April 02, 2011 03:30 AM Eastern Daylight Time
- Phase 2 clinical trial expected to begin in second quarter 2011-
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) announced today the presentation of data from a four-week Phase 1 clinical trial of IMO-2125 in combination with ribavirin in treatment-naïve patients chronically infected with hepatitis C virus (HCV) genotype 1. During the four weeks of treatment, IMO-2125 in combination with ribavirin was well tolerated and produced clinically meaningful antiviral activity. IMO-2125 is a Toll-like Receptor 9 (TLR9) agonist that stimulates production of natural interferons and other antiviral cytokines. The presentation (Abstract #1209), entitled “IMO-2125 plus ribavirin gives substantial first-dose viral load reductions, cumulative antiviral effect, is well tolerated in naïve genotype 1 HCV patients: a Phase 1 trial”, was made at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) being held in Berlin, Germany from March 30 – April 3, 2011. The presentation provided additional detail from the trial for which interim data was announced in December 2010.
“This study provides several key results that support our IMO-2125 development program,” said Robert Arbeit, M.D., Vice President of Clinical Development at Idera. “First, IMO-2125 in combination with ribavirin had substantial antiviral activity in treatment-naïve patients. This antiviral activity was associated with decreases in serum liver enzyme levels over the four-week course of treatment. Second, IMO-2125 was well tolerated, and demonstrated important safety features in comparison to Pegasys® used in the control arm. These included shorter duration of flu-like symptoms and minimal hematologic toxicity, with no IMO-2125-treated patients developing neutropenia requiring intervention or platelet levels below lower limits of normal.”
Dr. Arbeit continued, “We are preparing to initiate a 12-week Phase 2 clinical trial of IMO-2125 plus ribavirin in treatment-naïve genotype 1 HCV patients in the second quarter of 2011. We expect to use data from that study to select dosages for subsequent clinical trials of IMO-2125 in combination with ribavirin and a direct acting antiviral agent.”
"We have now completed Phase 1 clinical evaluation of IMO-2125 in both treatment-naïve and null-responder HCV patients and have established that its immune stimulation mechanism of action provides clinically meaningful antiviral activity and is well tolerated,” said Tim Sullivan, Ph.D., Vice President of Development Programs and Alliance Management at Idera. "By the end of this year we expect to have completed chronic nonclinical safety studies to support further clinical development of IMO-2125 as an immune modulatory component of HCV therapy.”
"Our objective is to develop a novel immune modulator for the treatment of HCV as a potential alternative to pegylated interferons,” said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer at Idera. “We have confirmed the intended mechanism of action of IMO-2125 and are very pleased with its safety profile and antiviral activity in both null-responder and treatment-naïve HCV patients. We look forward to initiating the Phase 2 clinical trial, which we expect will provide the additional data needed to advance the clinical development of IMO-2125 and support studies in combination with direct-acting antiviral agents.”
Phase 1 Clinical Trial in Treatment-naive HCV Patients
Study Design:
In this Phase 1 clinical trial, treatment-naïve genotype 1 HCV patients received IMO-2125 by subcutaneous injection over four weeks in combination with daily oral administration of standard, weight-based doses of ribavirin in one of four treatment regimens of 12 patients each. The four regimens of IMO-2125 were 0.08, 0.16, and 0.32 mg/kg once weekly and 0.16 mg/kg twice weekly. In addition, 12 patients received Pegasys® plus ribavirin. Study endpoints of safety and antiviral activity were measured through Day 29. Upon completion of the four weeks of protocol-specified treatment, all patients received follow-on treatment with Pegasys® plus ribavirin. Under the trial protocol, final safety and antiviral assessments were taken at Day 59, four weeks after the follow-on treatment with Pegasys® plus ribavirin was initiated.
Study Results:
Patient Population
All patients were Caucasian, except one Asian patient in the 0.16 mg/kg/week IMO-2125 group; all were infected with HCV genotype 1. Additional demographic and baseline data are summarized in the following table.
Safety
• IMO-2125 was well tolerated at all dose levels in combination with ribavirin over four weeks of treatment, with no treatment-related serious adverse events and no treatment discontinuations. The most common adverse events observed in the IMO-2125 regimens were mild to moderate flu-like symptoms and injection site reactions.
• Flu-like symptoms. Among patients who received IMO-2125, flu-like symptoms consisted primarily of fever and chills with onset within approximately eight hours of dosing and of brief duration, typically lasting less than one day. In contrast, the observations for the patients receiving Pegasys® who experienced flu-like symptoms were consistent with the extensively published experiences showing that flu-like symptoms generally include malaise and fatigue, have delayed onset at one or two days after dosing, and often last two days or more.
• Neutropenia. Neutropenia (absolute neutrophil count (ANC) <1000/mm3) with IMO-2125 plus ribavirin treatment was infrequent, occurring in five of 48 patients, or 10%, at some point during the four-week treatment period. Neutropenia in patients treated with IMO-2125 plus ribavirin was transient; no patients required intervention and at Day 29 no patients had ANC <1000/mm3. Neutropenia was more common with Pegasys® plus ribavirin treatment, occurring in seven of 12 patients, or 58%. Two of these patients, or 17%, required intervention for their neutropenia and at Day 29 two additional patients had ANC <1000/mm3.
At Day 29, all 48 patients who had received IMO-2125 initiated standard of care treatment with Pegasys® plus ribavirin. At Day 59, six of these patients, or 13%, had neutrophil counts less than 1000/mm3.
• Thrombocytopenia. On Day 29, all patients treated with IMO-2125 plus ribavirin had platelet counts of 145,000/mm3 or greater. Three of the 12 patients, or 25%, treated with Pegasys® plus ribavirin had platelet counts at or below 130,000/mm3 on Day 29.
At Day 29, all 48 patients who had received IMO-2125 initiated standard of care treatment with Pegasys® plus ribavirin. At Day 59, 13 of these patients, or 26%, had platelet counts at or below 130,000/mm3.
Liver Enzyme Normalization
• Serum liver enzyme levels, AST and ALT, are generally elevated in chronic hepatitis C patients. Treatment with all dose levels of IMO-2125 plus ribavirin led to progressive reductions in group means of AST and ALT to within normal limits by the end of the fourth week of treatment. Similar reductions in AST and ALT levels were observed in patients receiving treatment with Pegasys® plus ribavirin.
Effect on HCV RNA Viral Load
• Viral load reduction after first dose. IMO-2125 at all dose levels induced declines in viral levels at 48 hours after the first dose. The mean viral load reductions at 48 hours after the first dose with the 0.16 mg/kg once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -2.5, -1.3, and -1.6 log10, respectively. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at the same time point was -1.4 log10.
• Viral load reduction after four weeks. Antiviral response was variable within all treatment groups, including Pegasys® plus ribavirin. At Day 29, in each of the IMO-2125 treatment groups at 0.16 mg/kg/week or higher and in the Pegasys® plus ribavirin group, some patients achieved greater than 4 log10 reductions in viral load and some failed to achieve even a 1 log10 reduction.
Mean viral load reductions from baseline at the mid-week evaluation in the fourth week of treatment with the 0.16 mg/kg once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -3.4, -2.0, and -3.3 log10, respectively. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at the same timepoint was -3.8 log10.
Mean viral load reductions from baseline at Day 29 with the 0.16 mg/kg once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -1.7, -0.6, and -2.4 log10, respectively. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at Day 29 was -3.4 log10.
• Prognostic factors affecting antiviral activity. Uneven distribution of negative prognostic factors, such as IL28B CT or TT genotype, high baseline IP-10, and age, contributed to the variability in antiviral activity across the treatment groups. Additional data on IL28B genotype are being collected.
See Table 2
Authors of the presentation and study investigators include Dominique Guyader, M.D., of Universite de Rennes, France, Pavel Bogomolov, M.D., of the State Institution Moscow Region named after M.F. Vladymirsky, Moscow, Russia, Zhanna Kobalava, M.D., of GOUVPO Russian Peoples’ Friendship University (City Clinical Hospital #64), Moscow, Russia, Valentin Moiseev, M.D., of GOUVPO Russian Peoples’ Friendship University (City Clinical Hospital #3), Moscow, Russia, Janos Szlavik, M.D., of Szt László Hospital, Budapest, Hungary, Béatrice Astruc, M.D., of Biotrial, Rennes, France, Istan Varkonyi, M.D., of Kenezy Hospital, Debrecen, Hungary, Tim Sullivan, Ph.D., Kerry Horgan, Alice Bexon, MBChB, and Robert Arbeit, M.D., of Idera Pharmaceuticals.
About IMO-2125
IMO-2125, a Toll-like Receptor (TLR) 9 agonist, is a novel immune modulator being developed as a component of treatment for chronic hepatitis C virus (HCV) infection. IMO-2125 is designed to stimulate the immune system, causing the body to generate natural interferons and other antiviral cytokines. IMO-2125 has been evaluated in a Phase 1 clinical trial in null-responder HCV patients as monotherapy for 4 weeks and in a Phase 1 clinical trial in treatment-naïve HCV patients in combination with ribavirin for 4 weeks.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals develops drug candidates to treat chronic hepatitis C virus infection, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. The company's proprietary drug candidates are designed to modulate specific Toll-like Receptors, which are a family of immune system receptors. Idera's pioneering DNA and RNA chemistry expertise enables us to create drug candidates for internal development and generates opportunities for multiple collaborative alliances. For more information, visit http://www.iderapharma.com/.
Idera Forward Looking Statements
This press release contains forward-looking statements concerning Idera Pharmaceuticals, Inc. that involve a number of risks and uncertainties. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words "believes," "anticipates," "plans," "expects," "estimates," "intends," "should," "could," "will," "may," and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause Idera's actual results to differ materially from those indicated by such forward-looking statements, including whether results obtained in preclinical studies and early clinical trials such as the studies and 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 Annual Report on Form 10-K for the year ended December 31, 2010 which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.
Pegasys® is a registered trademark of F. Hoffmann-La Roche Company.
Contacts
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
E-mail: tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
E-mail: cerdman@macbiocom.com
Source
April 4, 2011
EASL: New data show non-alcoholic fatty liver disease will reach epidemic status in the US
Public release date: 2-Apr-2011
Contact: Dimple Natali
easlpressoffice@cohnwolfe.com
44-797-160-8315
European Association for the Study of the Liver
Berlin, Germany, Saturday 02 April 2011: According to new data presented today at the International Liver CongressTM, the United States (U.S.) could soon be faced with an epidemic of Non-Alcoholic Fatty Liver Disease (NAFLD)1, one of the major contributing factors of chronic liver disease (CLD), considered as one of the major causes of morbidity and mortality worldwide. The study highlights that if the current rates of obesity and diabetes continue for another two decades, the prevalence of NAFLD in the US is expected to increase by 50% in 2030.
The study analysed pre-existing clinical survey data over a 10 year period (1988-1994, 1999-2004 and 2005-2008), which included 39,500 adults from three survey cycles. Over the three cycles the prevalence of NAFLD doubled from 5.51% to 11.0% respectively. Furthermore, during the first survey cycle (1988-1994) 46.8% of all CLD's was related to NAFLD but by 2005-2008 this had increased to 75.1%. In addition, the prevalence of obesity and diabetes, the two key risk factors for NAFLD also steadily increased.
Mark Thursz EASL's Vice Secretary commented: "Non-alcoholic fatty liver disease is fast becoming one of the top concerns for clinicians due to the obesity epidemic and it's potential to progress to advanced liver disease which significantly impacts on overall liver-related mortality. This data highlights a serious concern for the future, and the enormous increasing health burden of NAFLD. If the obesity epidemic is anything to go by, the U.S. NAFLD epidemic may have a ripple effect worldwide. It is imperative that health systems continue to drive effective educational programmes to reinforce awareness among the general public to alert them of the risks of obesity and promote the importance of diet and exercise".
NAFLD is the term used to describe fat build-up in liver cells in people who do not drink alcohol excessively and is the most common persistent liver disorder in Western countries with an estimated overall prevalence of 20-30%.2
NAFLD encompasses a spectrum of liver disease associated with insulin resistance, diabetes and obesity and as such people most at risk of NAFLD are those who are obese, have insulin resistance associated with diabetes, high blood pressure and cholesterol.3
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. Younossi Z et al., The Changing Face of Chronic Liver Disease (CLD) in the United States: The Rising Epidemic of Non-Alcoholic Fatty Liver Disease (NAFLD). Presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/204.htm
2. Understanding and Preventing the Progression of Liver Disease in Non-Alcoholic Fatty Liver Disease (NAFLD). Fatty Liver Inhibition of Progression (FLIP) http://www.flip-fp7.eu/. Accessed March 2011.
3. Fatty Liver. Patient UK. Available at http://www.patient.co.uk/doctor/Steatohepatitis-and-Steatosis-(Fatty-Liver).htm. Accessed March 2011.
Source
Contact: Dimple Natali
easlpressoffice@cohnwolfe.com
44-797-160-8315
European Association for the Study of the Liver
Berlin, Germany, Saturday 02 April 2011: According to new data presented today at the International Liver CongressTM, the United States (U.S.) could soon be faced with an epidemic of Non-Alcoholic Fatty Liver Disease (NAFLD)1, one of the major contributing factors of chronic liver disease (CLD), considered as one of the major causes of morbidity and mortality worldwide. The study highlights that if the current rates of obesity and diabetes continue for another two decades, the prevalence of NAFLD in the US is expected to increase by 50% in 2030.
