rapid and sharp decline in HCV viral load during the first two days, followed by a slower second phase decline. In the lower and higher dose groups, 73 and 100% of patients achieved a rapid virological response (i.e. had a HCV RNA below thelower limit of quantification after 4 weeks of treatment). One patient experienced a viral breakthrough (increase by >1 LOG10 from nadir during treatment) and one other experienced a 0.7 LOG10 increase in viral load. Both patients were in the lower dose group of BI 207127 and were patients with a high baseline viral load. On day 29, all patients were switched to treatment with BI 201335 and PegIFN/RBV for an additional 44 weeks per the defined study protocol, and will be followed to evaluate sustained virological response.
“These early data suggest that there is the potential for the combination of oral anti-HCV therapies to reduce the viral load in a more tolerable, interferon-sparing regimen. The current standard-of-care, PegIFN/RBV, is challenging for HCV patients due to side effects that impact treatment adherence and has suboptimal response rates,” said Stefan Zeuzem, MD, Chief of the Department of Medicine and Professor of Medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany and lead investigator of the study. “An interferon-sparing regimen could provide an important treatment option for patients with chronic hepatitis C.”
The PegIFN sparing treatment was well tolerated. Investigators reported that the most common adverse events observed in the study were mild gastro-intestinal effects (diarrhea, nausea, vomiting), rash or photosensitivity. Laboratory parameters did not indicate any relevant changes from baseline, except for a continuous drop in amino alanine transferase (ALT) in all patients, a decrease of hemoglobin (median -1.7 and -2.6 g/dL) and an increase of unconjugated bilirubin (median +9.8 and +11.5 umol/L) similar to reported results from earlier BI 201335 trials. There were no serious or severe adverse events and no discontinuations due to adverse events reported in the study during treatment with BI 207127 and BI 201335. A phase IIb trial testing different dose regimens of this combination with longer durations is planned to evaluate sustained virological response rates.
Additional studies to be presented at AASLD
• Virological response and safety of 4 weeks treatment with the protease inhibitor BI 201335 combined with 48 weeks of peginterferon alpha 2a and ribavirin for treatment of HCV GT-1 patients who failed peginterferon / ribavirin
(Poster 804. T. Berg, et al. Sun, October 31 - 8:00 AM. Hynes: Exhibit Hall C)
• Genotypic and phenotypic analysis of the NS5B polymerase region from viral isolates of HCV chronically infected patients treated with BI 207127 for 5-days monotherapy.
(Poster 1862. L. Lagace, et al. Tue, November 2 - 7:00 AM. Hynes: Exhibit Hall C)
• The Liver Kp Corrected Inhibitory Quotient (LCIQ): A pharmacokinetic-pharmacodynamic model for direct-acting HCV antivirals
(Poster 1866. J. Duan, et al. Tue, 2 November 2 – 7:00 AM. Hynes: Exhibit Hall C)
About Hepatitis C Virus (HCV)
HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant. The number of individuals chronically infected with HCV globally has been estimated at 170 million, with 3–4 million new infections occurring each year. Only about 20–45% of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20% will develop cirrhosis within a mean of 20 years. The mortality rate after cirrhosis has developed is 2-5% per year. End-stage liver disease due to HCV infection currently represents the major indication for liver transplantation in the Western world.
About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research program for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV (VIRAMUNE® (nevirapine) tablets/oral solution, the first approved HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) and Aptivus®, an HIV protease inhibitor). The company has a well established research centre in Laval, Canada, dedicated to virology research since the early 1990’s, and is committed to developing new therapies for virological diseases with a high unmet medical need.
Boehringer Ingelheim in Hepatitis C Virus (HCV)
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim’s own research and development, which has completed clinical trials through Phase IIb (SILEN-C studies). This Phase II program supports the investigation of BI 201335 in Phase III trials. BI 207127 is an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Planning is currently underway to begin Phase II trials of BI 207127 with BI 201335 in interferon-sparing regimens both with and without ribavirin.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
For more information, please visit http://www.boehringer-ingelheim.com/
Contacts
Julia Meyer-Kleinmann
Director Corporate Communications
Boehringer Ingelheim GmbH
55216 Ingelheim/Germany
Phone: + 49 - 6132 – 77 8271
Fax: + 49 - 6132 – 77 70 77
E-mail: press@boehringer-ingelheim.com
Source
Salix Pharmaceuticals Previews Data Slated for Presentation at 61st Annual Meeting of the American Association for the Study of Liver Diseases
Oct. 30, 2010, 9:00 a.m. EDT
BOSTON, Oct 30, 2010 (BUSINESS WIRE) -- Salix Pharmaceuticals, Inc. /quotes/comstock/15*!slxp/quotes/nls/slxp (SLXP 37.83, +0.41, +1.10%) today announced that the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010) will be an important venue for ongoing discussion of hepatic encephalopathy, or HE. Numerous posters and oral presentations provide insight regarding HE's burden on patients, caregivers and the healthcare system; the earlier identification and diagnosis of HE; the growing recognition of the importance of aggressive management of HE; and the use of XIFAXAN(R) (rifaximin) 550 mg for the reduction in risk of overt HE recurrence.
"In the last decade, HE-related hospitalizations have more than doubled. Today, an estimated one third to one half of all hospitalizations in cirrhotic patients are partially or wholly attributable to hepatic encephalopathy," stated Bill Forbes, Executive Vice President, Research and Development and Chief Development Officer, Salix, "Hepatic encephalopathy signifies a poor prognosis with one-year and three-year mortality rates of 58 percent and 77 percent, respectively, after presentation of the first episode of acute HE. The introduction of XIFAXAN 550 mg, the first new therapy approved for HE in 30 years, is providing physicians a much-needed therapy to manage their patients and to help patients break the cycle of relapse. Additionally, the availability of this tolerable and efficacious treatment for overt HE has re-energized the HE research community and challenged physicians to more aggressively approach HE therapy with the intention of improving treatment success and long-term outcomes."
Rifaximin-Related Presentations at AASLD
Oral Presentation #24: Leise et al. "Impact of Rifaximin Treatment on Survival in Patients with End-stage Liver Disease." Sunday, Oct. 31, 2010, 1:00 - 2:30 p.m., Hynes, Room 312
This analysis compared the long term effect of rifaximin by comparing survival in HE patients receiving rifaximin (long-term open label trial) versus patients awaiting liver transplantation (Organ Procurement and Transplant network).
Oral Presentation #19: Vlachogiannakos et al. "Long-term Administration of Rifaximin Improves the Prognosis of Patients with Alcohol-related Decompensated Cirrhosis: A Case-control study." Sunday, Oct. 31, 2010, 1:00 - 2:30 pm, Hynes, Room 312
This study evaluated the effect of intestinal decontamination with rifaximin (1200 mg for 4 weeks) on the long-term prognosis of 23 patients with alcohol-related decompensated cirrhosis and ascites. Five-year cumulative probability of survival data were obtained.
Oral Presentation #22: Bajaj et al. "Rifaximin Improves Driving Simulator Performance in Minimal Hepatic Encephalopathy: A Double-blind, Placebo-controlled, Prospective Randomized Trial." Sunday, Oct. 31, 2010, 1:00 - 2:30 p.m., Hynes, Room 312
A total of 42 MHE patients, diagnosed using a battery of five tests of cognitive function (CB) and without overt HE, participated in the eight-week trial. Patients initially underwent a baseline evaluation of driving and navigation simulation (outcomes were speeding tickets, collisions and illegal turns), Quality of Life with Sickness Impact Profile (SIP, which includes physical/psycho-social scores), ammonia and model for end-stage liver disease (MELD) score, in addition to the CB. Patients were randomized to receive XIFAXAN 550 mg or placebo twice-daily (BID) (n=21 in each group). All evaluations were repeated at the eight-week visit. The primary outcomes were proportion improved in speeding, illegal turns and collisions; secondary outcomes were proportion improved in mean CB Zscores and SIP scores. In addition to being presented at AASLD, this study was recently published in Gastroenterology.
Poster #1192: Krag et. al. "Systematic Review and Meta-analyses of Randomised Trials on Ammonia lowering Regimens for Hepatic Encephalopathy." Monday, Nov. 1, 2010, 8:00 a.m. - 5:30 p.m., Hynes, Exhibit Hall C.
These meta-analyses of 21 randomized trials evaluated the effects of ammonia lowering interventions in the management of hepatic encephalopathy.
About Hepatic Encephalopathy
Hepatic encephalopathy (HE) is a disorder caused by chronic liver failure resulting in cognitive, psychiatric and motor impairments.The condition encompasses a wide spectrum of often reversible neuropsychiatric abnormalities caused by the inability of the liver to remove toxic products in the gut from most notably ammonia-producing bacteria. When toxins reach the central nervous system, this condition can result in symptoms ranging in severity from mild cerebral function deficits to coma. The disorder is characterized by disruption in sleep patterns, changes in personality and intellectual capacity, high blood ammonia levels, altered neuromuscular activity and electroencephalogram (EEG) abnormalities.
About XIFAXAN(R) (rifaximin) 550 mg tablets
Important Safety Information
XIFAXAN 550 mg is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients greater-than or equal to 18 years of age. In the trials of XIFAXAN for HE, 91 percent of the patients were using lactulose concomitantly. XIFAXAN has not been studied in patients with MELD scores greater than 25, and only 8.6 percent of patients in the controlled trial had MELD scores over 19. There is increased systemic exposure in patients with more severe hepatic dysfunction. Therefore, caution should be exercised when administering XIFAXAN to patients with severe hepatic impairment (Child-Pugh C).
XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, any of the rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema and anaphylaxis.
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon which may lead to overgrowth of C. difficile. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
The most common adverse reactions occurring in greater than eight percent of patients in the clinical study were edema peripheral (15 percent), nausea (14 percent), dizziness (13 percent), fatigue (12 percent), ascites (11 percent), muscle spasms (nine percent), pruritus (nine percent) and abdominal pain (nine percent).
About XIFAXAN(R) (rifaximin) 200 mg tablets
Rifaximin is a gut-selective antibiotic with negligible systemic absorption and broad-spectrum activity in vitro against both Gram-positive and Gram-negative pathogens. Rifaximin has a similar tolerability profile to that of placebo.
Rifaximin tablets 200 mg, which Salix markets in the U.S. under the trade name XIFAXAN(R) (rifaximin) tablets 200 mg, currently is approved for the treatment of patients, 12 years of age or older, with travelers' diarrhea (TD) caused by non--invasive strains of Escherichia coli. XIFAXAN should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli. XIFAXAN should be discontinued if diarrhea symptoms get worse or persist more than 24--48 hours, and alternative antibiotic therapy should be considered. In clinical trials, XIFAXAN was generally well-tolerated. The most common side effects (versus placebo) were flatulence 11.3 percent (versus 19.7 percent), headache 9.7 percent (versus 9.2 percent), abdominal pain 7.2 percent (versus 10.1 percent) and rectal tenesmus 7.2 percent (versus 8.8 percent).
Rifaximin has been used in Italy for 24 years and is approved in 33 countries. Salix acquired rights to market rifaximin in North America from Alfa Wassermann S.p.A. in Bologna, Italy. Alfa Wassermann markets rifaximin in Italy under the trade name Normix(R).
About Salix Pharmaceuticals
Salix Pharmaceuticals, Ltd., headquartered in Raleigh, NC, develops and markets prescription pharmaceutical products for the treatment of gastrointestinal diseases. Salix's strategy is to in-license late-stage or marketed proprietary therapeutic drugs, complete with any required development and regulatory submission of these products, and market them through the Company's gastroenterology specialty sales and marketing team.
Salix also markets MOVIPREP(R) (PEG 3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution), OSMOPREP(R) (sodium phosphate monobasic monohydrate, USP and sodium phosphate dibasic anhydrous, USP) Tablets, VISICOL(R) (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets, APRISO(TM) (mesalamine) extended-release capsules 0.375 g., METOZOLV(R) ODT (metoclopramide HCl), PEPCID(R) (famotidine) for Oral Suspension, Oral Suspension DIURIL(R) (Chlorothiazide), AZASAN(R) Azathioprine Tablets, USP, 75/100 mg, ANUSOL-HC(R) 2.5% (Hydrocortisone Cream, USP), ANUSOL-HC(R) 25 mg Suppository (Hydrocortisone Acetate), PROCTOCORT(R) Cream (Hydrocortisone Cream, USP) 1% and PROCTOCORT(R) Suppository (Hydrocortisone Acetate Rectal Suppositories) 30 mg. Crofelemer, budesonide foam and rifaximin for additional indications are under development.
For full prescribing information and important safety information on Salix products, including BOXED WARNINGS for VISICOL, OSMOPREP and METOZOLV ODT, please visit www.salix.com where the Company promptly posts press releases, SEC filings and other important information, or contact the Company at 919-862-1000.
For more information, please visit our Website at http://www.salix.com/ or contact the Company at 919-862-1000. Information on our Website is not incorporated into our SEC filings.
Please Note: The materials provided herein contain projections and other forward-looking statements regarding future events. Such statements are just predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include, among others: the unpredictable nature of the duration and results of regulatory review of new drug applications; market acceptance for approved products; generic and other competition; the possible impairment of, or inability to obtain, intellectual property rights and the costs of obtaining such rights from third parties; our need to return to profitability; and the need to acquire new products. The reader is referred to the documents that the Company files from time to time with the Securities and Exchange Commission.
SOURCE: Salix Pharmaceuticals, Inc.
Sonoco
Adam C. Derbyshire, Executive Vice President and Chief Financial Officer or
G. Michael Freeman, Associate Vice President, Investor Relations and
Corporate Communications, 919-862-1000
Source
BOSTON, Oct 30, 2010 (BUSINESS WIRE) -- Salix Pharmaceuticals, Inc. /quotes/comstock/15*!slxp/quotes/nls/slxp (SLXP 37.83, +0.41, +1.10%) today announced that the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010) will be an important venue for ongoing discussion of hepatic encephalopathy, or HE. Numerous posters and oral presentations provide insight regarding HE's burden on patients, caregivers and the healthcare system; the earlier identification and diagnosis of HE; the growing recognition of the importance of aggressive management of HE; and the use of XIFAXAN(R) (rifaximin) 550 mg for the reduction in risk of overt HE recurrence.
"In the last decade, HE-related hospitalizations have more than doubled. Today, an estimated one third to one half of all hospitalizations in cirrhotic patients are partially or wholly attributable to hepatic encephalopathy," stated Bill Forbes, Executive Vice President, Research and Development and Chief Development Officer, Salix, "Hepatic encephalopathy signifies a poor prognosis with one-year and three-year mortality rates of 58 percent and 77 percent, respectively, after presentation of the first episode of acute HE. The introduction of XIFAXAN 550 mg, the first new therapy approved for HE in 30 years, is providing physicians a much-needed therapy to manage their patients and to help patients break the cycle of relapse. Additionally, the availability of this tolerable and efficacious treatment for overt HE has re-energized the HE research community and challenged physicians to more aggressively approach HE therapy with the intention of improving treatment success and long-term outcomes."
Rifaximin-Related Presentations at AASLD
Oral Presentation #24: Leise et al. "Impact of Rifaximin Treatment on Survival in Patients with End-stage Liver Disease." Sunday, Oct. 31, 2010, 1:00 - 2:30 p.m., Hynes, Room 312
This analysis compared the long term effect of rifaximin by comparing survival in HE patients receiving rifaximin (long-term open label trial) versus patients awaiting liver transplantation (Organ Procurement and Transplant network).