The study analysed pre-existing clinical survey data over a 10 year period (1988-1994, 1999-2004 and 2005-2008), which included 39,500 adults from three survey cycles. Over the three cycles the prevalence of NAFLD doubled from 5.51% to 11.0% respectively. Furthermore, during the first survey cycle (1988-1994) 46.8% of all CLD's was related to NAFLD but by 2005-2008 this had increased to 75.1%. In addition, the prevalence of obesity and diabetes, the two key risk factors for NAFLD also steadily increased.
Mark Thursz EASL's Vice Secretary commented: "Non-alcoholic fatty liver disease is fast becoming one of the top concerns for clinicians due to the obesity epidemic and it's potential to progress to advanced liver disease which significantly impacts on overall liver-related mortality. This data highlights a serious concern for the future, and the enormous increasing health burden of NAFLD. If the obesity epidemic is anything to go by, the U.S. NAFLD epidemic may have a ripple effect worldwide. It is imperative that health systems continue to drive effective educational programmes to reinforce awareness among the general public to alert them of the risks of obesity and promote the importance of diet and exercise".
NAFLD is the term used to describe fat build-up in liver cells in people who do not drink alcohol excessively and is the most common persistent liver disorder in Western countries with an estimated overall prevalence of 20-30%.2
NAFLD encompasses a spectrum of liver disease associated with insulin resistance, diabetes and obesity and as such people most at risk of NAFLD are those who are obese, have insulin resistance associated with diabetes, high blood pressure and cholesterol.3
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. Younossi Z et al., The Changing Face of Chronic Liver Disease (CLD) in the United States: The Rising Epidemic of Non-Alcoholic Fatty Liver Disease (NAFLD). Presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/204.htm
2. Understanding and Preventing the Progression of Liver Disease in Non-Alcoholic Fatty Liver Disease (NAFLD). Fatty Liver Inhibition of Progression (FLIP) http://www.flip-fp7.eu/. Accessed March 2011.
3. Fatty Liver. Patient UK. Available at http://www.patient.co.uk/doctor/Steatohepatitis-and-Steatosis-(Fatty-Liver).htm. Accessed March 2011.
Source
EASL: First Vaccine for Viral Hepatitis C Could Become a Reality
ScienceDaily (Apr. 1, 2011) — Early data from phase I trials of an HCV vaccine presented April 1 at the International Liver Congress show encouraging results, with high immunogenicity and good safety profile.
In the first study, a therapeutic T-cell vaccine, based on novel adenoviral vectors was used on a small population of treatment naive patients with chronic genotype 1 HCV infection. Intra-muscular vaccination was administered 2 or 14 weeks into a 48-week course of treatment with Peg-IFNa2a/ribavirin. 50% of vaccinated patients had CD4+ and CD8+ HCV specific T-cell responses as detected by ELISpot at 2-8 weeks post boost, showing a strong immunogenicity for the vaccine. Local and systemic adverse events to vaccination were mild, with no evidence of liver immunopathology (measured by liver transaminase levels).
The second study looked at the potential for a prophylactic vaccine based on similar novel adenoviral vectors technology (replicative-defective human Ad6 and a novel simian AdCh3 vector that encode 1985 amino-acids derived from the NS3-5 region of a genotype-1b strain). 27 healthy volunteers were vaccinated following a double prime, heterologous boost strategy. The vaccine induced polyfunctional CD4+ and CD8+ T cells responses which were maintained up to 52 weeks post prime. Overall vaccination was very well tolerated with mild/moderate local and systemic reactions and no serious adverse advents.
Professor Heiner Wedemeyer, EASL's Secretary General commented: "Vaccines are an exciting area of research now with the potential to add to the range of treatments available for patients with chronic viral hepatitis. These are early data but results are very encouraging indeed and as experts, we look forward to more scientific evidence being made available to support this new technology as a future treatment option as well as potentially preventing infection."
Previous research and data presented at the International Liver Congress shows that vaccination with adenoviral vectors induced highly potent and durable T-cell responses in healthy human and that similar vectors may prevent chronic infection in animals.3 This is the first time the immunogenicity and safety of vaccination was tested on HCV patients and healthy subjects.
Source
In the first study, a therapeutic T-cell vaccine, based on novel adenoviral vectors was used on a small population of treatment naive patients with chronic genotype 1 HCV infection. Intra-muscular vaccination was administered 2 or 14 weeks into a 48-week course of treatment with Peg-IFNa2a/ribavirin. 50% of vaccinated patients had CD4+ and CD8+ HCV specific T-cell responses as detected by ELISpot at 2-8 weeks post boost, showing a strong immunogenicity for the vaccine. Local and systemic adverse events to vaccination were mild, with no evidence of liver immunopathology (measured by liver transaminase levels).
The second study looked at the potential for a prophylactic vaccine based on similar novel adenoviral vectors technology (replicative-defective human Ad6 and a novel simian AdCh3 vector that encode 1985 amino-acids derived from the NS3-5 region of a genotype-1b strain). 27 healthy volunteers were vaccinated following a double prime, heterologous boost strategy. The vaccine induced polyfunctional CD4+ and CD8+ T cells responses which were maintained up to 52 weeks post prime. Overall vaccination was very well tolerated with mild/moderate local and systemic reactions and no serious adverse advents.
Professor Heiner Wedemeyer, EASL's Secretary General commented: "Vaccines are an exciting area of research now with the potential to add to the range of treatments available for patients with chronic viral hepatitis. These are early data but results are very encouraging indeed and as experts, we look forward to more scientific evidence being made available to support this new technology as a future treatment option as well as potentially preventing infection."
Previous research and data presented at the International Liver Congress shows that vaccination with adenoviral vectors induced highly potent and durable T-cell responses in healthy human and that similar vectors may prevent chronic infection in animals.3 This is the first time the immunogenicity and safety of vaccination was tested on HCV patients and healthy subjects.
Source
EASL: Boceprevir Plays Well With Interferon Drugs
By Walter Alexander, Contributing Writer, MedPage Today Published: April 02, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
BERLIN -- Boceprevir, an investigational protease inhibitor for hepatitis C virus (HCV) infection, is effective against genotype 1 of the virus irrespective of the particular type of pegylated interferon alfa drug with which it is combined, a researcher said here.
In two studies just published in the New England Journal of Medicine, triple therapy including boceprevir (Victrelis) improved outcomes both in previously untreated patients and in those with inadequate responses to standard therapy, in comparison with standard two-drug therapy.
But both studies used peginterferon alfa-2b along with ribavirin as two-drug regimen, leaving open the question of whether boceprevir would be equally effective when used with peginterferon alfa-2a, the other major type of interferon drug for HCV.
In a late-breaking poster presentation here at the European Association for the Study of the Liver (EASL) annual meeting, a researcher from Northwestern University in Chicago reported response rates with "PEG2a" and boceprevir in prior nonresponders that were similar to those seen in the so-called RESPOND-2 trial reported in the NEJM with the 2b version.
"PEG2a is used throughout the world, too," the researcher, Steven Flamm, MD, told MedPage Today. "This is the first large-scale trial to look at boceprevir with PEG2a. It's important to establish that boceprevir also works with this other pegylated product."
The study he reported involved 201 patients with HCV genotype 1 who had relapsed or failed to maintain responses with previous interferon and ribavirin therapy.
They were randomized in a 2:1 ratio to two arms: 134 to receive a four-week lead-in of pegylated interferon alfa-2a and ribavirin with boceprevir then added for 44 weeks, and 67 to a control regimen with the same schedule but with placebo in place of boceprevir.
Patients with detectable HCV-RNA at week 12 were discontinued from treatment for futility. The study's primary endpoint was sustained viral response at 24-weeks post therapy.
Significantly more patients achieved a sustained response in the boceprevir group: 64% versus 21% in the control group (P<0.0001), nearly identical to the RESPOND-2 findings. The relapse rate was higher in the control group, at 33% versus 12% (P not reported).
Flamm also reported that viral response at eight weeks (defined as undetectable HCV RNA) strongly predicted a sustained response. In patients with early responses, sustained response rates were 89% with boceprevir versus 44% in the control group.
On the other hand, sustained response rates were poorer for patients failing to achieve undetectable viral load at eight weeks, with rates of 42% with boceprevir and 16% in the control group.
Compared with the control group, patients in the boceprevir arm were about twice as likely to suffer serious anemia or neutropenia, with higher rates of erythropoietin use as well.
Discontinuations and dose modifications because of adverse events were more common among patients taking boceprevir. But futility by week 12 was even more common in the control group.
As a result, the overall proportion of patients remaining on treatment at week 20 was substantially lower in the control arm -- 31% versus 72% -- and the median duration of treatment was 334 days in the boceprevir group compared with 105 days for controls.
Flamm underscored that HCV genotype 1 is the most common and least responsive form of HCV, and that in this population the standard-of-care treatment is usually a failure. "Many of these people are desperate, and there's nothing else we can do for them until we have a new treatment," he said.
He concluded, "Boceprevir is safe and effective with both peginterferon alfa-2a and 2b."
Mark Thursz, MD, a hepatologist at Imperial College in London and vice-secretary of EASL, told MedPage Today that the 2a form is the more commonly used peginterferon in Great Britain and Europe.
"It was necessary to show that boceprevir works with both interferons," he said.
The study was supported by Merck.
Flamm reported relationships with Amgen, Genzyme, and Schering-Plough (now Merck). Several co-authors were Merck employees.
Thursz declared he had no relevant financial relationships.
Primary source: European Association for the Study of the Liver
Source reference:
Flamm S, et al "High sustained virologic response (SVR) among genotype 1 previous non-responders and relapsers to peginterferon/ribavirin when re-treated with boceprevir (BOC) plus peginterferon alfa-2a/ribavirin" EASL 2011; Abstract 4.
Source
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
BERLIN -- Boceprevir, an investigational protease inhibitor for hepatitis C virus (HCV) infection, is effective against genotype 1 of the virus irrespective of the particular type of pegylated interferon alfa drug with which it is combined, a researcher said here.
In two studies just published in the New England Journal of Medicine, triple therapy including boceprevir (Victrelis) improved outcomes both in previously untreated patients and in those with inadequate responses to standard therapy, in comparison with standard two-drug therapy.
But both studies used peginterferon alfa-2b along with ribavirin as two-drug regimen, leaving open the question of whether boceprevir would be equally effective when used with peginterferon alfa-2a, the other major type of interferon drug for HCV.
In a late-breaking poster presentation here at the European Association for the Study of the Liver (EASL) annual meeting, a researcher from Northwestern University in Chicago reported response rates with "PEG2a" and boceprevir in prior nonresponders that were similar to those seen in the so-called RESPOND-2 trial reported in the NEJM with the 2b version.
"PEG2a is used throughout the world, too," the researcher, Steven Flamm, MD, told MedPage Today. "This is the first large-scale trial to look at boceprevir with PEG2a. It's important to establish that boceprevir also works with this other pegylated product."
The study he reported involved 201 patients with HCV genotype 1 who had relapsed or failed to maintain responses with previous interferon and ribavirin therapy.
They were randomized in a 2:1 ratio to two arms: 134 to receive a four-week lead-in of pegylated interferon alfa-2a and ribavirin with boceprevir then added for 44 weeks, and 67 to a control regimen with the same schedule but with placebo in place of boceprevir.
Patients with detectable HCV-RNA at week 12 were discontinued from treatment for futility. The study's primary endpoint was sustained viral response at 24-weeks post therapy.
Significantly more patients achieved a sustained response in the boceprevir group: 64% versus 21% in the control group (P<0.0001), nearly identical to the RESPOND-2 findings. The relapse rate was higher in the control group, at 33% versus 12% (P not reported).
Flamm also reported that viral response at eight weeks (defined as undetectable HCV RNA) strongly predicted a sustained response. In patients with early responses, sustained response rates were 89% with boceprevir versus 44% in the control group.
On the other hand, sustained response rates were poorer for patients failing to achieve undetectable viral load at eight weeks, with rates of 42% with boceprevir and 16% in the control group.
Compared with the control group, patients in the boceprevir arm were about twice as likely to suffer serious anemia or neutropenia, with higher rates of erythropoietin use as well.
Discontinuations and dose modifications because of adverse events were more common among patients taking boceprevir. But futility by week 12 was even more common in the control group.
As a result, the overall proportion of patients remaining on treatment at week 20 was substantially lower in the control arm -- 31% versus 72% -- and the median duration of treatment was 334 days in the boceprevir group compared with 105 days for controls.
Flamm underscored that HCV genotype 1 is the most common and least responsive form of HCV, and that in this population the standard-of-care treatment is usually a failure. "Many of these people are desperate, and there's nothing else we can do for them until we have a new treatment," he said.
He concluded, "Boceprevir is safe and effective with both peginterferon alfa-2a and 2b."
Mark Thursz, MD, a hepatologist at Imperial College in London and vice-secretary of EASL, told MedPage Today that the 2a form is the more commonly used peginterferon in Great Britain and Europe.
"It was necessary to show that boceprevir works with both interferons," he said.
The study was supported by Merck.
Flamm reported relationships with Amgen, Genzyme, and Schering-Plough (now Merck). Several co-authors were Merck employees.
Thursz declared he had no relevant financial relationships.
Primary source: European Association for the Study of the Liver
Source reference:
Flamm S, et al "High sustained virologic response (SVR) among genotype 1 previous non-responders and relapsers to peginterferon/ribavirin when re-treated with boceprevir (BOC) plus peginterferon alfa-2a/ribavirin" EASL 2011; Abstract 4.
Source
EASL: Telaprevir Helps in Prior HCV Tx Failures
By Walter Alexander, Contributing Writer, MedPage Today
Published: April 01, 2011
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
BERLIN -- Adding telaprevir, an investigational oral protease inhibitor, to peginterferon alfa-2a and ribavirin substantially increased sustained response rates in patients with genotype 1 hepatitis C virus (HCV) infection who had previously failed the standard therapy, a researcher said here.
Results from the phase III REALIZE trial indicated that, among prior relapsers, sustained response rates with two telaprevir-containing regimens were 83% and 88%, compared with 24% for peginterferon alfa-2a and ribavirin plus placebo (both P<0.001), reported Stefan Zeuzem, MD, of Johann Wolfgang Goethe University Medical Center in Frankfurt am Main, Germany.
Lower sustained viral response rates were seen in patients who previously showed partial or no response to the two standard drugs, but they were still significantly better than in the placebo group (41% in both telaprevir arms versus 9% in the control group, P<0.001).
Zeuzem presented the findings here at the European Association for the Study of the Liver (EASL) annual meeting.
"T plus P plus R was superior to P plus R alone in treatment-experienced populations including prior relapsers, partial responders, and null responders," he told attendees.
The findings confirm those of earlier studies, including one reported last year in the New England Journal of Medicine.
The current standard of care for HCV is the combination of peginterferon alfa-2a and ribavirin, Zeuzem explained, but it fails to achieved sustained viral responses in 60% of patients with HCV genotype 1.
REALIZE assigned 662 patients to three treatment arms in a 2:2:1 ratio:
• T12/PR48: Telaprevir, peginterferon, and ribavirin for 12 weeks followed by placebo plus peginterferon and ribavirin for four weeks and then the two standard drugs alone for 32 weeks
• LIT12/PR48: Placebo plus peginterferon and ribavirin for four weeks, followed by telaprevir and the standard drugs for 12 weeks, and then the standard drugs alone for 32 weeks
• Pbo/PR48: 48 weeks of peginterferon plus ribavirin, with placebo for the first 16 weeks
The REALIZE primary endpoint was the proportion of these patients achieving sustained viral responses, defined as undetectable plasma HCV RNA at 24 weeks after the last planned intake of study medication. Whether the four-week lead-in with standard therapy alone made a difference in responses was a secondary objective.
Telaprevir was given at 750 mg every eight hours. Standard doses of the other drugs were used (180 mcg/week for peginterferon, 1,000 to 1,200 mg/day for ribavirin).
Null responders, partial responders, and relapsers to previous peginterferon plus ribavirin constituted about 28%, 19%, and 54%, respectively, of the cohort. Nearly half of patients were in advanced stages of disease; 89% had a baseline HCV viral load of >800,000 IU/mL. Median age was about 51 and more than two-thirds were men.
Sustained viral responses were seen in 83% of the T12/PR48 group and 88% of the LIT12/PR48 patients versus 24% of the Pbo/PR48 group.
These results, Zeuzem pointed out, indicated that the four-week lead-in with standard therapy did not improve response rates compared with including telaprevir from the outset.
Responses rates of 41% were seen in the previous null or partial responders in both the T12/PR48 and LIT12/PR48 groups, compared with just 9% of the previously unresponsive Pbo/PR48 patients.
Zeuzem said that sustained response rates were higher for prior partial responders than for prior null responders.
Relapse rates were 10% each for the two telaprevir-containing arms and 23% for the Pbo/PR48 arm.
Among the most common adverse events during any treatment phase, fatigue occurred in 55% of the T12/PR48 patients, 50% of the LIT12/PR48 group, and 40% of the Pbo/PR48 group. Frequencies of pruritus were similar.
Anorectal symptoms (anal pruritus, anorectal discomfort, hemorrhoids) were reported in 28%, 22%, and 8% of the T12/PR48, LIT12/PR48, and Pbo/PR48 groups, respectively.
For each of these adverse events, and for anemia, rash, nausea and diarrhea, the incidence was more than 10% greater in the T12/PR48 arm than in the Pbo/PR48 arm.
Discontinuations of any study drug during telaprevir treatment occurred in 29% of patients. Rash and anemia were the most common adverse effects associated with drug stoppage.
"These are really exciting results for this particularly difficult-to-treat group of patients," commented Mark Thursz, MD, a hepatologist at Imperial College in London and vice-secretary of the EASL.
"Over 60% achieved an SVR. Compared with patients who previously relapsed after P-plus-R treatment, those who are partial responders did less well, and the null group was disappointing, but that was not entirely surprising."
A marketing application for telaprevir has been filed with the FDA, which is giving it priority review. The agency's deadline for a decision is May 23.
Zeuzem disclosed relationships with Abbott, Achillion, Anadys, BMS, Gilead, iTherX, Merck, Novartis, Pfizer, Pharmasset, Roche, Santaris, Tibotec, and Vertex.
Thursz declared he had no relevant industry relationships.
Primary source: European Association for the Study of the Liver
Source reference:
Zeuzem S, et al "REALIZE trial final results: telaprevir-based regimen for genotype 1 hepatitis C virus infection in patients with prior null response, partial response or relapse to peginterferon/ribavirin" EASL 2011; Abstract 192.
Source
Published: April 01, 2011
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
BERLIN -- Adding telaprevir, an investigational oral protease inhibitor, to peginterferon alfa-2a and ribavirin substantially increased sustained response rates in patients with genotype 1 hepatitis C virus (HCV) infection who had previously failed the standard therapy, a researcher said here.
Results from the phase III REALIZE trial indicated that, among prior relapsers, sustained response rates with two telaprevir-containing regimens were 83% and 88%, compared with 24% for peginterferon alfa-2a and ribavirin plus placebo (both P<0.001), reported Stefan Zeuzem, MD, of Johann Wolfgang Goethe University Medical Center in Frankfurt am Main, Germany.
Lower sustained viral response rates were seen in patients who previously showed partial or no response to the two standard drugs, but they were still significantly better than in the placebo group (41% in both telaprevir arms versus 9% in the control group, P<0.001).
Zeuzem presented the findings here at the European Association for the Study of the Liver (EASL) annual meeting.
"T plus P plus R was superior to P plus R alone in treatment-experienced populations including prior relapsers, partial responders, and null responders," he told attendees.
The findings confirm those of earlier studies, including one reported last year in the New England Journal of Medicine.
The current standard of care for HCV is the combination of peginterferon alfa-2a and ribavirin, Zeuzem explained, but it fails to achieved sustained viral responses in 60% of patients with HCV genotype 1.
REALIZE assigned 662 patients to three treatment arms in a 2:2:1 ratio:
• T12/PR48: Telaprevir, peginterferon, and ribavirin for 12 weeks followed by placebo plus peginterferon and ribavirin for four weeks and then the two standard drugs alone for 32 weeks
• LIT12/PR48: Placebo plus peginterferon and ribavirin for four weeks, followed by telaprevir and the standard drugs for 12 weeks, and then the standard drugs alone for 32 weeks
• Pbo/PR48: 48 weeks of peginterferon plus ribavirin, with placebo for the first 16 weeks
The REALIZE primary endpoint was the proportion of these patients achieving sustained viral responses, defined as undetectable plasma HCV RNA at 24 weeks after the last planned intake of study medication. Whether the four-week lead-in with standard therapy alone made a difference in responses was a secondary objective.
Telaprevir was given at 750 mg every eight hours. Standard doses of the other drugs were used (180 mcg/week for peginterferon, 1,000 to 1,200 mg/day for ribavirin).
Null responders, partial responders, and relapsers to previous peginterferon plus ribavirin constituted about 28%, 19%, and 54%, respectively, of the cohort. Nearly half of patients were in advanced stages of disease; 89% had a baseline HCV viral load of >800,000 IU/mL. Median age was about 51 and more than two-thirds were men.
Sustained viral responses were seen in 83% of the T12/PR48 group and 88% of the LIT12/PR48 patients versus 24% of the Pbo/PR48 group.
These results, Zeuzem pointed out, indicated that the four-week lead-in with standard therapy did not improve response rates compared with including telaprevir from the outset.
Responses rates of 41% were seen in the previous null or partial responders in both the T12/PR48 and LIT12/PR48 groups, compared with just 9% of the previously unresponsive Pbo/PR48 patients.
Zeuzem said that sustained response rates were higher for prior partial responders than for prior null responders.
Relapse rates were 10% each for the two telaprevir-containing arms and 23% for the Pbo/PR48 arm.
Among the most common adverse events during any treatment phase, fatigue occurred in 55% of the T12/PR48 patients, 50% of the LIT12/PR48 group, and 40% of the Pbo/PR48 group. Frequencies of pruritus were similar.
Anorectal symptoms (anal pruritus, anorectal discomfort, hemorrhoids) were reported in 28%, 22%, and 8% of the T12/PR48, LIT12/PR48, and Pbo/PR48 groups, respectively.
For each of these adverse events, and for anemia, rash, nausea and diarrhea, the incidence was more than 10% greater in the T12/PR48 arm than in the Pbo/PR48 arm.
Discontinuations of any study drug during telaprevir treatment occurred in 29% of patients. Rash and anemia were the most common adverse effects associated with drug stoppage.
"These are really exciting results for this particularly difficult-to-treat group of patients," commented Mark Thursz, MD, a hepatologist at Imperial College in London and vice-secretary of the EASL.
"Over 60% achieved an SVR. Compared with patients who previously relapsed after P-plus-R treatment, those who are partial responders did less well, and the null group was disappointing, but that was not entirely surprising."
A marketing application for telaprevir has been filed with the FDA, which is giving it priority review. The agency's deadline for a decision is May 23.
Zeuzem disclosed relationships with Abbott, Achillion, Anadys, BMS, Gilead, iTherX, Merck, Novartis, Pfizer, Pharmasset, Roche, Santaris, Tibotec, and Vertex.
Thursz declared he had no relevant industry relationships.
Primary source: European Association for the Study of the Liver
Source reference:
Zeuzem S, et al "REALIZE trial final results: telaprevir-based regimen for genotype 1 hepatitis C virus infection in patients with prior null response, partial response or relapse to peginterferon/ribavirin" EASL 2011; Abstract 192.
Source
EASL: Sustained viral response achieved in 83% of hepatitis C infected patients with new HCV protease inhibitor from Boehringer Ingelheim
April 01, 2011 10:07 AM Eastern Daylight Time
Final results from two clinical Phase IIb studies presented at EASL 2011 demonstrate up to 83% SVR in treatment naïve HCV patients and up to 41% in previously unsuccessfully treated patients, respectively
BERLIN & INGELHEIM, Germany--(BUSINESS WIRE)--New data presented today at the International Liver CongressTM 2011, the 46th Annual Meeting of the European Association for the Study of the Liver (EASL), in Berlin, highlighted the efficacy of Boehringer Ingelheim’s once-daily oral protease inhibitor BI 201335, in both treatment-naïve and -experienced patients with chronic genotype-1 hepatitis C virus (HCV) infection. Genotype-1 HCV is the most challenging genotype of HCV to treat.
Results from SILEN-C1 trial show high rates of sustained viral response (SVR, which is considered viral cure) in patients with no previous treatments, who received either 120mg or 240mg BI 201335 once-daily plus the current standard-of-care (SOC), i.e. pegylated interferon (PegIFN) and ribavirin (RBV). Up to 87% of patients were able to shorten overall treatment duration from 48 to 24 weeks.
In the SILEN-C2 trial, in non-responding patients, the 240mg dose of BI 201335 once daily also achieved impressive results in a population that has not responded to SOC, and achieved such without a lead in therapy.
“The final results from the SILEN-C1 and 2 trials have demonstrated the high potential for excellent efficacy of this once daily protease inhibitor in a broad range of HCV patients,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. “The current standard-of-care in HCV is not effective for many patients. The viral cure rates achieved by protease inhibitors such as BI 201335 highlight the possibility to improve treatment outcomes as well as the option to shorten the overall treatment duration for the majority of HCV patients.”
“Boehringer Ingelheim is continuing its long heritage in virology and is dedicated to developing new medicines to improve treatment for HCV patients,” continued Professor Klaus Dugi. “BI 201335 is part of our robust HCV portfolio that we are investigating with the goal of improving current treatment and ultimately paving a path for a simpler, more effective and better tolerated HCV therapy.”
Study Details:
(Oral Presentation at EASL, Parallel Session: HCV Drug Development, 16:00h-16:15h, Abstract 60) SILEN-C1: Sustained Virologic Response (SVR) and Safety of BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin in Treatment-Naïve Patients with Chronic Genotype-1 HCV Infection
The Phase II SILEN-C1 study results show BI 201335 to have strong antiviral activity, with overall SVR rates reaching 83% in the 240mg once-daily group (plus current SOC). Of the patients achieving extended rapid viral response (eRVR, defined as plasma viral load less than 25 IU/ml at week 4 and undetectable at weeks 8-20), 93% achieved SVR with 24 weeks of SOC (PegIFN/RBV) treatment.
In addition to high efficacy at all dose levels, BI 201335 once daily with SOC also demonstrated good tolerability and safety:
The most frequent dose-dependent adverse events in BI 201335 treatment groups were mild gastrointestinal disorders, mild rash or photosensitivity and jaundice resulting from isolated unconjugated hyperbilirubinaemia. Average alanine aminotransferase (ALT) improved in all BI 201335 groups compared to placebo. Of note, there was no excess anaemia reported in the active groups compared to SOC. Phase III trials of BI 201335 are in preparation.
(Oral Presentation at EASL Parallel Session: HCV Drug Development, 17:30h-17:45h, Abstract 66) SILEN-C2: Sustained Virologic Response and Safety of BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin in Chronic HCV Genotype-1 Patients with Non-Response to PegIFN/RBV
The Phase II SILEN-C2 study evaluated the virological response and safety of different doses of BI 201335 in treatment-experienced patients who did not respond to at least 12 weeks of prior treatment with PegIFN/RBV. The results demonstrate that treatment with BI 201335 once daily at 240mg, plus SOC provides high efficacy and good tolerability in this very difficult-to-treat patient population, with 41% achieving SVR. As is seen in SILEN-C1, a 3-day lead in with SOC was associated with decreased viral response. Phase III trials of BI 201335 are in preparation.