Oral Presentation #19: Vlachogiannakos et al. "Long-term Administration of Rifaximin Improves the Prognosis of Patients with Alcohol-related Decompensated Cirrhosis: A Case-control study." Sunday, Oct. 31, 2010, 1:00 - 2:30 pm, Hynes, Room 312
This study evaluated the effect of intestinal decontamination with rifaximin (1200 mg for 4 weeks) on the long-term prognosis of 23 patients with alcohol-related decompensated cirrhosis and ascites. Five-year cumulative probability of survival data were obtained.
Oral Presentation #22: Bajaj et al. "Rifaximin Improves Driving Simulator Performance in Minimal Hepatic Encephalopathy: A Double-blind, Placebo-controlled, Prospective Randomized Trial." Sunday, Oct. 31, 2010, 1:00 - 2:30 p.m., Hynes, Room 312
A total of 42 MHE patients, diagnosed using a battery of five tests of cognitive function (CB) and without overt HE, participated in the eight-week trial. Patients initially underwent a baseline evaluation of driving and navigation simulation (outcomes were speeding tickets, collisions and illegal turns), Quality of Life with Sickness Impact Profile (SIP, which includes physical/psycho-social scores), ammonia and model for end-stage liver disease (MELD) score, in addition to the CB. Patients were randomized to receive XIFAXAN 550 mg or placebo twice-daily (BID) (n=21 in each group). All evaluations were repeated at the eight-week visit. The primary outcomes were proportion improved in speeding, illegal turns and collisions; secondary outcomes were proportion improved in mean CB Zscores and SIP scores. In addition to being presented at AASLD, this study was recently published in Gastroenterology.
Poster #1192: Krag et. al. "Systematic Review and Meta-analyses of Randomised Trials on Ammonia lowering Regimens for Hepatic Encephalopathy." Monday, Nov. 1, 2010, 8:00 a.m. - 5:30 p.m., Hynes, Exhibit Hall C.
These meta-analyses of 21 randomized trials evaluated the effects of ammonia lowering interventions in the management of hepatic encephalopathy.
About Hepatic Encephalopathy
Hepatic encephalopathy (HE) is a disorder caused by chronic liver failure resulting in cognitive, psychiatric and motor impairments.The condition encompasses a wide spectrum of often reversible neuropsychiatric abnormalities caused by the inability of the liver to remove toxic products in the gut from most notably ammonia-producing bacteria. When toxins reach the central nervous system, this condition can result in symptoms ranging in severity from mild cerebral function deficits to coma. The disorder is characterized by disruption in sleep patterns, changes in personality and intellectual capacity, high blood ammonia levels, altered neuromuscular activity and electroencephalogram (EEG) abnormalities.
About XIFAXAN(R) (rifaximin) 550 mg tablets
Important Safety Information
XIFAXAN 550 mg is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients greater-than or equal to 18 years of age. In the trials of XIFAXAN for HE, 91 percent of the patients were using lactulose concomitantly. XIFAXAN has not been studied in patients with MELD scores greater than 25, and only 8.6 percent of patients in the controlled trial had MELD scores over 19. There is increased systemic exposure in patients with more severe hepatic dysfunction. Therefore, caution should be exercised when administering XIFAXAN to patients with severe hepatic impairment (Child-Pugh C).
XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, any of the rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema and anaphylaxis.
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon which may lead to overgrowth of C. difficile. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
The most common adverse reactions occurring in greater than eight percent of patients in the clinical study were edema peripheral (15 percent), nausea (14 percent), dizziness (13 percent), fatigue (12 percent), ascites (11 percent), muscle spasms (nine percent), pruritus (nine percent) and abdominal pain (nine percent).
About XIFAXAN(R) (rifaximin) 200 mg tablets
Rifaximin is a gut-selective antibiotic with negligible systemic absorption and broad-spectrum activity in vitro against both Gram-positive and Gram-negative pathogens. Rifaximin has a similar tolerability profile to that of placebo.
Rifaximin tablets 200 mg, which Salix markets in the U.S. under the trade name XIFAXAN(R) (rifaximin) tablets 200 mg, currently is approved for the treatment of patients, 12 years of age or older, with travelers' diarrhea (TD) caused by non--invasive strains of Escherichia coli. XIFAXAN should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli. XIFAXAN should be discontinued if diarrhea symptoms get worse or persist more than 24--48 hours, and alternative antibiotic therapy should be considered. In clinical trials, XIFAXAN was generally well-tolerated. The most common side effects (versus placebo) were flatulence 11.3 percent (versus 19.7 percent), headache 9.7 percent (versus 9.2 percent), abdominal pain 7.2 percent (versus 10.1 percent) and rectal tenesmus 7.2 percent (versus 8.8 percent).
Rifaximin has been used in Italy for 24 years and is approved in 33 countries. Salix acquired rights to market rifaximin in North America from Alfa Wassermann S.p.A. in Bologna, Italy. Alfa Wassermann markets rifaximin in Italy under the trade name Normix(R).
About Salix Pharmaceuticals
Salix Pharmaceuticals, Ltd., headquartered in Raleigh, NC, develops and markets prescription pharmaceutical products for the treatment of gastrointestinal diseases. Salix's strategy is to in-license late-stage or marketed proprietary therapeutic drugs, complete with any required development and regulatory submission of these products, and market them through the Company's gastroenterology specialty sales and marketing team.
Salix also markets MOVIPREP(R) (PEG 3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution), OSMOPREP(R) (sodium phosphate monobasic monohydrate, USP and sodium phosphate dibasic anhydrous, USP) Tablets, VISICOL(R) (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets, APRISO(TM) (mesalamine) extended-release capsules 0.375 g., METOZOLV(R) ODT (metoclopramide HCl), PEPCID(R) (famotidine) for Oral Suspension, Oral Suspension DIURIL(R) (Chlorothiazide), AZASAN(R) Azathioprine Tablets, USP, 75/100 mg, ANUSOL-HC(R) 2.5% (Hydrocortisone Cream, USP), ANUSOL-HC(R) 25 mg Suppository (Hydrocortisone Acetate), PROCTOCORT(R) Cream (Hydrocortisone Cream, USP) 1% and PROCTOCORT(R) Suppository (Hydrocortisone Acetate Rectal Suppositories) 30 mg. Crofelemer, budesonide foam and rifaximin for additional indications are under development.
For full prescribing information and important safety information on Salix products, including BOXED WARNINGS for VISICOL, OSMOPREP and METOZOLV ODT, please visit www.salix.com where the Company promptly posts press releases, SEC filings and other important information, or contact the Company at 919-862-1000.
For more information, please visit our Website at http://www.salix.com/ or contact the Company at 919-862-1000. Information on our Website is not incorporated into our SEC filings.
Please Note: The materials provided herein contain projections and other forward-looking statements regarding future events. Such statements are just predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include, among others: the unpredictable nature of the duration and results of regulatory review of new drug applications; market acceptance for approved products; generic and other competition; the possible impairment of, or inability to obtain, intellectual property rights and the costs of obtaining such rights from third parties; our need to return to profitability; and the need to acquire new products. The reader is referred to the documents that the Company files from time to time with the Securities and Exchange Commission.
SOURCE: Salix Pharmaceuticals, Inc.
Sonoco
Adam C. Derbyshire, Executive Vice President and Chief Financial Officer or
G. Michael Freeman, Associate Vice President, Investor Relations and
Corporate Communications, 919-862-1000
Source
Race Affects Hepatitis C Recurrence After Liver Transplant: Study
Patients who receive organ from a white donor at higher risk, researchers find
Posted: October 30, 2010
SATURDAY, Oct. 30 (HealthDay News) -- Hepatitis C patients who receive a liver from a white donor have significantly more aggressive recurrent hepatitis than those who receive a liver from a black donor, researchers have found.