The most frequent dose-dependent adverse events in BI 201335 treatment groups were similar to those seen in SILEN-C1. Serious or severe adverse events were reported more frequently in the BI 201335 240mg BID with lead in (LI) group.
NOTES TO EDITORS
Additional BI 201335 Studies to be Presented at EASL
• SVR and pharmacokinetics of the HCV protease inhibitor BI 201335 with PegIFN/RBV in HCV genotype-1 patients with compensated liver cirrhosis and non-response to previous PegIFN/RBV (Poster 1231. S. Pol, et al.)
• Mechanisms of isolated unconjugated hyperbilirubinaemia induced by the HCV NS3/4A protease inhibitor BI 201335 (Poster 1236. R. Sane, et al.)
• BI 201335 pharmacokinetics and early effect on viral load in HCV genotype-1 patients (Poster 1249. C. Yong, et al.)
• Preclinical characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BILB 1941 (Poster 1215. G. Kukolj et. al.)
Posters are presented on Saturday, 2 April, 2011, 09:00h - 18:00h.
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 cause 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 suspension, 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 programme supports the investigation of BI 201335 in Phase III trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Phase II trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.
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/
www.twitter.com/boehringer
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
Final results from two clinical Phase IIb studies presented at EASL 2011 demonstrate up to 83% SVR in treatment naïve HCV patients and up to 41% in previously unsuccessfully treated patients, respectively
BERLIN & INGELHEIM, Germany--(BUSINESS WIRE)--New data presented today at the International Liver CongressTM 2011, the 46th Annual Meeting of the European Association for the Study of the Liver (EASL), in Berlin, highlighted the efficacy of Boehringer Ingelheim’s once-daily oral protease inhibitor BI 201335, in both treatment-naïve and -experienced patients with chronic genotype-1 hepatitis C virus (HCV) infection. Genotype-1 HCV is the most challenging genotype of HCV to treat.
Results from SILEN-C1 trial show high rates of sustained viral response (SVR, which is considered viral cure) in patients with no previous treatments, who received either 120mg or 240mg BI 201335 once-daily plus the current standard-of-care (SOC), i.e. pegylated interferon (PegIFN) and ribavirin (RBV). Up to 87% of patients were able to shorten overall treatment duration from 48 to 24 weeks.
In the SILEN-C2 trial, in non-responding patients, the 240mg dose of BI 201335 once daily also achieved impressive results in a population that has not responded to SOC, and achieved such without a lead in therapy.
“The final results from the SILEN-C1 and 2 trials have demonstrated the high potential for excellent efficacy of this once daily protease inhibitor in a broad range of HCV patients,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. “The current standard-of-care in HCV is not effective for many patients. The viral cure rates achieved by protease inhibitors such as BI 201335 highlight the possibility to improve treatment outcomes as well as the option to shorten the overall treatment duration for the majority of HCV patients.”
“Boehringer Ingelheim is continuing its long heritage in virology and is dedicated to developing new medicines to improve treatment for HCV patients,” continued Professor Klaus Dugi. “BI 201335 is part of our robust HCV portfolio that we are investigating with the goal of improving current treatment and ultimately paving a path for a simpler, more effective and better tolerated HCV therapy.”
Study Details:
(Oral Presentation at EASL, Parallel Session: HCV Drug Development, 16:00h-16:15h, Abstract 60) SILEN-C1: Sustained Virologic Response (SVR) and Safety of BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin in Treatment-Naïve Patients with Chronic Genotype-1 HCV Infection
The Phase II SILEN-C1 study results show BI 201335 to have strong antiviral activity, with overall SVR rates reaching 83% in the 240mg once-daily group (plus current SOC). Of the patients achieving extended rapid viral response (eRVR, defined as plasma viral load less than 25 IU/ml at week 4 and undetectable at weeks 8-20), 93% achieved SVR with 24 weeks of SOC (PegIFN/RBV) treatment.
In addition to high efficacy at all dose levels, BI 201335 once daily with SOC also demonstrated good tolerability and safety:
The most frequent dose-dependent adverse events in BI 201335 treatment groups were mild gastrointestinal disorders, mild rash or photosensitivity and jaundice resulting from isolated unconjugated hyperbilirubinaemia. Average alanine aminotransferase (ALT) improved in all BI 201335 groups compared to placebo. Of note, there was no excess anaemia reported in the active groups compared to SOC. Phase III trials of BI 201335 are in preparation.
(Oral Presentation at EASL Parallel Session: HCV Drug Development, 17:30h-17:45h, Abstract 66) SILEN-C2: Sustained Virologic Response and Safety of BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin in Chronic HCV Genotype-1 Patients with Non-Response to PegIFN/RBV
The Phase II SILEN-C2 study evaluated the virological response and safety of different doses of BI 201335 in treatment-experienced patients who did not respond to at least 12 weeks of prior treatment with PegIFN/RBV. The results demonstrate that treatment with BI 201335 once daily at 240mg, plus SOC provides high efficacy and good tolerability in this very difficult-to-treat patient population, with 41% achieving SVR. As is seen in SILEN-C1, a 3-day lead in with SOC was associated with decreased viral response. Phase III trials of BI 201335 are in preparation.
The most frequent dose-dependent adverse events in BI 201335 treatment groups were similar to those seen in SILEN-C1. Serious or severe adverse events were reported more frequently in the BI 201335 240mg BID with lead in (LI) group.
NOTES TO EDITORS
Additional BI 201335 Studies to be Presented at EASL
• SVR and pharmacokinetics of the HCV protease inhibitor BI 201335 with PegIFN/RBV in HCV genotype-1 patients with compensated liver cirrhosis and non-response to previous PegIFN/RBV (Poster 1231. S. Pol, et al.)
• Mechanisms of isolated unconjugated hyperbilirubinaemia induced by the HCV NS3/4A protease inhibitor BI 201335 (Poster 1236. R. Sane, et al.)
• BI 201335 pharmacokinetics and early effect on viral load in HCV genotype-1 patients (Poster 1249. C. Yong, et al.)
• Preclinical characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BILB 1941 (Poster 1215. G. Kukolj et. al.)
Posters are presented on Saturday, 2 April, 2011, 09:00h - 18:00h.
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 cause 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 suspension, 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 programme supports the investigation of BI 201335 in Phase III trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Phase II trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.
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/
www.twitter.com/boehringer
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
EASL: Phase III Data Suggests IL28B Genotyping Helps Predict Response to Merck & Co.’s HCV Drug
GEN News Highlights: Apr 1, 2011
New analyses of Phase III trial data suggests that identifying HCV patients’ IL28B status and evaluating their initial response to peginterferon alfa-2b and ribavirin (PR) therapy can help predict those who will achieve a sustained virologic response (SVR) when Merck & Co.’s oral protease inhibitor candidate Victrelis® (boceprivir) is subsequently added to the treatment mix.
The new analyses, presented at the International Liver Congress/46th European Association for the Study of Liver (EASL) annual meeting, coincided with publication in The New England Journal of Medicine of data from the Phase III HCV Respond-2 and HCV Sprint-2 studies evaluating Vectrelis combined with PR in patients who had failed prior PR therapy and who were new to treatment, respectively. Both trials formed part of the regulatory submissions for Victrelis, which were accepted for accelerated review by both FDA and the EMA in January.
The new data presented at EASL emerged from additional analyses of both the Respond-2 and Sprint-2 studies. In the Sprint-2 treatment-naïve study, patients receiving Victrelis who had good response to PR therapy after the four-week lead-in period achieved SVR rates of 79% over the 48-week treatment period. The SVR rate for patients in the PR therapy control arm who initially responded well to PR therapy was 51%. Among patients with poor response after the four-week lead-in, the SVR rate was 38% for Vicrelis-treated patients in the 48-week treatment arm compared with an SVR rate of 4% in the PR control arm.
In the Respond-2 treatment-failure study, Victrelis-treated patients who responded well after the lead-in PR therapy period achieved SVR rates of 79%. The SVR for patients treated using only PR was 25%. Among patients with poor response after the four-week lead-in, the SVR rate was 34% for those receiving PR plus Victrelis, and 0% for those continuing on just PR therapy.
A prespecified analysis of the Phase III trials in addition showed that IL28B status was also a strong baseline predictor of viral response among Victrelis-treated patients. The data, also presented at EASL, showed that among patients carrying the CC gene allele, 89% of treatment-naive patients and 82% of previously treatment-failure patients had an early response defined as undetectable virus at treatment week eight and were eligible for shorter duration of therapy. Among patients carrying the ‘less favorable’ CT or TT alleles, the early response rates were 52% for the treatment-naive cohort and 48% for the treatment-failure patients.
Primary results from the NEJM-published Respond-2 and Sprint-2 studies showed that among patients who had previously failed treatment, the 48-week SVR rate was 66% for those treated using Victrelis plus PR compared with 21% for patients treated using PR and placebo. Among treatment naive patients the SVR rate was 66% for patients receiving Victrelis plus PR and 38% for the PR therapy cohort.
“Based on new analyses of these studies, identification of a patient’s IL28B status prior to treatment, used in conjunction with a patient’s response after the four-week lead-in period, provided information on the likelihood of achieving SVR when Victrelis was added to standard therapy,” concludes Fred Poordad, M.D., chief of hepatology and liver transplantation at Cedars-Sinai Medical Center in Los Angeles, and lead author of the HCV Sprint-2 study.
Source
New analyses of Phase III trial data suggests that identifying HCV patients’ IL28B status and evaluating their initial response to peginterferon alfa-2b and ribavirin (PR) therapy can help predict those who will achieve a sustained virologic response (SVR) when Merck & Co.’s oral protease inhibitor candidate Victrelis® (boceprivir) is subsequently added to the treatment mix.
The new analyses, presented at the International Liver Congress/46th European Association for the Study of Liver (EASL) annual meeting, coincided with publication in The New England Journal of Medicine of data from the Phase III HCV Respond-2 and HCV Sprint-2 studies evaluating Vectrelis combined with PR in patients who had failed prior PR therapy and who were new to treatment, respectively. Both trials formed part of the regulatory submissions for Victrelis, which were accepted for accelerated review by both FDA and the EMA in January.
The new data presented at EASL emerged from additional analyses of both the Respond-2 and Sprint-2 studies. In the Sprint-2 treatment-naïve study, patients receiving Victrelis who had good response to PR therapy after the four-week lead-in period achieved SVR rates of 79% over the 48-week treatment period. The SVR rate for patients in the PR therapy control arm who initially responded well to PR therapy was 51%. Among patients with poor response after the four-week lead-in, the SVR rate was 38% for Vicrelis-treated patients in the 48-week treatment arm compared with an SVR rate of 4% in the PR control arm.
In the Respond-2 treatment-failure study, Victrelis-treated patients who responded well after the lead-in PR therapy period achieved SVR rates of 79%. The SVR for patients treated using only PR was 25%. Among patients with poor response after the four-week lead-in, the SVR rate was 34% for those receiving PR plus Victrelis, and 0% for those continuing on just PR therapy.
A prespecified analysis of the Phase III trials in addition showed that IL28B status was also a strong baseline predictor of viral response among Victrelis-treated patients. The data, also presented at EASL, showed that among patients carrying the CC gene allele, 89% of treatment-naive patients and 82% of previously treatment-failure patients had an early response defined as undetectable virus at treatment week eight and were eligible for shorter duration of therapy. Among patients carrying the ‘less favorable’ CT or TT alleles, the early response rates were 52% for the treatment-naive cohort and 48% for the treatment-failure patients.
Primary results from the NEJM-published Respond-2 and Sprint-2 studies showed that among patients who had previously failed treatment, the 48-week SVR rate was 66% for those treated using Victrelis plus PR compared with 21% for patients treated using PR and placebo. Among treatment naive patients the SVR rate was 66% for patients receiving Victrelis plus PR and 38% for the PR therapy cohort.
“Based on new analyses of these studies, identification of a patient’s IL28B status prior to treatment, used in conjunction with a patient’s response after the four-week lead-in period, provided information on the likelihood of achieving SVR when Victrelis was added to standard therapy,” concludes Fred Poordad, M.D., chief of hepatology and liver transplantation at Cedars-Sinai Medical Center in Los Angeles, and lead author of the HCV Sprint-2 study.
Source
Boceprevir Effective for Hepatitis C Virus Infection
Laurie Barclay, MD
March 31, 2011 — Boceprevir is effective in the treatment of previously treated and untreated patients with hepatitis C virus (HCV) infection, according to the results of 2 randomized trials reported in the March 30 issue of the New England Journal of Medicine.
RESPOND-2 Trial
"In patients with chronic infection with [HCV] genotype 1 who do not have a sustained response to therapy with peginterferon–ribavirin, outcomes after retreatment are suboptimal," write Bruce R. Bacon, MD, from Saint Louis University School of Medicine in Missouri, and colleagues from the HCV Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 (RESPOND-2) investigators. "Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3...active site, has been suggested as an additional treatment."
The study goal was to examine the effect of boceprevir added to peginterferon–ribavirin for retreatment of patients with chronic HCV genotype 1 infection. During the lead-in period, the 403 participants all received peginterferon alfa-2b and ribavirin for 4 weeks. Using a 1:2:2 ratio, participants were randomly assigned to group 1 (control group) receiving placebo plus peginterferon–ribavirin for 44 weeks, group 2, or group 3. Participants in group 2 received boceprevir plus peginterferon–ribavirin for 32 weeks, and patients in whom the HCV RNA level was detectable at week 8 received placebo plus peginterferon–ribavirin for 12 more weeks. In group 3, participants received boceprevir plus peginterferon–ribavirin for 44 weeks.