This is especially true for black patients who receive a liver from a white donor, the study authors noted.
Researchers from Henry Ford Hospital in Detroit looked at 165 hepatitis C patients who received a liver transplant at the hospital between 2000 and 2006. The patients were given a recurrent hepatitis C virus (HCV) score between 1 and 3.
The average recurrent HCV score for patients for each donor/recipient race combination was:
• White donor/white recipient: 1.54
• White donor/black recipient: 1.89
• Black donor/white recipient: 1.18
• Black donor/black recipient: 1.23
"The data suggests a graft from a white donor is potentially one more important variable in identifying patients at risk for more aggressive recurrent hepatitis after transplant and warrants further study," lead author Dr. Matthew Moeller, a gastroenterology fellow, said in a hospital news release.
The study findings were slated to be presented Oct. 29 at the annual meeting of the American Association for the Study of Liver Diseases, in Boston.
According to data from the United Network for Organ Sharing cited in the news release, there are almost 18,000 Americans on the waiting list for liver transplants.
More information
The American Academy of Family Physicians has more about hepatitis C
Source
Posted: October 30, 2010
SATURDAY, Oct. 30 (HealthDay News) -- Hepatitis C patients who receive a liver from a white donor have significantly more aggressive recurrent hepatitis than those who receive a liver from a black donor, researchers have found.
This is especially true for black patients who receive a liver from a white donor, the study authors noted.
Researchers from Henry Ford Hospital in Detroit looked at 165 hepatitis C patients who received a liver transplant at the hospital between 2000 and 2006. The patients were given a recurrent hepatitis C virus (HCV) score between 1 and 3.
The average recurrent HCV score for patients for each donor/recipient race combination was:
• White donor/white recipient: 1.54
• White donor/black recipient: 1.89
• Black donor/white recipient: 1.18
• Black donor/black recipient: 1.23
"The data suggests a graft from a white donor is potentially one more important variable in identifying patients at risk for more aggressive recurrent hepatitis after transplant and warrants further study," lead author Dr. Matthew Moeller, a gastroenterology fellow, said in a hospital news release.
The study findings were slated to be presented Oct. 29 at the annual meeting of the American Association for the Study of Liver Diseases, in Boston.
According to data from the United Network for Organ Sharing cited in the news release, there are almost 18,000 Americans on the waiting list for liver transplants.
More information
The American Academy of Family Physicians has more about hepatitis C
Source
Wake Forest scientists successfully grow 'miniature livers'
Updated Oct. 30, 2010 at 11:29 a.m.
By Local Tech Wire
WINSTON-SALEM, N.C. – Scientists at Wake Forest University have engineered what they call a “miniature” liver in a lab that functions like the human organ.
It’s the latest tissue breakthrough at the Institute for Regenerative Medicine, which in 2006 reported the growth and transplant of bladders into humans. Anthony Atala, MD, the director of the institute, is a leading pioneer in the field of regenerative science.
Researchers are reporting their findings Sunday at the American Association for the Study of Liver Diseases as well as in the journal Hepatology.
These miniature livers function “at least in a laboratory setting,” the university said. Researchers plan now to study whether the livers will work after being transplanted in an animal model.
The livers were grown from human liver cells and are 1 inch in diameter and weigh some 20 ounces, the university said. In order to perform successfully in humans, an engineered liver would have to weigh at least 1 pound, the scientists said.
The achievement could lead to breakthroughs in treatments of people with liver disease and other ailments.
“We are excited about the possibilities this research represents, but must stress that we’re at an early stage and many technical hurdles must be overcome before it could benefit patients,” said Shay Soker, a professor of regenerative medicine who is the project director, in a statement. “Not only must we learn how to grow billions of liver cells at one time in order to engineer livers large enough for patients, but we must determine whether these organs are safe to use in patients.”
The miniature livers were produced after animal livers were treated to remove all its cells in a process called decellularization that left what scientists called a “skeleton” support structure. Immature human liver cells and cells that line blood vessels were then added to the structure to the network of blood vessels left in the animal livers.
The skeleton and cells were then placed into a so-called bioreactor that provided nutrients and oxygen.
Institute researchers are working on 22 different kinds of cells and organs
Source
By Local Tech Wire
WINSTON-SALEM, N.C. – Scientists at Wake Forest University have engineered what they call a “miniature” liver in a lab that functions like the human organ.
It’s the latest tissue breakthrough at the Institute for Regenerative Medicine, which in 2006 reported the growth and transplant of bladders into humans. Anthony Atala, MD, the director of the institute, is a leading pioneer in the field of regenerative science.
Researchers are reporting their findings Sunday at the American Association for the Study of Liver Diseases as well as in the journal Hepatology.
These miniature livers function “at least in a laboratory setting,” the university said. Researchers plan now to study whether the livers will work after being transplanted in an animal model.
The livers were grown from human liver cells and are 1 inch in diameter and weigh some 20 ounces, the university said. In order to perform successfully in humans, an engineered liver would have to weigh at least 1 pound, the scientists said.
The achievement could lead to breakthroughs in treatments of people with liver disease and other ailments.
“We are excited about the possibilities this research represents, but must stress that we’re at an early stage and many technical hurdles must be overcome before it could benefit patients,” said Shay Soker, a professor of regenerative medicine who is the project director, in a statement. “Not only must we learn how to grow billions of liver cells at one time in order to engineer livers large enough for patients, but we must determine whether these organs are safe to use in patients.”
The miniature livers were produced after animal livers were treated to remove all its cells in a process called decellularization that left what scientists called a “skeleton” support structure. Immature human liver cells and cells that line blood vessels were then added to the structure to the network of blood vessels left in the animal livers.
The skeleton and cells were then placed into a so-called bioreactor that provided nutrients and oxygen.
Institute researchers are working on 22 different kinds of cells and organs
Source
Idera Pharmaceuticals Presents Phase 1 Data on IMO-2125 Demonstrating Induction of Broad Antiviral Immune Response in Null-Responder HCV Patients
CAMBRIDGE, Mass., Oct 30, 2010 (BUSINESS WIRE) -- Idera Pharmaceuticals, Inc. /quotes/comstock/15*!idra/quotes/nls/idra (IDRA 2.76, -0.03, -1.08%) announced today the presentation of data from a Phase 1 clinical trial evaluating IMO-2125, a novel immune modulator, in null-responder patients with chronic hepatitis C virus (HCV) infection. The oral presentation, entitled "IMO-2125, a TLR9 Agonist, Induces Immune Responses which Correlate with Reductions in Viral Load in Null-Responder HCV Patients" (Abstract #33), is being made by Maribel Rodriguez-Torres, M.D., of Fundacion de Investigacion in Santurce, Puerto Rico at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
"Null-responder patients are the most difficult HCV patients to treat and represent an area of significant need as there are currently no approved treatment options for these patients," said Dr. Rodriguez-Torres. "The data presented show that IMO-2125 induced a broad immune response including induction of endogenous interferons. This suggests that IMO-2125 may provide an alternative to the recombinant interferon component of HCV treatment."
This Phase 1 clinical trial evaluated 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy at five dose levels and 10 patients received placebo once per week for four weeks. Most of these patients were infected with HCV genotype 1 and had the CT or TT IL28B gene alleles. IMO-2125 was well tolerated at all dose levels. IMO-2125 induced a broad immune response with dose-dependent increases in serum concentrations of antiviral proteins and activation of cellular immune responses. Across the three highest dose levels, seventy-five percent of patients achieved a 1 log10 or greater decrease in viral load at least once during the treatment period. Consistent with the proposed mechanism of IMO-2125, induction of higher serum concentrations of interferon-alpha correlated with greater decreases in HCV viral load. Additional patients are being enrolled in this Phase 1 trial to evaluate twice-weekly dosing of IMO-2125.
"These data demonstrate that in the trial once-weekly dosing of IMO-2125 in null-responders induced a distinctive pattern of immune activation and achieved dose-dependent viral load reductions," said Robert Arbeit, M.D., VP of Clinical Development of Idera Pharmaceuticals. "To optimize the dosing schedule and maximize antiviral activity we are continuing the trial to evaluate twice-weekly dosing of IMO-2125."
Dr. Arbeit continued, "In addition, we are conducting a Phase 1 trial in treatment-naive HCV patients evaluating IMO-2125 at multiple dose levels using both once-weekly and twice-weekly dosing regimens for four weeks in combination with ribavirin, compared to a control arm of patients receiving pegylated recombinant interferon-alpha and ribavirin. We expect to report top-line data from this trial in the fourth quarter."
"The data presented from this trial support the target product profile of IMO-2125 as a novel immune modulator with the potential to be used as a key component of HCV treatment," said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer at Idera. "Prior to initiating a Phase 2 clinical trial for IMO-2125, we plan to analyze the full data sets from the ongoing Phase 1 IMO-2125 trials and evaluate the upcoming changes in the development and treatment landscape for HCV. We expect that, after assessing these factors, we will outline our clinical development strategy and plans for a Phase 2 program for IMO-2125 by the end of 2010."
Phase 1 Clinical Trial in Null-Responder HCV Patients
Study Design:
IMO-2125 was administered subcutaneously once per week for four weeks at five dose levels of 0.04, 0.08, 0.16, 0.32 and 0.48 mg/kg. The clinical trial was designed to evaluate safety, immunological activity and reduction in HCV viral load. Eight patients were enrolled at each dose level with an additional two patients randomized to receive placebo treatment for a total of 10 per cohort. All patients enrolled in the trial were null-responders, defined as patients who failed to achieve a 2 log10 reduction in viral load with 12 to 24 weeks of previous treatment with pegylated recombinant interferon-alpha plus ribavirin.
Study Results:
Patient Population
This Phase 1 clinical trial evaluated 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy and 10 patients received placebo. Patients were predominantly infected with HCV genotype 1 (98%) and over 90% were IL-28B genotypes CT or TT. At enrollment, the patients had high viral load (mean HCV RNA, 6.8 log10) and elevated levels of IP-10 (mean, 561 pg/mL). These factors are generally associated with poor response to standard of care treatment.
Safety
IMO-2125 was well tolerated for four weeks of treatment. There were no treatment-related serious adverse events (SAEs) and no treatment-related discontinuations. The most common adverse events were "flu-like symptoms" that typically lasted less than 1 day, injection site reactions and headache. There were no clinically significant adverse effects on safety laboratory parameters.
IMO-2125 Activation of Immune Response
Patients receiving IMO-2125 showed dose-dependent increases in serum concentrations of endogenous interferon-alpha, which were more pronounced after the fourth dose compared to the first dose. Patients receiving IMO-2125 showed dose-dependent increases in serum concentrations of IP-10 and 2', 5'-oligoadenylate synthetase (2', 5'-OAS), host proteins which are known to contribute to antiviral activity. Patients receiving IMO-2125 showed dose-dependent increases in cell markers of immune activation, including increases in NK cells, helper T cells and cytotoxic T cells.
HCV RNA reduction
Patients receiving IMO-2125 showed dose-dependent reduction in HCV RNA viral load. At dose levels of 0.32 and 0.48 mg/kg/week, six of eight patients and seven of eight patients, respectively, achieved a reduction in viral load of 1 log10 or more at least once during the treatment period; in both groups the median for the maximum viral load reductions was 1.6 log10. IL28B genotype data are available for 14 of the 16 patients treated with IMO-2125 at 0.32 or 0.48 mg/kg/week. Thirteen of these patients had CT or TT IL28B genotype, of which 10 had maximum viral load reductions ranging from -1 to -2.6 log10 at least once during the treatment period. The 14th patient had CC IL28B genotype and had a maximum viral load reduction of 2.5 log10 at least once during the treatment period. Serum concentrations of endogenous interferon-alpha induced by IMO-2125 treatment correlated with reductions in HCV RNA viral levels.
Authors of the presentation and study investigators include: Maribel Rodriguez-Torres, M.D., of Fundacion de Investigation, Santurce PR; Reem Ghalib, M.D., of The Liver Institute, Dallas TX; Stuart Gordon, M.D., of Henry Ford Medical Center, Novi, MI; Eric Lawitz, M.D., of Alamo Medical Research, San Antonio TX; Keyur Patel, M.D., of Duke University Medical Center, Durham NC; Ronald Pruitt, M.D., of Nashville Gastrointestinal Specialists, Nashville, TN; Aasim Sheikh, M.D., of Gastrointestinal Specialists of Georgia, Marietta GA; Andrew Muir, M.D., MHS, of Duke Clinical Research Institute, Durham, NC; John McHutchison, M.D., formerly of Duke Clinical Research Institute, Durham, NC; and Alice Bexon, MBChB, Ekambar Kandimalla, Ph.D., Melissa Precopio, Ph.D. and Tim Sullivan, Ph.D., of Idera Pharmaceuticals, Inc.
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 is currently 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. IMO-2125 is also being evaluated in a Phase 1 clinical trial in treatment-naive HCV patients in combination with ribavirin for 4 weeks.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals develops drug candidates to treat infectious diseases, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. Our proprietary drug candidates are designed to modulate specific Toll-like Receptors (TLRs), which are a family of immune system receptors that direct immune system responses. Our pioneering DNA and RNA chemistry expertise enables us to create drug candidates for our internal development programs and our partnered programs, and generates opportunities for additional 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 studies and early clinical trials such as the trials 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 June 30, 2010, which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.
SOURCE: Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
cerdman@macbiocom.com
Source
"Null-responder patients are the most difficult HCV patients to treat and represent an area of significant need as there are currently no approved treatment options for these patients," said Dr. Rodriguez-Torres. "The data presented show that IMO-2125 induced a broad immune response including induction of endogenous interferons. This suggests that IMO-2125 may provide an alternative to the recombinant interferon component of HCV treatment."
This Phase 1 clinical trial evaluated 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy at five dose levels and 10 patients received placebo once per week for four weeks. Most of these patients were infected with HCV genotype 1 and had the CT or TT IL28B gene alleles. IMO-2125 was well tolerated at all dose levels. IMO-2125 induced a broad immune response with dose-dependent increases in serum concentrations of antiviral proteins and activation of cellular immune responses. Across the three highest dose levels, seventy-five percent of patients achieved a 1 log10 or greater decrease in viral load at least once during the treatment period. Consistent with the proposed mechanism of IMO-2125, induction of higher serum concentrations of interferon-alpha correlated with greater decreases in HCV viral load. Additional patients are being enrolled in this Phase 1 trial to evaluate twice-weekly dosing of IMO-2125.
"These data demonstrate that in the trial once-weekly dosing of IMO-2125 in null-responders induced a distinctive pattern of immune activation and achieved dose-dependent viral load reductions," said Robert Arbeit, M.D., VP of Clinical Development of Idera Pharmaceuticals. "To optimize the dosing schedule and maximize antiviral activity we are continuing the trial to evaluate twice-weekly dosing of IMO-2125."
Dr. Arbeit continued, "In addition, we are conducting a Phase 1 trial in treatment-naive HCV patients evaluating IMO-2125 at multiple dose levels using both once-weekly and twice-weekly dosing regimens for four weeks in combination with ribavirin, compared to a control arm of patients receiving pegylated recombinant interferon-alpha and ribavirin. We expect to report top-line data from this trial in the fourth quarter."