Compared with the control group, the 2 boceprevir groups had a significantly higher rate of sustained virologic response (group 2, 59%; group 3, 66%; control group, 21%; P < .001). Among participants with an undetectable HCV RNA level at week 8, sustained virologic response rate was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients in whom HCV RNA level decreased by less than 1 log10 IU/mL at treatment week 4, rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively.
The boceprevir groups had higher frequencies of anemia than the control group, resulting in administration of erythropoietin in 41% to 46% of boceprevir-treated patients compared with 21% of the control patients.
"The addition of boceprevir to peginterferon–ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon–ribavirin alone," the study authors write.
SPRINT-2 Trial
The second study, a double-blind trial by Fred Poordad, MD, from Cedars-Sinai Medical Center in Los Angeles, California, and colleagues from the Serine Protease Inhibitor Therapy 2 (SPRINT-2) investigators, had a study design similar to that of the RESPOND-2 study except that participants were previously untreated adults with HCV genotype 1 infection. Nonblack patients (n = 938) and black patients (n = 159) were enrolled and analyzed separately.
Sustained virologic response in the nonblack cohort occurred in 40% (125/311) of the patients in group 1, 67% (211/316) of the patients in group 2 (P < .001), and 68% (213/311) of the patients in group 3 (P < .001). For the black cohort, the corresponding rates were 23% (12/52 patients), 42% (22/52 patients; P = .04), and 53% (29/55 patients; P = .004), respectively.
Forty-four percent of patients in group 2 received peginterferon–ribavirin for 28 weeks. Dose reductions caused by anemia occurred in 13% of control patients and 21% of patients receiving boceprevir, and discontinuations caused by anemia in occurred in 1% and 2% of control patients and patients receiving boceprevir, respectively.
"The addition of boceprevir to standard therapy with peginterferon–ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection," the study authors write. "The rates were similar with 24 weeks and 44 weeks of boceprevir."
Limitations of this study include relatively small numbers of patients with cirrhosis and relatively small numbers of black patients in whom the HCV RNA level was detectable between weeks 8 and 24, warranting further study to define optimal therapy in these populations.
New Era of HCV Therapy
In an accompanying editorial, Donald M. Jensen, MD, from the Center for Liver Diseases, University of Chicago Medical Center in Illinois, discusses the beginning of a new era of HCV therapy. He noted that adverse effects associated with boceprevir treatment included anemia, rash, dry skin, and dysgeusia. However, only 8% to 12% of patients discontinued boceprevir because of these adverse events.
"HCV protease inhibitors represent a major advance in our ability to treat chronic HCV infection," Dr. Jensen writes. "Future therapy will be more complex, not easier, but the improvement in the rate of sustained virologic response with boceprevir, to nearly 70% in the SPRINT-2 trial and to more than twice the rate in previously treated patients in HCV RESPOND-2, have been eagerly awaited. We will soon embark on a new era of successful HCV therapy."
Schering-Plough (now Merck) supported both studies. Disclosure forms provided by the study authors and editorialists are available with the full text of these articles at NEJM.org.
N Engl J Med. 2011;364:1207-1217, 1195-1206, 1272-1274.
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
Source
March 31, 2011 — Boceprevir is effective in the treatment of previously treated and untreated patients with hepatitis C virus (HCV) infection, according to the results of 2 randomized trials reported in the March 30 issue of the New England Journal of Medicine.
RESPOND-2 Trial
"In patients with chronic infection with [HCV] genotype 1 who do not have a sustained response to therapy with peginterferon–ribavirin, outcomes after retreatment are suboptimal," write Bruce R. Bacon, MD, from Saint Louis University School of Medicine in Missouri, and colleagues from the HCV Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 (RESPOND-2) investigators. "Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3...active site, has been suggested as an additional treatment."
The study goal was to examine the effect of boceprevir added to peginterferon–ribavirin for retreatment of patients with chronic HCV genotype 1 infection. During the lead-in period, the 403 participants all received peginterferon alfa-2b and ribavirin for 4 weeks. Using a 1:2:2 ratio, participants were randomly assigned to group 1 (control group) receiving placebo plus peginterferon–ribavirin for 44 weeks, group 2, or group 3. Participants in group 2 received boceprevir plus peginterferon–ribavirin for 32 weeks, and patients in whom the HCV RNA level was detectable at week 8 received placebo plus peginterferon–ribavirin for 12 more weeks. In group 3, participants received boceprevir plus peginterferon–ribavirin for 44 weeks.
Compared with the control group, the 2 boceprevir groups had a significantly higher rate of sustained virologic response (group 2, 59%; group 3, 66%; control group, 21%; P < .001). Among participants with an undetectable HCV RNA level at week 8, sustained virologic response rate was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients in whom HCV RNA level decreased by less than 1 log10 IU/mL at treatment week 4, rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively.
The boceprevir groups had higher frequencies of anemia than the control group, resulting in administration of erythropoietin in 41% to 46% of boceprevir-treated patients compared with 21% of the control patients.
"The addition of boceprevir to peginterferon–ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon–ribavirin alone," the study authors write.
SPRINT-2 Trial
The second study, a double-blind trial by Fred Poordad, MD, from Cedars-Sinai Medical Center in Los Angeles, California, and colleagues from the Serine Protease Inhibitor Therapy 2 (SPRINT-2) investigators, had a study design similar to that of the RESPOND-2 study except that participants were previously untreated adults with HCV genotype 1 infection. Nonblack patients (n = 938) and black patients (n = 159) were enrolled and analyzed separately.
Sustained virologic response in the nonblack cohort occurred in 40% (125/311) of the patients in group 1, 67% (211/316) of the patients in group 2 (P < .001), and 68% (213/311) of the patients in group 3 (P < .001). For the black cohort, the corresponding rates were 23% (12/52 patients), 42% (22/52 patients; P = .04), and 53% (29/55 patients; P = .004), respectively.
Forty-four percent of patients in group 2 received peginterferon–ribavirin for 28 weeks. Dose reductions caused by anemia occurred in 13% of control patients and 21% of patients receiving boceprevir, and discontinuations caused by anemia in occurred in 1% and 2% of control patients and patients receiving boceprevir, respectively.
"The addition of boceprevir to standard therapy with peginterferon–ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection," the study authors write. "The rates were similar with 24 weeks and 44 weeks of boceprevir."
Limitations of this study include relatively small numbers of patients with cirrhosis and relatively small numbers of black patients in whom the HCV RNA level was detectable between weeks 8 and 24, warranting further study to define optimal therapy in these populations.
New Era of HCV Therapy
In an accompanying editorial, Donald M. Jensen, MD, from the Center for Liver Diseases, University of Chicago Medical Center in Illinois, discusses the beginning of a new era of HCV therapy. He noted that adverse effects associated with boceprevir treatment included anemia, rash, dry skin, and dysgeusia. However, only 8% to 12% of patients discontinued boceprevir because of these adverse events.
"HCV protease inhibitors represent a major advance in our ability to treat chronic HCV infection," Dr. Jensen writes. "Future therapy will be more complex, not easier, but the improvement in the rate of sustained virologic response with boceprevir, to nearly 70% in the SPRINT-2 trial and to more than twice the rate in previously treated patients in HCV RESPOND-2, have been eagerly awaited. We will soon embark on a new era of successful HCV therapy."
Schering-Plough (now Merck) supported both studies. Disclosure forms provided by the study authors and editorialists are available with the full text of these articles at NEJM.org.
N Engl J Med. 2011;364:1207-1217, 1195-1206, 1272-1274.
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
Source
Inhibition of HCV 3a core gene through Silymarin and its Fractions
Published on: 2011-04-01
Hepatitis C is a major health problem affecting 270 million individuals in world including Pakistan. Current treatment regimen, interferon alpha and ribavirin only cure half of patients due to side effects and high cost.
Results: In the present study Silybum marianum (Milk thistle) seeds were collected, extracted and analyzed against HCV 3a core gene by transiently transfecting the liver cells with HCV core plasmid.
Our results demonstrated that Silymarin (SM) dose dependently inhibit the expression or function of HCV core gene at a non toxic concentration while the GAPDH remained constant. To identify the active ingredient, SM was fractioned by thin layer chromatography (TLC), column chromatography and HPLC.
Purified fractions were tested for HCV core gene and western blotting results showed that two factions of SM (S1 and S2) inhibit HCV 3a core expression or function in liver cells.
Conclusion: Our results suggest SM and its fractions (S1 and S2) inhibit HCV core gene of 3a genotype and combination of SM and its fractions with interferon will be a better option to treat HCV infection.
Author: Usman AshfaqTariq JavedSidra RehmanZafar NawazSheikh Riazuddin
Credits/Source: Virology Journal 2011, 8:153
Source
Hepatitis C is a major health problem affecting 270 million individuals in world including Pakistan. Current treatment regimen, interferon alpha and ribavirin only cure half of patients due to side effects and high cost.
Results: In the present study Silybum marianum (Milk thistle) seeds were collected, extracted and analyzed against HCV 3a core gene by transiently transfecting the liver cells with HCV core plasmid.
Our results demonstrated that Silymarin (SM) dose dependently inhibit the expression or function of HCV core gene at a non toxic concentration while the GAPDH remained constant. To identify the active ingredient, SM was fractioned by thin layer chromatography (TLC), column chromatography and HPLC.
Purified fractions were tested for HCV core gene and western blotting results showed that two factions of SM (S1 and S2) inhibit HCV 3a core expression or function in liver cells.
Conclusion: Our results suggest SM and its fractions (S1 and S2) inhibit HCV core gene of 3a genotype and combination of SM and its fractions with interferon will be a better option to treat HCV infection.
Author: Usman AshfaqTariq JavedSidra RehmanZafar NawazSheikh Riazuddin
Credits/Source: Virology Journal 2011, 8:153
Source
Cirrhosis and HCC Have Risen Dramatically in Hepatitis C Patients
By: MARY ANN MOON, Internal Medicine News Digital Network
04/01/11
The burden of cirrhosis, hepatic decompensation, and hepatocellular carcinoma has risen dramatically during the past decade among patients with chronic hepatitis C virus infection, Dr. Fasiha Kanwal and her colleagues reported in the April issue of Gastroenterology.
In a large retrospective cohort study of more than 300,000 patients at Department of Veterans Affairs medical centers across the country, the prevalence of cirrhosis and hepatic decompensation doubled – and that of hepatocellular carcinoma increased 19-fold – between 1996 and 2006.
"Thus, 1 of 5 patients with HCV had cirrhosis and 1 of 100 patients with HCV had hepatocellular carcinoma in the 2006 calendar year," said Dr. Kanwal of the John Cochran division of the St. Louis VA Medical Center, and her associates.
This increase was significantly greater than that predicted by several mathematical models, they noted.
The investigators examined the burden of HCV illness directly, quantifying changes in the prevalence of cirrhosis and assessing trends in its related complications, because indirect data had suggested that it was increasing. "Our data are the first to provide direct and contemporary estimates of the time trends in the burden of cirrhosis from the largest assembled group of HCV patients anywhere in the world," the researchers said.
"Measuring the burden in HCV is important ... to understand changes in the pattern of care delivery, provide a critical insight into the magnitude of the problem, and guide both clinicians and the health care system to develop strategies [for] providing timely and effective care to this highly vulnerable group of patients," they said.
They analyzed data from the VA’s HCV database, which included HCV patients who sought treatment at any of 128 VA medical centers in 1996-2006. There were 17,261 patients in the database in 1996, a total that increased to 106,242 in 2006.
Overall, the number of patients with HCV who had cirrhosis rose from 2,061 to 23,294 during the study period, the number with hepatic decompensation rose from 1,012 to 13,724, and the number with hepatocellular carcinoma rose from 17 to 1,619.
The prevalence of cirrhosis doubled from 9% to 18.5% during that time, and still continues to rise. The prevalence of hepatic decompensation rose in parallel, with a twofold increase (from 5% to 11%).
The prevalence of hepatocellular carcinoma also rose, but the upward slope became particularly steep from 2003 onward. Prevalence grew 19-fold (from 0.07% to 1.3%) during the study period overall. This pattern suggests that "there might be a greater epidemic of hepatocellular carcinoma [coming] than we were expecting,’ Dr. Kanwal and her colleagues said.
Mortality of cirrhosis patients also increased over time, with a greater proportion of patients dying in recent years than in the 1990s.
The aging of the cohort explains part of these increases, but all of them persisted even after the data were adjusted to account for aging. It is not yet known what other factors play a role in these trends.
"The morbidity and mortality associated with cirrhosis and hepatocellular carcinoma may be greatly reduced if potentially life-saving interventions – such as liver transplantation and, for HCC, local ablation and surgical resection – are applied in a timely manner," they noted.
However, recent data from other studies demonstrate that patients with cirrhosis rarely receive high-quality health care, and their own previous research found that "the quality of health care given to patients with HCV infection falls far short of that recommended by practice guidelines."
In this study, only 16% of the cohort had ever received a prescription for interferon.
"Given the significant increase in the number of patients with cirrhosis, and given the data suggesting marked gaps in the quality of care, the health care system may need to rechannel its efforts in patients with HCV to provide timely and effective care to the patients with cirrhosis," the investigators said.
The research was supported in part by grants from the Department of Veterans Affairs. The authors had nothing to disclose.
Source
04/01/11
The burden of cirrhosis, hepatic decompensation, and hepatocellular carcinoma has risen dramatically during the past decade among patients with chronic hepatitis C virus infection, Dr. Fasiha Kanwal and her colleagues reported in the April issue of Gastroenterology.
In a large retrospective cohort study of more than 300,000 patients at Department of Veterans Affairs medical centers across the country, the prevalence of cirrhosis and hepatic decompensation doubled – and that of hepatocellular carcinoma increased 19-fold – between 1996 and 2006.
"Thus, 1 of 5 patients with HCV had cirrhosis and 1 of 100 patients with HCV had hepatocellular carcinoma in the 2006 calendar year," said Dr. Kanwal of the John Cochran division of the St. Louis VA Medical Center, and her associates.
This increase was significantly greater than that predicted by several mathematical models, they noted.
The investigators examined the burden of HCV illness directly, quantifying changes in the prevalence of cirrhosis and assessing trends in its related complications, because indirect data had suggested that it was increasing. "Our data are the first to provide direct and contemporary estimates of the time trends in the burden of cirrhosis from the largest assembled group of HCV patients anywhere in the world," the researchers said.
"Measuring the burden in HCV is important ... to understand changes in the pattern of care delivery, provide a critical insight into the magnitude of the problem, and guide both clinicians and the health care system to develop strategies [for] providing timely and effective care to this highly vulnerable group of patients," they said.
They analyzed data from the VA’s HCV database, which included HCV patients who sought treatment at any of 128 VA medical centers in 1996-2006. There were 17,261 patients in the database in 1996, a total that increased to 106,242 in 2006.
Overall, the number of patients with HCV who had cirrhosis rose from 2,061 to 23,294 during the study period, the number with hepatic decompensation rose from 1,012 to 13,724, and the number with hepatocellular carcinoma rose from 17 to 1,619.
The prevalence of cirrhosis doubled from 9% to 18.5% during that time, and still continues to rise. The prevalence of hepatic decompensation rose in parallel, with a twofold increase (from 5% to 11%).
The prevalence of hepatocellular carcinoma also rose, but the upward slope became particularly steep from 2003 onward. Prevalence grew 19-fold (from 0.07% to 1.3%) during the study period overall. This pattern suggests that "there might be a greater epidemic of hepatocellular carcinoma [coming] than we were expecting,’ Dr. Kanwal and her colleagues said.
Mortality of cirrhosis patients also increased over time, with a greater proportion of patients dying in recent years than in the 1990s.
The aging of the cohort explains part of these increases, but all of them persisted even after the data were adjusted to account for aging. It is not yet known what other factors play a role in these trends.
"The morbidity and mortality associated with cirrhosis and hepatocellular carcinoma may be greatly reduced if potentially life-saving interventions – such as liver transplantation and, for HCC, local ablation and surgical resection – are applied in a timely manner," they noted.
However, recent data from other studies demonstrate that patients with cirrhosis rarely receive high-quality health care, and their own previous research found that "the quality of health care given to patients with HCV infection falls far short of that recommended by practice guidelines."
In this study, only 16% of the cohort had ever received a prescription for interferon.
"Given the significant increase in the number of patients with cirrhosis, and given the data suggesting marked gaps in the quality of care, the health care system may need to rechannel its efforts in patients with HCV to provide timely and effective care to the patients with cirrhosis," the investigators said.
The research was supported in part by grants from the Department of Veterans Affairs. The authors had nothing to disclose.
Source
EASL: Medivir: Week 24 Interim Results from TMC435 Hepatitis C Phase 2b ASPIRE Study presented at EASL
Results show potent antiviral efficacy of once daily 150 mg TMC435 in hepatitis C patients who have failed earlier treatment, especially in prior null responders, and excellent safety and tolerability
01-Apr-11 Huddinge, Sweden - Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, announces that their partner, Tibotec has presented the results of a planned Week 24 interim analysis of the phase 2b ASPIRE study for TMC435 in treatment experienced hepatitis C patients in a late-breaker session at the 46th Annual meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany.
Treatment experienced patients are known to be the most difficult to treat hepatitis C patient group.
TMC435 is a potent, once-daily, oral hepatitis C virus protease inhibitor which recently entered clinical phase 3 studies. The study enrolled patients chronically infected with genotype-1 hepatitis C virus (HCV) that had previously failed treatment with standard of care therapy (peginterferon and ribavarin). TMC435 is being jointly developed by Medivir and its partner Tibotec.
In this Week 24 interim analysis, treatment-experienced patients who failed peginterferon and ribavarin treatment achieved significantly greater virologic response rates following treatment with TMC435-containing regimen at all doses, compared with placebo. Results demonstrated that the TMC435 150 mg dose group showed the highest response, particularly in prior null responders. In this 150 mg dose group, HCV RNA levels were undetectable at week 24 for between 82% and 91% of the patients. Results also showed that there was no statistically relevant difference in safety and tolerability between the TMC435 and placebo treated groups.
Ron Long, CEO of Medivir, commented: “We are delighted that these strong results are to be presented at such a prestigious scientific conference as EASL. TMC435 continues to demonstrate why Medivir are so confident that hepatitis C treatment can be significantly changed by a more convenient, once daily protease inhibitor especially for treatment experienced patients. These data and the recent start of phase 3 clinical studies for TMC435, represent an exciting stage in Medivir’s development as a significant player in the infectious disease market.”
On-treatment response rates are shown below.
TMC12/PR48 TMC24/PR48 TMC48/PR48 TMC12/PR48 TMC24/PR48 TMC48/PR48 Pbo48/PR48
100mg 100mg 100mg 150mg 150mg 150mg
(N=66) (N=65) (N=66) (N=66) (N=68) (N=65) (N=66)
HCV RNA <25 IU/mL undetectable, % (u/N)
Overall population 67,7 (44/65) 59,4 (38/64) 53,8 (35/65) 63,1 (41/65) 70,8 (46/65) 66,2 (43/65) 1,5 (1/65)
Week 4 (RVR) *** *** *** *** *** ***
Prior null responders 33,3 (5/15) 50,0 (8/16) 25,0 (4/16) 35,3 (6/17) 41,2 (7/17) 41,2 (7/17) 0,0 (0/16)
Prior partial responders 65,2 (15/23) 40,9 (9/22) 60,9 (14/23) 65,2 (15/23) 69,6 (16/23) 68,2 (15/22) 0,0 (0/23)
Prior relapser 88,9 (24/27) 80,8 (21/26) 65,4 (17/26) 80,0 (20/25) 92,0 (23/25) 80,8 (21/26) 3,8 (1/26)
Overall population 87,1 (54/62) 84,5 (49/58) 85,2 (52/61) 85,7 (54/63) 90,8 (59/65) 90,3 (56/62) 51,9 (28/54)
Week 24 *** *** *** *** *** ***
Prior null responders 71,4 (10/14) 83,3 (10/12) 68,8 (11/16) 70,6 (12/17) 81,3 (13/16) 93,3 (14/15) 44,4 (4/9)
Prior partial responders 86,6 (19/22) 80,0 (16/20) 85,7 (18/21) 86,4 (19/22) 90,9 (20/22) 86,4 (19/22) 19,0 (4/21)
Prior relapser 96,2 (25/26) 88,5 (23/26) 95,8 (23/24) 95,8 (23/24) 96,3 (26/27) 92,0 (23/25) 83,3 (20/24)
*** Statistically significant difference versus placebo, p<0,0
The ASPIRE study evaluates the effect of TMC435 in combination with standard of care (SoC) in 462 patients infected with the difficult to treat genotype-1 hepatitis C virus who had undergone and failed prior treatment with (SoC). The study includes patients that have relapsed, achieved partial response, or achieved no response (null responders) to treatment with standard of care. TMC435 was administered once daily at a dose of either 100 mg or 150mg given for either 12, 24, or 48 weeks in combination with standard of care. Standard of care treatment was continued until the study completion at week 48.
As well as the late-breaker ASPIRE data presented, a further three presentations will be made at EASL on TMC435. These include:
Oral presentation: Impact of IL28b genotype and pretreatment serum IP-10 in treatment-naïve genotype-1 HCV patients treated with TMC435 in combination with peginterferonα-2a and ribavirin in PILLAR study, J. Aerssens, which found that during 24 weeks of treatment, IL28B genotype and serum IP-10 were predictive of response in patients receiving standard of care (peginterferon and ribavirin) but had limited predictive value in patients treated with both TMC435 and peginterferon and ribavirin, therefore suggesting that TMC435, a potent, once daily oral protease inhibitor, may overcome the negative consequences of unfavourable host genotype encountered with pegIFN/RBV.
Poster presentation No.472: Pharmacokinetics of TMC435 in subjects with moderate hepatic impairment, V. Sekar, which found that no TMC435 dose adjustment was necessary for patients with moderate liver impairment.
Poster presentation No.1221: Treatment outcome and resistance analysis in HCV genotype 1 patients previously exposed to TMC435 monotherapy and re-treated with TMC435 in combination with pegifnα‑2a/ribavirin, O. Lenz, which found that viral variants in patients who had received TMC435 as a monotherapy were no longer detected over time and successful treatment after prior exposure to TMC435 with emergence of resistance variants was possible in 3/5 patients who had failed interferon-based therapy.
About TMC435 in other clinical studies
TMC435 is a once-daily (q.d.) protease inhibitor drug jointly developed by Medivir and Tibotec Pharmaceuticals, to treat chronic hepatitis C virus infections.
Three clinical phase 3 response guided studies were recently initiated:
· TMC435-C208 or QUEST-1 includes approximately 375 treatment-naïve patients
· TMC435-C216 or QUEST-2 includes approximately 375 treatment-naïve patients
· TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
In parallel to the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naïve and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
A phase 3 program for TMC435 has also recently been launched in Japan.
For additional information for these studies, please see http://www.clinicaltrials.gov/
For more information about Medivir, please contact:
Medivir (http://www.medivir.com/ (http://www.medivir.com/)):
Rein Piir, CFO & VP Investor Relations Mobile: +46 708 537 292
Bertil Samuelsson, CFO Mobile: +46 (70) 576 13 50
M:Communications: Mary-Jane Elliott / Amber Bielecka / Katja Toon Medivir@mcomgroup.com (Medivir@mcomgroup.com) +44(0)20 7920 2330
USA: Roland Tomforde +1 212-232-2356
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is TMC435, a protease inhibitor which has recently entered phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
Medivir is also marketing its first product, the unique cold sore product Xerese™/Xerclear® which has recently been launched on the US market. Xerese™/Xerclear®, which is also approved in Europe, is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia and with Meda AB in North America, Canada and Mexico. Medivir has retained the Rx rights for Xerclear® in Sweden and Finland.
For more information about Medivir, please visit the Company’s website: www.medivir.com (http://www.medivir.com/).
Source
01-Apr-11 Huddinge, Sweden - Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, announces that their partner, Tibotec has presented the results of a planned Week 24 interim analysis of the phase 2b ASPIRE study for TMC435 in treatment experienced hepatitis C patients in a late-breaker session at the 46th Annual meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany.
Treatment experienced patients are known to be the most difficult to treat hepatitis C patient group.
TMC435 is a potent, once-daily, oral hepatitis C virus protease inhibitor which recently entered clinical phase 3 studies. The study enrolled patients chronically infected with genotype-1 hepatitis C virus (HCV) that had previously failed treatment with standard of care therapy (peginterferon and ribavarin). TMC435 is being jointly developed by Medivir and its partner Tibotec.
In this Week 24 interim analysis, treatment-experienced patients who failed peginterferon and ribavarin treatment achieved significantly greater virologic response rates following treatment with TMC435-containing regimen at all doses, compared with placebo. Results demonstrated that the TMC435 150 mg dose group showed the highest response, particularly in prior null responders. In this 150 mg dose group, HCV RNA levels were undetectable at week 24 for between 82% and 91% of the patients. Results also showed that there was no statistically relevant difference in safety and tolerability between the TMC435 and placebo treated groups.
Ron Long, CEO of Medivir, commented: “We are delighted that these strong results are to be presented at such a prestigious scientific conference as EASL. TMC435 continues to demonstrate why Medivir are so confident that hepatitis C treatment can be significantly changed by a more convenient, once daily protease inhibitor especially for treatment experienced patients. These data and the recent start of phase 3 clinical studies for TMC435, represent an exciting stage in Medivir’s development as a significant player in the infectious disease market.”
On-treatment response rates are shown below.
TMC12/PR48 TMC24/PR48 TMC48/PR48 TMC12/PR48 TMC24/PR48 TMC48/PR48 Pbo48/PR48
100mg 100mg 100mg 150mg 150mg 150mg
(N=66) (N=65) (N=66) (N=66) (N=68) (N=65) (N=66)
HCV RNA <25 IU/mL undetectable, % (u/N)
Overall population 67,7 (44/65) 59,4 (38/64) 53,8 (35/65) 63,1 (41/65) 70,8 (46/65) 66,2 (43/65) 1,5 (1/65)
Week 4 (RVR) *** *** *** *** *** ***
Prior null responders 33,3 (5/15) 50,0 (8/16) 25,0 (4/16) 35,3 (6/17) 41,2 (7/17) 41,2 (7/17) 0,0 (0/16)
Prior partial responders 65,2 (15/23) 40,9 (9/22) 60,9 (14/23) 65,2 (15/23) 69,6 (16/23) 68,2 (15/22) 0,0 (0/23)
Prior relapser 88,9 (24/27) 80,8 (21/26) 65,4 (17/26) 80,0 (20/25) 92,0 (23/25) 80,8 (21/26) 3,8 (1/26)
Overall population 87,1 (54/62) 84,5 (49/58) 85,2 (52/61) 85,7 (54/63) 90,8 (59/65) 90,3 (56/62) 51,9 (28/54)
Week 24 *** *** *** *** *** ***
Prior null responders 71,4 (10/14) 83,3 (10/12) 68,8 (11/16) 70,6 (12/17) 81,3 (13/16) 93,3 (14/15) 44,4 (4/9)
Prior partial responders 86,6 (19/22) 80,0 (16/20) 85,7 (18/21) 86,4 (19/22) 90,9 (20/22) 86,4 (19/22) 19,0 (4/21)
Prior relapser 96,2 (25/26) 88,5 (23/26) 95,8 (23/24) 95,8 (23/24) 96,3 (26/27) 92,0 (23/25) 83,3 (20/24)
*** Statistically significant difference versus placebo, p<0,0
The ASPIRE study evaluates the effect of TMC435 in combination with standard of care (SoC) in 462 patients infected with the difficult to treat genotype-1 hepatitis C virus who had undergone and failed prior treatment with (SoC). The study includes patients that have relapsed, achieved partial response, or achieved no response (null responders) to treatment with standard of care. TMC435 was administered once daily at a dose of either 100 mg or 150mg given for either 12, 24, or 48 weeks in combination with standard of care. Standard of care treatment was continued until the study completion at week 48.