"The data presented from this trial support the target product profile of IMO-2125 as a novel immune modulator with the potential to be used as a key component of HCV treatment," said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer at Idera. "Prior to initiating a Phase 2 clinical trial for IMO-2125, we plan to analyze the full data sets from the ongoing Phase 1 IMO-2125 trials and evaluate the upcoming changes in the development and treatment landscape for HCV. We expect that, after assessing these factors, we will outline our clinical development strategy and plans for a Phase 2 program for IMO-2125 by the end of 2010."
Phase 1 Clinical Trial in Null-Responder HCV Patients
Study Design:
IMO-2125 was administered subcutaneously once per week for four weeks at five dose levels of 0.04, 0.08, 0.16, 0.32 and 0.48 mg/kg. The clinical trial was designed to evaluate safety, immunological activity and reduction in HCV viral load. Eight patients were enrolled at each dose level with an additional two patients randomized to receive placebo treatment for a total of 10 per cohort. All patients enrolled in the trial were null-responders, defined as patients who failed to achieve a 2 log10 reduction in viral load with 12 to 24 weeks of previous treatment with pegylated recombinant interferon-alpha plus ribavirin.
Study Results:
Patient Population
This Phase 1 clinical trial evaluated 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy and 10 patients received placebo. Patients were predominantly infected with HCV genotype 1 (98%) and over 90% were IL-28B genotypes CT or TT. At enrollment, the patients had high viral load (mean HCV RNA, 6.8 log10) and elevated levels of IP-10 (mean, 561 pg/mL). These factors are generally associated with poor response to standard of care treatment.
Safety
IMO-2125 was well tolerated for four weeks of treatment. There were no treatment-related serious adverse events (SAEs) and no treatment-related discontinuations. The most common adverse events were "flu-like symptoms" that typically lasted less than 1 day, injection site reactions and headache. There were no clinically significant adverse effects on safety laboratory parameters.
IMO-2125 Activation of Immune Response
Patients receiving IMO-2125 showed dose-dependent increases in serum concentrations of endogenous interferon-alpha, which were more pronounced after the fourth dose compared to the first dose. Patients receiving IMO-2125 showed dose-dependent increases in serum concentrations of IP-10 and 2', 5'-oligoadenylate synthetase (2', 5'-OAS), host proteins which are known to contribute to antiviral activity. Patients receiving IMO-2125 showed dose-dependent increases in cell markers of immune activation, including increases in NK cells, helper T cells and cytotoxic T cells.
HCV RNA reduction
Patients receiving IMO-2125 showed dose-dependent reduction in HCV RNA viral load. At dose levels of 0.32 and 0.48 mg/kg/week, six of eight patients and seven of eight patients, respectively, achieved a reduction in viral load of 1 log10 or more at least once during the treatment period; in both groups the median for the maximum viral load reductions was 1.6 log10. IL28B genotype data are available for 14 of the 16 patients treated with IMO-2125 at 0.32 or 0.48 mg/kg/week. Thirteen of these patients had CT or TT IL28B genotype, of which 10 had maximum viral load reductions ranging from -1 to -2.6 log10 at least once during the treatment period. The 14th patient had CC IL28B genotype and had a maximum viral load reduction of 2.5 log10 at least once during the treatment period. Serum concentrations of endogenous interferon-alpha induced by IMO-2125 treatment correlated with reductions in HCV RNA viral levels.
Authors of the presentation and study investigators include: Maribel Rodriguez-Torres, M.D., of Fundacion de Investigation, Santurce PR; Reem Ghalib, M.D., of The Liver Institute, Dallas TX; Stuart Gordon, M.D., of Henry Ford Medical Center, Novi, MI; Eric Lawitz, M.D., of Alamo Medical Research, San Antonio TX; Keyur Patel, M.D., of Duke University Medical Center, Durham NC; Ronald Pruitt, M.D., of Nashville Gastrointestinal Specialists, Nashville, TN; Aasim Sheikh, M.D., of Gastrointestinal Specialists of Georgia, Marietta GA; Andrew Muir, M.D., MHS, of Duke Clinical Research Institute, Durham, NC; John McHutchison, M.D., formerly of Duke Clinical Research Institute, Durham, NC; and Alice Bexon, MBChB, Ekambar Kandimalla, Ph.D., Melissa Precopio, Ph.D. and Tim Sullivan, Ph.D., of Idera Pharmaceuticals, Inc.
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 is currently 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. IMO-2125 is also being evaluated in a Phase 1 clinical trial in treatment-naive HCV patients in combination with ribavirin for 4 weeks.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals develops drug candidates to treat infectious diseases, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. Our proprietary drug candidates are designed to modulate specific Toll-like Receptors (TLRs), which are a family of immune system receptors that direct immune system responses. Our pioneering DNA and RNA chemistry expertise enables us to create drug candidates for our internal development programs and our partnered programs, and generates opportunities for additional 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 studies and early clinical trials such as the trials 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 June 30, 2010, which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.
SOURCE: Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
cerdman@macbiocom.com
Source
Vertex, Merck Drugs Help More With Faster Cure for Hepatitis C
October 30, 2010, 9:36 AM EDT
By Michelle Fay Cortez
Oct. 30 (Bloomberg) -- Vertex Pharmaceuticals Inc. and Merck & Co. said their experimental drugs for hepatitis C cured more patients than traditional treatment, and many people were able to take a shorter, less toxic course of therapy.
Two-thirds of patients given Vertex’s telaprevir were able to cut their treatment time in half to six months, and about 90 percent were cured, two studies funded by the Cambridge, Massachusetts-based company found. Nearly half of those given boceprevir in studies from Whitehouse Station, New Jersey-based Merck were able to reduce their treatment times to six months to nine months, with similar high rates of cure.
The findings presented today at the American Association for the Study of Liver Disease meeting in Boston will help usher in a new era of treatment for hepatitis C, doctors say. The chronic condition affects nearly 4 million Americans and 200 million people worldwide, according to the National Institutes of Health. The companies plan to file for U.S. regulatory approval of the drugs by the end of the year.
“The current standard of care is long and it’s not easy to take,” said Michael Charlton, director of the Mayo Clinic’s liver transplant program in Rochester, Minnesota. “The appeal of the new drugs is the shorter treatment, and you get there quicker with telaprevir,” he said in a telephone interview.
Standard Treatment
Hepatitis C often persists as a chronic condition that causes nausea, weakness and exhaustion as it destroys the liver over time. Interferon, the standard of care when paired with the generic drug ribavirin to increase potency, works by boosting the immune system. The yearlong treatment causes aches and pains similar to the flu that may last the entire year of treatment and cures about half of those who can tolerate it.
Roche Holding AG of Basel, Switzerland, sells a version of interferon under the brand name Pegasys, while Merck sells a form called PegIntron.
Telaprevir will capture about three-fourths of the demand for the new medicines, said Howard Liang, an analyst at Leerink Swann & Co. in Boston, in a telephone interview. The drug, which Vertex is developing with New Brunswick, New Jersey-based Johnson & Johnson, will generate about $2.6 billion annually by 2013, he said.
--Editors: Andrew Pollack, Donna Alvarado
To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net
Source
By Michelle Fay Cortez
Oct. 30 (Bloomberg) -- Vertex Pharmaceuticals Inc. and Merck & Co. said their experimental drugs for hepatitis C cured more patients than traditional treatment, and many people were able to take a shorter, less toxic course of therapy.
Two-thirds of patients given Vertex’s telaprevir were able to cut their treatment time in half to six months, and about 90 percent were cured, two studies funded by the Cambridge, Massachusetts-based company found. Nearly half of those given boceprevir in studies from Whitehouse Station, New Jersey-based Merck were able to reduce their treatment times to six months to nine months, with similar high rates of cure.