As well as the late-breaker ASPIRE data presented, a further three presentations will be made at EASL on TMC435. These include:
Oral presentation: Impact of IL28b genotype and pretreatment serum IP-10 in treatment-naïve genotype-1 HCV patients treated with TMC435 in combination with peginterferonα-2a and ribavirin in PILLAR study, J. Aerssens, which found that during 24 weeks of treatment, IL28B genotype and serum IP-10 were predictive of response in patients receiving standard of care (peginterferon and ribavirin) but had limited predictive value in patients treated with both TMC435 and peginterferon and ribavirin, therefore suggesting that TMC435, a potent, once daily oral protease inhibitor, may overcome the negative consequences of unfavourable host genotype encountered with pegIFN/RBV.
Poster presentation No.472: Pharmacokinetics of TMC435 in subjects with moderate hepatic impairment, V. Sekar, which found that no TMC435 dose adjustment was necessary for patients with moderate liver impairment.
Poster presentation No.1221: Treatment outcome and resistance analysis in HCV genotype 1 patients previously exposed to TMC435 monotherapy and re-treated with TMC435 in combination with pegifnα‑2a/ribavirin, O. Lenz, which found that viral variants in patients who had received TMC435 as a monotherapy were no longer detected over time and successful treatment after prior exposure to TMC435 with emergence of resistance variants was possible in 3/5 patients who had failed interferon-based therapy.
About TMC435 in other clinical studies
TMC435 is a once-daily (q.d.) protease inhibitor drug jointly developed by Medivir and Tibotec Pharmaceuticals, to treat chronic hepatitis C virus infections.
Three clinical phase 3 response guided studies were recently initiated:
· TMC435-C208 or QUEST-1 includes approximately 375 treatment-naïve patients
· TMC435-C216 or QUEST-2 includes approximately 375 treatment-naïve patients
· TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
In parallel to the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naïve and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
A phase 3 program for TMC435 has also recently been launched in Japan.
For additional information for these studies, please see http://www.clinicaltrials.gov/
For more information about Medivir, please contact:
Medivir (http://www.medivir.com/ (http://www.medivir.com/)):
Rein Piir, CFO & VP Investor Relations Mobile: +46 708 537 292
Bertil Samuelsson, CFO Mobile: +46 (70) 576 13 50
M:Communications: Mary-Jane Elliott / Amber Bielecka / Katja Toon Medivir@mcomgroup.com (Medivir@mcomgroup.com) +44(0)20 7920 2330
USA: Roland Tomforde +1 212-232-2356
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is TMC435, a protease inhibitor which has recently entered phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
Medivir is also marketing its first product, the unique cold sore product Xerese™/Xerclear® which has recently been launched on the US market. Xerese™/Xerclear®, which is also approved in Europe, is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia and with Meda AB in North America, Canada and Mexico. Medivir has retained the Rx rights for Xerclear® in Sweden and Finland.
For more information about Medivir, please visit the Company’s website: www.medivir.com (http://www.medivir.com/).
Source
EASL: Importance of policy action to help reduce HCV-related deaths across Europe by 2025
Public release date: 31-Mar-2011
Contact: Isabelle Scali
easlpressoffice@cohnwolfe.com
44-771-743-5103
European Association for the Study of the Liver
Current health inequalities could limit results
New findings from two modeling studies presented at the International Liver Congress support the call to action from medical experts and patients in relation to the challenge health inequalities represent in the diagnosis and access to HCV treatment.
The first modelling study looks at current treatment practices and available epidemiological data across a number of EU countries (including Belgium, France, Germany, Italy, Spain and the UK), and shows that based on current practice HCV-related morbidity and mortality (linked to liver cancer deaths) will be reduced by 10% over nine years (2012 – 2021). In addition, the incidence of cirrhosis will also be reduced by 16%. Both results take into consideration variations across countries in screening, diagnosis and treatment standards.
The study also considered HCV progression if 70% of treatment naive patients and all non-responders and relapsers were treated with a protease inhibitor from 2012 onwards (increasing average SVR to 70% and 60.5% in non-responders and treatment-naive genotype 1 patients respectively). Based on this scenario, findings show that the overall HCV-related mortality would decrease by a further 12% over the same period, corresponding to a relative impact of 117% compared to current practice.
Based on these forecasts, experts conclude that the development and implementation of ambitious policy strategies to ensure effective access to diagnosis and treatment alongside the availability of new therapies (such as proteases inhibitors) could have a major impact in further reducing HCV-related mortality in the future.
A second modelling study looked at French health resource allocation and how this may change with the introduction of triple therapy for non-responders in the near future. In France, the data show the number of patients eligible for treatment (treatment-naive and previous non-responders) will increase two to three folds, which equates to an additional 9,900 to 14,300 patients by 2012.
This demonstrates the need to adjust allocation of health resources at national level to meet this demand.
Mark Thursz, EASL's Vice-Secretary commented: "These types of modelling studies are useful in providing us with data to support our policy efforts with political audiences. We have been saying, alongside patients, that the current challenges to managing viral hepatitis effectively are linked to a wide discrepancy in diagnosis and treatment standards across the different Member States. Now we can build a stronger case when discussing the development of effective health strategies within the EU and at Member State level. The good news is that antiviral treatments are being proven to be effective in substantially reducing HCV-related mortality in Europe. We must strengthen our efforts towards a better identification of carriers needing management and treatment."
HCV is a major cause of acute hepatitis and chronic liver disease. Globally, an estimated 130� million people are chronically infected with HCV and 3 million are newly infected each year.
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. Deuffic-Burban S et al. HCV burden in Europe: Impact of national treatment practices on future HCV-related morbidity and mortality through a modelling approach. Abstract presented at the International Liver CongressTM 2011
2. Deuffic-Burban S et al. The availability of direct acting antivirals in 2012: A French model-based analysis of the increased number of patients treated for chronic HCV infection. Abstract presented at the International Liver CongressTM 2011
3. WHO Europe. Hepatitis C facts and figures. http://www.euro.who.int/en/what-we-do/health-topics/diseases-and-conditions/hepatitis/facts-and-figures/hepatitis-c. Accessed 08 March 2011
Source
Contact: Isabelle Scali
easlpressoffice@cohnwolfe.com
44-771-743-5103
European Association for the Study of the Liver
Current health inequalities could limit results
New findings from two modeling studies presented at the International Liver Congress support the call to action from medical experts and patients in relation to the challenge health inequalities represent in the diagnosis and access to HCV treatment.
The first modelling study looks at current treatment practices and available epidemiological data across a number of EU countries (including Belgium, France, Germany, Italy, Spain and the UK), and shows that based on current practice HCV-related morbidity and mortality (linked to liver cancer deaths) will be reduced by 10% over nine years (2012 – 2021). In addition, the incidence of cirrhosis will also be reduced by 16%. Both results take into consideration variations across countries in screening, diagnosis and treatment standards.
The study also considered HCV progression if 70% of treatment naive patients and all non-responders and relapsers were treated with a protease inhibitor from 2012 onwards (increasing average SVR to 70% and 60.5% in non-responders and treatment-naive genotype 1 patients respectively). Based on this scenario, findings show that the overall HCV-related mortality would decrease by a further 12% over the same period, corresponding to a relative impact of 117% compared to current practice.
Based on these forecasts, experts conclude that the development and implementation of ambitious policy strategies to ensure effective access to diagnosis and treatment alongside the availability of new therapies (such as proteases inhibitors) could have a major impact in further reducing HCV-related mortality in the future.
A second modelling study looked at French health resource allocation and how this may change with the introduction of triple therapy for non-responders in the near future. In France, the data show the number of patients eligible for treatment (treatment-naive and previous non-responders) will increase two to three folds, which equates to an additional 9,900 to 14,300 patients by 2012.
This demonstrates the need to adjust allocation of health resources at national level to meet this demand.
Mark Thursz, EASL's Vice-Secretary commented: "These types of modelling studies are useful in providing us with data to support our policy efforts with political audiences. We have been saying, alongside patients, that the current challenges to managing viral hepatitis effectively are linked to a wide discrepancy in diagnosis and treatment standards across the different Member States. Now we can build a stronger case when discussing the development of effective health strategies within the EU and at Member State level. The good news is that antiviral treatments are being proven to be effective in substantially reducing HCV-related mortality in Europe. We must strengthen our efforts towards a better identification of carriers needing management and treatment."
HCV is a major cause of acute hepatitis and chronic liver disease. Globally, an estimated 130� million people are chronically infected with HCV and 3 million are newly infected each year.
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. Deuffic-Burban S et al. HCV burden in Europe: Impact of national treatment practices on future HCV-related morbidity and mortality through a modelling approach. Abstract presented at the International Liver CongressTM 2011
2. Deuffic-Burban S et al. The availability of direct acting antivirals in 2012: A French model-based analysis of the increased number of patients treated for chronic HCV infection. Abstract presented at the International Liver CongressTM 2011
3. WHO Europe. Hepatitis C facts and figures. http://www.euro.who.int/en/what-we-do/health-topics/diseases-and-conditions/hepatitis/facts-and-figures/hepatitis-c. Accessed 08 March 2011
Source
EASL: Conatus Pharmaceuticals Presents Results From a Phase 2 Clinical Trial of CTS-1027 in HCV Genotype 1 Null-Responders
SAN DIEGO, March 31, 2011 /PRNewswire/ -- Conatus Pharmaceuticals Inc. announced today 24-week interim results from a clinical trial with CTS-1027 in combination with Peginterferon Alpha-2a (Pegasys®) and ribavirin (Copegus®) in a treatment experienced, hepatitis C virus (HCV) null-responder patient population. Null-responder patients are the most difficult to treat patient population and are clinically defined as those patients failing to achieve an early virologic response (EVR) when undergoing treatment with the current standard of care (SOC; pegylated interferon and ribavirin). EVR is defined as at least a 2 log decline in HCV-RNA by week 12 of SOC treatment. The CTS-1027-04 clinical trial enrolled 67 HCV genotype 1 null-responder patients. The clinical trial is a single arm and open label design with sustained viral response (SVR; no detectable virus 24 weeks after the end of treatment) as its primary end point. At week 12, 51% (31/61) of patients receiving 15 mg twice a day of CTS-1027 in addition to standard doses of Pegasys® and Copegus® achieved an EVR on a per protocol (PP) basis. HCV-RNA was below quantifiable limit (BQL) in 5 patients (8.2%, PP) at week 12 and increased to 17 patients (34%, 17/50, PP) at week 24. This clinical trial is ongoing and final SVR results are expected in 2011.
Data from the CTS-1027-04 clinical trial were presented at the 46th annual meeting of the European Association for the Study of the Liver (EASL) held in Berlin, Germany, as Abstract 468. The full abstract is available at http://www.conatuspharma.com/.
Consistent with expectations, the majority of patients tested for genetic analysis of IL-28B (95%, 58/61) carried the CT or TT allelic variant. Patients possessing these genetic variants are predicted to be less responsive to the antiviral actions of interferon.
"Most other approaches to treat HCV infection are direct-acting anti-viral drugs whose activity is directed against virus proteins or enzymes with the objective of reducing the production of virus in infected cells. CTS-1027, by comparison, is distinctly different in that its activity is hypothesized to facilitate the immune clearance of virus-infected cells and decrease the frequency of new infections, both of which are of key importance in curing HCV infections," said Alfred P. Spada, Ph.D., Senior Vice President of R & D of Conatus.
"Clearance of infected cells is a slow but essential process to achieving a sustained viral response. It is intriguing to observe this significant improvement in viral load reduction at such a low dose of CTS-1027. A recently initiated Phase 2b clinical trial (CTS-1027-05) will test CTS-1027 at higher doses in combination with Pegasys® and Copegus® in the null-responder patient population," said Steven J. Mento, Ph.D., President and CEO of Conatus.
Conatus Pharmaceuticals Inc. is a privately-held biopharmaceutical company engaged in the development of innovative human therapeutics to treat liver disease and oncology. Conatus' lead drug candidate, CTS-1027 is in multiple Phase 2 clinical trials for the treatment of hepatitis C virus (HCV). Conatus was founded by the executive management team of Idun Pharmaceuticals in July 2005 following the sale of Idun to Pfizer. For additional information, please visit http://www.conatuspharma.com/.
Pegasys® and Copegus® are registered trademarks of F. Hoffman-La Roche, Inc.
SOURCE Conatus Pharmaceuticals Inc.
RELATED LINKS
http://www.conatuspharma.com/
Source
Data from the CTS-1027-04 clinical trial were presented at the 46th annual meeting of the European Association for the Study of the Liver (EASL) held in Berlin, Germany, as Abstract 468. The full abstract is available at http://www.conatuspharma.com/.