The findings presented today at the American Association for the Study of Liver Disease meeting in Boston will help usher in a new era of treatment for hepatitis C, doctors say. The chronic condition affects nearly 4 million Americans and 200 million people worldwide, according to the National Institutes of Health. The companies plan to file for U.S. regulatory approval of the drugs by the end of the year.
“The current standard of care is long and it’s not easy to take,” said Michael Charlton, director of the Mayo Clinic’s liver transplant program in Rochester, Minnesota. “The appeal of the new drugs is the shorter treatment, and you get there quicker with telaprevir,” he said in a telephone interview.
Standard Treatment
Hepatitis C often persists as a chronic condition that causes nausea, weakness and exhaustion as it destroys the liver over time. Interferon, the standard of care when paired with the generic drug ribavirin to increase potency, works by boosting the immune system. The yearlong treatment causes aches and pains similar to the flu that may last the entire year of treatment and cures about half of those who can tolerate it.
Roche Holding AG of Basel, Switzerland, sells a version of interferon under the brand name Pegasys, while Merck sells a form called PegIntron.
Telaprevir will capture about three-fourths of the demand for the new medicines, said Howard Liang, an analyst at Leerink Swann & Co. in Boston, in a telephone interview. The drug, which Vertex is developing with New Brunswick, New Jersey-based Johnson & Johnson, will generate about $2.6 billion annually by 2013, he said.
--Editors: Andrew Pollack, Donna Alvarado
To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net
Source
ANA598 Data Presented at AASLD Highlight Positive Clinical Profile of DAA Entering Phase IIb
Oral Presentation at 3:00 pm on October 31 at AASLD
SAN DIEGO, Oct. 30 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced the ANA598 data to be presented at the 61st Annual Meeting of the American Association for the Study of Liver Disease (AASLD) in Boston, MA. ANA598, the Company's direct-acting antiviral (DAA) being developed for the treatment of hepatitis C, will be discussed in two presentations at the conference:
• On Sunday, October 31, 2010 at 3:00 pm Eastern Daylight Time, Eric Lawitz, M.D., a principal investigator of the study, will give an oral presentation titled, "Safety and Antiviral Activity of ANA598 in Combination with Pegylated Interferon alpha 2A Plus Ribavirin in Treatment-Naive Genotype-1 Chronic HCV Patients." The slides will be available on the Company's website at www.anadyspharma.com following conclusion of the presentation.
• On Tuesday, November 2, 2010 at 7:00 am Eastern Daylight Time, Anadys will present data in a poster titled, "IL28B Polymorphism and Kinetics of Antiviral Activity for ANA598 in Combination with Pegylated Interferon alpha 2A Plus Ribavirin in Treatment-Naive Genotype-1 Chronic HCV Patients." The poster will be available on the Company's website at www.anadyspharma.com.
"We are pleased with the positive clinical profile seen to date for ANA598, as well as its preclinical properties that support investigation of combinations with other direct antivirals," said James L. Freddo, M.D., Senior Vice President, Drug Development and Chief Medical Officer of Anadys. "In the upcoming Phase IIb study, we look forward to testing ANA598 for the first time in treatment-experienced patients, as well as in a larger population of treatment-naive patients."
In the oral presentation, data from an ongoing Phase II combination study show that ANA598 added to pegylated interferon and ribavirin (current standard of care, or SOC) accelerated the rate of patients achieving undetectable levels of virus compared to placebo plus SOC, and that the antiviral response was equivalent at 200 mg bid and 400 mg bid ANA598. The data from the study further show a durable antiviral response through 12 weeks, with only a single patient (<2% of patients in the ANA598 arms) experiencing viral breakthrough while receiving ANA598 plus SOC. The safety profile of ANA598 through 12 weeks was excellent in the study, with reported adverse events being typical for patients treated with interferon and ribavirin alone, and the incidence of rash in patients receiving ANA598 200 mg bid plus SOC in the study was comparable to the group receiving placebo plus SOC.
Additional data from the Phase II combination study will be presented reflecting the persistence of ANA598's benefit beyond week 12. 39 of 41 patients (>95%) who achieved undetectable levels of virus at week 12 in the two active arms have maintained undetectable levels while continuing to receive SOC through the latest available measurements. For patients who, per protocol, concluded all treatment at week 24, interim analysis of SVR data for available patients indicates that 8 of 11 patients maintained undetectable levels of virus 12 weeks later, referred to as a Sustained Virological Response 12, or SVR12. The three patients who relapsed after concluding treatment at week 24 demonstrated the lowest week 4 ribavirin levels of all patients who concluded treatment at week 24, consistent with the known impact of ribavirin levels on converting on-treatment response to SVR. Data is available for three patients 24 weeks after concluding treatment. All three patients achieved an SVR24, recognized as a viral cure.
In the poster presentation on Tuesday, November 2, 2010, Anadys will present additional data from the Phase II combination study showing that the addition of ANA598 to SOC conferred benefit independent of a patient's IL-28B genotype. In patients with the IL-28B genotype most responsive to SOC (referred to as CC), ANA598 accelerated the rate of achieving undetectable levels of virus, with 82% of patients who received ANA598 plus SOC achieving undetectable levels by week 4, compared to 27% of patients who received placebo plus SOC. In patients with IL-28B genotypes less responsive to SOC (referred to as CT and TT, or collectively non-CC), ANA598 both accelerated the rate of achieving undetectable levels of virus and increased the percentage of patients with undetectable levels of virus at week 12. In the non-CC patients, 38% of patients who received ANA598 plus SOC achieved undetectable levels of virus by week 4, compared to 8% of patients who received placebo plus SOC, and 73% of patients who received ANA598 plus SOC achieved undetectable levels of virus at week 12, compared to 47% of patients who received placebo plus SOC.
Phase II Combination Study
In the ongoing Phase II study, approximately 90 treatment-naive genotype 1 HCV patients have received ANA598 or placebo in combination with Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin, USP) for 12 weeks at dose levels of 200 mg twice-daily (bid) or 400 mg bid, each with a loading dose of 800 mg bid on day one. After week 12, patients are to continue receiving SOC. Patients who achieved undetectable levels of virus at weeks 4 and 12 were randomized to stop all treatment at week 24 or 48. The primary endpoint of the study is the proportion of patients who achieve undetectable levels of virus at week 12 (defined as complete Early Virological Response, or cEVR). Additional endpoints include safety and tolerability as well as the proportion of patients with undetectable levels of virus at week 4 (defined as Rapid Virological Response, or RVR). Patients are being followed for 24 weeks after stopping therapy to determine the rate of Sustained Virological Response, or SVR. Approximately 90 patients have been enrolled in this study – with approximately 30 patients receiving ANA598 plus SOC at each dose level and 30 patients receiving placebo plus SOC. The study is being managed by the Duke Clinical Research Institute (DCRI) and is being conducted at a number of clinical sites in the United States.
About Anadys
Anadys Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to improving patient care by developing novel medicines for the treatment of hepatitis C. The Company believes hepatitis C represents a large unmet medical need in which meaningful improvements in treatment outcomes may be attainable with the introduction of new medicines. Anadys is preparing to initiate a Phase IIb study of ANA598, the Company's direct-acting antiviral or DAA, added to current standard of care for the treatment of hepatitis C. The Company is also preparing to resume clinical development of ANA773, the Company's oral, small-molecule inducer of endogenous interferons that acts via the Toll like receptor 7, or TLR7, pathway in hepatitis C.
Safe Harbor Statement
Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to (i) the plans and trial design for the planned ANA598 Phase IIb study; (ii) the belief that the preclinical properties of ANA598 support investigation of combinations with other direct antivirals and the ability to pursue such combinations; (iii) assessments of the potency, safety and tolerability profile of ANA598 based on the 12 week results; (iv) the durability of antiviral response after treatment with ANA598 is concluded as well as interim SVR rates based on data available to date; and (v) the beneficial effect of ANA598 in both CC and non-CC patients based on observations in the Phase II combination study. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical and early clinical studies may not be predictive of future results, and Anadys cannot provide any assurances that ANA598 or ANA773 will not have unforeseen safety issues, will have favorable results in future clinical trials or will receive regulatory approval. In addition, Anadys' results may be affected by competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to enter into transactions around its product candidates, its ability to successfully develop and market products, difficulties or delays in its preclinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-K for the year ended December 31, 2009, Form 10-Q for the quarter ended September 30, 2010 and Form 8-K filed on October 15, 2010. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
Pegasys® and Copegus® are registered trademarks of Hoffman-La Roche Inc.
SOURCE Anadys Pharmaceuticals, Inc.
RELATED LINKS
http://www.anadyspharma.com/
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SAN DIEGO, Oct. 30 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced the ANA598 data to be presented at the 61st Annual Meeting of the American Association for the Study of Liver Disease (AASLD) in Boston, MA. ANA598, the Company's direct-acting antiviral (DAA) being developed for the treatment of hepatitis C, will be discussed in two presentations at the conference:
• On Sunday, October 31, 2010 at 3:00 pm Eastern Daylight Time, Eric Lawitz, M.D., a principal investigator of the study, will give an oral presentation titled, "Safety and Antiviral Activity of ANA598 in Combination with Pegylated Interferon alpha 2A Plus Ribavirin in Treatment-Naive Genotype-1 Chronic HCV Patients." The slides will be available on the Company's website at www.anadyspharma.com following conclusion of the presentation.
• On Tuesday, November 2, 2010 at 7:00 am Eastern Daylight Time, Anadys will present data in a poster titled, "IL28B Polymorphism and Kinetics of Antiviral Activity for ANA598 in Combination with Pegylated Interferon alpha 2A Plus Ribavirin in Treatment-Naive Genotype-1 Chronic HCV Patients." The poster will be available on the Company's website at www.anadyspharma.com.
"We are pleased with the positive clinical profile seen to date for ANA598, as well as its preclinical properties that support investigation of combinations with other direct antivirals," said James L. Freddo, M.D., Senior Vice President, Drug Development and Chief Medical Officer of Anadys. "In the upcoming Phase IIb study, we look forward to testing ANA598 for the first time in treatment-experienced patients, as well as in a larger population of treatment-naive patients."
In the oral presentation, data from an ongoing Phase II combination study show that ANA598 added to pegylated interferon and ribavirin (current standard of care, or SOC) accelerated the rate of patients achieving undetectable levels of virus compared to placebo plus SOC, and that the antiviral response was equivalent at 200 mg bid and 400 mg bid ANA598. The data from the study further show a durable antiviral response through 12 weeks, with only a single patient (<2% of patients in the ANA598 arms) experiencing viral breakthrough while receiving ANA598 plus SOC. The safety profile of ANA598 through 12 weeks was excellent in the study, with reported adverse events being typical for patients treated with interferon and ribavirin alone, and the incidence of rash in patients receiving ANA598 200 mg bid plus SOC in the study was comparable to the group receiving placebo plus SOC.
Additional data from the Phase II combination study will be presented reflecting the persistence of ANA598's benefit beyond week 12. 39 of 41 patients (>95%) who achieved undetectable levels of virus at week 12 in the two active arms have maintained undetectable levels while continuing to receive SOC through the latest available measurements. For patients who, per protocol, concluded all treatment at week 24, interim analysis of SVR data for available patients indicates that 8 of 11 patients maintained undetectable levels of virus 12 weeks later, referred to as a Sustained Virological Response 12, or SVR12. The three patients who relapsed after concluding treatment at week 24 demonstrated the lowest week 4 ribavirin levels of all patients who concluded treatment at week 24, consistent with the known impact of ribavirin levels on converting on-treatment response to SVR. Data is available for three patients 24 weeks after concluding treatment. All three patients achieved an SVR24, recognized as a viral cure.
In the poster presentation on Tuesday, November 2, 2010, Anadys will present additional data from the Phase II combination study showing that the addition of ANA598 to SOC conferred benefit independent of a patient's IL-28B genotype. In patients with the IL-28B genotype most responsive to SOC (referred to as CC), ANA598 accelerated the rate of achieving undetectable levels of virus, with 82% of patients who received ANA598 plus SOC achieving undetectable levels by week 4, compared to 27% of patients who received placebo plus SOC. In patients with IL-28B genotypes less responsive to SOC (referred to as CT and TT, or collectively non-CC), ANA598 both accelerated the rate of achieving undetectable levels of virus and increased the percentage of patients with undetectable levels of virus at week 12. In the non-CC patients, 38% of patients who received ANA598 plus SOC achieved undetectable levels of virus by week 4, compared to 8% of patients who received placebo plus SOC, and 73% of patients who received ANA598 plus SOC achieved undetectable levels of virus at week 12, compared to 47% of patients who received placebo plus SOC.
Phase II Combination Study
In the ongoing Phase II study, approximately 90 treatment-naive genotype 1 HCV patients have received ANA598 or placebo in combination with Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin, USP) for 12 weeks at dose levels of 200 mg twice-daily (bid) or 400 mg bid, each with a loading dose of 800 mg bid on day one. After week 12, patients are to continue receiving SOC. Patients who achieved undetectable levels of virus at weeks 4 and 12 were randomized to stop all treatment at week 24 or 48. The primary endpoint of the study is the proportion of patients who achieve undetectable levels of virus at week 12 (defined as complete Early Virological Response, or cEVR). Additional endpoints include safety and tolerability as well as the proportion of patients with undetectable levels of virus at week 4 (defined as Rapid Virological Response, or RVR). Patients are being followed for 24 weeks after stopping therapy to determine the rate of Sustained Virological Response, or SVR. Approximately 90 patients have been enrolled in this study – with approximately 30 patients receiving ANA598 plus SOC at each dose level and 30 patients receiving placebo plus SOC. The study is being managed by the Duke Clinical Research Institute (DCRI) and is being conducted at a number of clinical sites in the United States.
About Anadys
Anadys Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to improving patient care by developing novel medicines for the treatment of hepatitis C. The Company believes hepatitis C represents a large unmet medical need in which meaningful improvements in treatment outcomes may be attainable with the introduction of new medicines. Anadys is preparing to initiate a Phase IIb study of ANA598, the Company's direct-acting antiviral or DAA, added to current standard of care for the treatment of hepatitis C. The Company is also preparing to resume clinical development of ANA773, the Company's oral, small-molecule inducer of endogenous interferons that acts via the Toll like receptor 7, or TLR7, pathway in hepatitis C.
Safe Harbor Statement
Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to (i) the plans and trial design for the planned ANA598 Phase IIb study; (ii) the belief that the preclinical properties of ANA598 support investigation of combinations with other direct antivirals and the ability to pursue such combinations; (iii) assessments of the potency, safety and tolerability profile of ANA598 based on the 12 week results; (iv) the durability of antiviral response after treatment with ANA598 is concluded as well as interim SVR rates based on data available to date; and (v) the beneficial effect of ANA598 in both CC and non-CC patients based on observations in the Phase II combination study. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical and early clinical studies may not be predictive of future results, and Anadys cannot provide any assurances that ANA598 or ANA773 will not have unforeseen safety issues, will have favorable results in future clinical trials or will receive regulatory approval. In addition, Anadys' results may be affected by competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to enter into transactions around its product candidates, its ability to successfully develop and market products, difficulties or delays in its preclinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-K for the year ended December 31, 2009, Form 10-Q for the quarter ended September 30, 2010 and Form 8-K filed on October 15, 2010. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
Pegasys® and Copegus® are registered trademarks of Hoffman-La Roche Inc.
SOURCE Anadys Pharmaceuticals, Inc.
RELATED LINKS
http://www.anadyspharma.com/
Source
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