Consistent with expectations, the majority of patients tested for genetic analysis of IL-28B (95%, 58/61) carried the CT or TT allelic variant. Patients possessing these genetic variants are predicted to be less responsive to the antiviral actions of interferon.
"Most other approaches to treat HCV infection are direct-acting anti-viral drugs whose activity is directed against virus proteins or enzymes with the objective of reducing the production of virus in infected cells. CTS-1027, by comparison, is distinctly different in that its activity is hypothesized to facilitate the immune clearance of virus-infected cells and decrease the frequency of new infections, both of which are of key importance in curing HCV infections," said Alfred P. Spada, Ph.D., Senior Vice President of R & D of Conatus.
"Clearance of infected cells is a slow but essential process to achieving a sustained viral response. It is intriguing to observe this significant improvement in viral load reduction at such a low dose of CTS-1027. A recently initiated Phase 2b clinical trial (CTS-1027-05) will test CTS-1027 at higher doses in combination with Pegasys® and Copegus® in the null-responder patient population," said Steven J. Mento, Ph.D., President and CEO of Conatus.
Conatus Pharmaceuticals Inc. is a privately-held biopharmaceutical company engaged in the development of innovative human therapeutics to treat liver disease and oncology. Conatus' lead drug candidate, CTS-1027 is in multiple Phase 2 clinical trials for the treatment of hepatitis C virus (HCV). Conatus was founded by the executive management team of Idun Pharmaceuticals in July 2005 following the sale of Idun to Pfizer. For additional information, please visit http://www.conatuspharma.com/.
Pegasys® and Copegus® are registered trademarks of F. Hoffman-La Roche, Inc.
SOURCE Conatus Pharmaceuticals Inc.
RELATED LINKS
http://www.conatuspharma.com/
Source
Transgene Announces Completion of Enrolment in HCVac (Phase II Trial) of TG4040 for the Treatment of Chronic Hepatitis C
31.03.2011 18:31
Transgene S.A. (Paris:TNG)(Euronext Paris: FR0005175080) announces that, with 154 patients randomized and treated, the enrolment of patients in the phase II HCVac trial is now complete. This study explores the combination of TG4040 (MVA-HCV) with standard of care (Pegylated-Interferon a2a and Ribavarin) in treatment naive patients with chronic genotype 1 hepatitis C.
The patients were recruited in five countries in Europe, in the United States and in Israel, and were randomized in the three arms of the study (one control arm without TG4040 and two experimental arms). HCVac investigates the efficacy and safety of two different schedules of administration of TG4040 administered in subcutaneous injections at the dose of 107 pfu in combination with the standard of care.
HCVac will measure the proportion of patients who achieve complete Early Virologic Response (cEVR), i.e. have no detectable viral load 12 weeks after the beginning of the treatment. These data will be available during the fourth quarter of 2011. The study will also measure the patients' Sustained Virologic Response (SVR), i.e. the treatment's long term effects on the viral load, up to 24 weeks after the end of the treatment, as well as TG4040's ability to elicit an immune response. An additional expected outcome of the study is to identify molecular biomarkers related to TG4040 efficacy in combination with the standard of care. Final data are expected in the fourth quarter of 2012.
"We look forward to obtaining the first results of the study in order to begin preparing the next steps of the development of this promising product candidate for the treatment of patients suffering from chronic hepatitis C, a disease with a growing incidence and which is becoming a public health concern even in the most economically developed countries." stated Philippe Archinard, Chairman and CEO of Transgene.
About TG4040
Transgene's TG4040 vaccine candidate is a recombinant vector based on the MVA virus carrying and expressing three of the major non-structural proteins (NS3, NS4 and NS5B) of the hepatitis C virus ("HCV"). The MVA vector is a highly attenuated strain of vaccinia virus, which has been tested extensively in humans as a vaccine against smallpox and is known to strongly stimulate innate and adaptive immune responses to antigens.
About TG4040 clinical development program
Phase I clinical results in 39 treatment naïve genotype 1 HCV patients showed that the product is safe and well tolerated at all dose levels tested. Immunological analyses on 15 treatment naive patients were encouraging and supported the expected mechanism of action of TG4040 which aims at inducing an effective HCV-specific T cell based immune response, able to control viral replication.
About chronic hepatitis C
Hepatitis C currently represents a major public health concern. The population chronically infected with HCV in the world is estimated at 170 to 200 million and hepatitis-C-related deaths at approximately 470,000 annually. Peak of prevalence of HCV-related diseases is expected to occur in 2025-2030 in developed countries.
HCV infection leads to liver diseases such as fibrosis, cirrhosis and liver carcinoma, which are the prime indications for liver transplants. The current standard of care for patients infected with the HCV genotype 1 (a combination of Pegylated Interferon a and Ribavirin) is lengthy, often poorly tolerated and effective in only approximately 50% of patients completing therapy. In addition, a substantial number of patients never receive therapy. Therefore, there is a strong medical need for new alternative approaches, including combination therapies.
About Transgene
Transgene is a France-based biopharmaceutical company focused on the development of therapeutic vaccines and immunotherapeutic products in oncology and infectious diseases. The Company has four compounds in Phase II clinical trials: TG4010, JX594/TG6006, TG4001/RG3484 and TG4040 and one compound in Phase I clinical trial: TG4023. Transgene has entered into strategic collaborative agreements for the development of two of its immunotherapy products:
An option agreement with Novartis for an exclusive license to develop TG4010 for the treatment of various cancers, including non small cell lung cancer (NSCLC)
An in-licensing agreement with US-based Jennerex Biotherapeutics, Inc., to develop and market JX594 (JX594/TG6006), an oncolytic product. Transgene has bio-manufacturing capacities for viral-based vectors. Additional information about Transgene can be found at http://www.transgene.fr/.
Disclaimer:
This press release contains forward-looking statements referring to the clinical testing and development of Transgene's product candidates. Clinical testing and successful product development depend on a variety of factors, including the timing and success of future patient enrolment and the risk of unanticipated adverse patient reactions. Results from future studies with more data may show less favorable outcomes than prior studies, and there is no certainty that product candidates will ever demonstrate adequate therapeutic efficacy or achieve regulatory approval or commercial use. For further information on the risks and uncertainties involved in the testing and development of Transgene's product candidates, see Trangene's Document de Référence on file with the French Autorité des marchés financiers on its website at http://www.amf-france.org/ and Transgene's website at http://www.transgene.fr/.
Société anonyme au capital de 72.470.137 € - R.C. Strasbourg B 317 540 581
Boulevard Gonthier d'Andernach - Parc d'Innovation - CS80166 - 67405 ILLKIRCH GRAFFENSTADEN CEDEX (France)
Tél : + 33 (0)3 88 27 91 00 - Fax : + 33 (0)3 88 27 91 11
Contacts:
Transgene
Philippe Archinard, CEO
Phone: +33 (0)3 88 27 91 22
or
Stéphane Boissel, Executive Vice President&CFO
Phone: +33 (0)3 88 27 91 02
or
Elisabetta Castelli, Director IR
Phone: +33 (0)1 44 08 55 05
or
MC Services
Raimund Gabriel
Phone: +49 89 210 228 30
or
Shaun Brown
Phone: +44 207 148 5998
Source
Transgene S.A. (Paris:TNG)(Euronext Paris: FR0005175080) announces that, with 154 patients randomized and treated, the enrolment of patients in the phase II HCVac trial is now complete. This study explores the combination of TG4040 (MVA-HCV) with standard of care (Pegylated-Interferon a2a and Ribavarin) in treatment naive patients with chronic genotype 1 hepatitis C.
The patients were recruited in five countries in Europe, in the United States and in Israel, and were randomized in the three arms of the study (one control arm without TG4040 and two experimental arms). HCVac investigates the efficacy and safety of two different schedules of administration of TG4040 administered in subcutaneous injections at the dose of 107 pfu in combination with the standard of care.
HCVac will measure the proportion of patients who achieve complete Early Virologic Response (cEVR), i.e. have no detectable viral load 12 weeks after the beginning of the treatment. These data will be available during the fourth quarter of 2011. The study will also measure the patients' Sustained Virologic Response (SVR), i.e. the treatment's long term effects on the viral load, up to 24 weeks after the end of the treatment, as well as TG4040's ability to elicit an immune response. An additional expected outcome of the study is to identify molecular biomarkers related to TG4040 efficacy in combination with the standard of care. Final data are expected in the fourth quarter of 2012.
"We look forward to obtaining the first results of the study in order to begin preparing the next steps of the development of this promising product candidate for the treatment of patients suffering from chronic hepatitis C, a disease with a growing incidence and which is becoming a public health concern even in the most economically developed countries." stated Philippe Archinard, Chairman and CEO of Transgene.
About TG4040
Transgene's TG4040 vaccine candidate is a recombinant vector based on the MVA virus carrying and expressing three of the major non-structural proteins (NS3, NS4 and NS5B) of the hepatitis C virus ("HCV"). The MVA vector is a highly attenuated strain of vaccinia virus, which has been tested extensively in humans as a vaccine against smallpox and is known to strongly stimulate innate and adaptive immune responses to antigens.
About TG4040 clinical development program
Phase I clinical results in 39 treatment naïve genotype 1 HCV patients showed that the product is safe and well tolerated at all dose levels tested. Immunological analyses on 15 treatment naive patients were encouraging and supported the expected mechanism of action of TG4040 which aims at inducing an effective HCV-specific T cell based immune response, able to control viral replication.
About chronic hepatitis C
Hepatitis C currently represents a major public health concern. The population chronically infected with HCV in the world is estimated at 170 to 200 million and hepatitis-C-related deaths at approximately 470,000 annually. Peak of prevalence of HCV-related diseases is expected to occur in 2025-2030 in developed countries.
HCV infection leads to liver diseases such as fibrosis, cirrhosis and liver carcinoma, which are the prime indications for liver transplants. The current standard of care for patients infected with the HCV genotype 1 (a combination of Pegylated Interferon a and Ribavirin) is lengthy, often poorly tolerated and effective in only approximately 50% of patients completing therapy. In addition, a substantial number of patients never receive therapy. Therefore, there is a strong medical need for new alternative approaches, including combination therapies.
About Transgene
Transgene is a France-based biopharmaceutical company focused on the development of therapeutic vaccines and immunotherapeutic products in oncology and infectious diseases. The Company has four compounds in Phase II clinical trials: TG4010, JX594/TG6006, TG4001/RG3484 and TG4040 and one compound in Phase I clinical trial: TG4023. Transgene has entered into strategic collaborative agreements for the development of two of its immunotherapy products:
An option agreement with Novartis for an exclusive license to develop TG4010 for the treatment of various cancers, including non small cell lung cancer (NSCLC)
An in-licensing agreement with US-based Jennerex Biotherapeutics, Inc., to develop and market JX594 (JX594/TG6006), an oncolytic product. Transgene has bio-manufacturing capacities for viral-based vectors. Additional information about Transgene can be found at http://www.transgene.fr/.
Disclaimer:
This press release contains forward-looking statements referring to the clinical testing and development of Transgene's product candidates. Clinical testing and successful product development depend on a variety of factors, including the timing and success of future patient enrolment and the risk of unanticipated adverse patient reactions. Results from future studies with more data may show less favorable outcomes than prior studies, and there is no certainty that product candidates will ever demonstrate adequate therapeutic efficacy or achieve regulatory approval or commercial use. For further information on the risks and uncertainties involved in the testing and development of Transgene's product candidates, see Trangene's Document de Référence on file with the French Autorité des marchés financiers on its website at http://www.amf-france.org/ and Transgene's website at http://www.transgene.fr/.
Société anonyme au capital de 72.470.137 € - R.C. Strasbourg B 317 540 581
Boulevard Gonthier d'Andernach - Parc d'Innovation - CS80166 - 67405 ILLKIRCH GRAFFENSTADEN CEDEX (France)
Tél : + 33 (0)3 88 27 91 00 - Fax : + 33 (0)3 88 27 91 11
Contacts:
Transgene
Philippe Archinard, CEO
Phone: +33 (0)3 88 27 91 22
or
Stéphane Boissel, Executive Vice President&CFO
Phone: +33 (0)3 88 27 91 02
or
Elisabetta Castelli, Director IR
Phone: +33 (0)1 44 08 55 05
or
MC Services
Raimund Gabriel
Phone: +49 89 210 228 30
or
Shaun Brown
Phone: +44 207 148 5998
Source
Data suggest liver experts should take care when prescribing novel antiviral HCV drugs
Public release date: 2-Apr-2011
Contact: Travis Taylor
easlpressoffice@cohnwolfe.com
44-784-306-9451
European Association for the Study of the Liver
Rapid resistance to novel anti-viral therapy develops in response to direct antiviral drugs
Berlin, Germany, Saturday 02 April 2011: Data presented at the International Liver CongressTM highlight the fact that new novel antiviral compounds for the treatment of hepatitis C virus (HCV) must be prescribed and monitored by experts and specialists to ensure resistance is minimised.1,2,3,4,5,6
Several studies observed the rapid onset of HCV resistance in patients treated with NS3-protease, NS5b-polymerase and NS5a inhibitors. Although these direct anti-virals are effective in both treatment-naive HCV patients and those who've been previously unresponsive to current treatment options, the development of resistant viral variants may cause problems in the future. In fact, two studies found HCV strains resistant to novel antiviral compounds pre-existed in patients who had never previously been exposed to the new antiviral compounds. In these patients, the variants were selected out by treatment.
Professor Heiner Wedemeyer, EASL's Secretary General, said: "While the regulatory approval of these new treatments is a highly anticipated milestone in HCV therapy, these studies show that care must be taken in the prescription and use of the new compounds. What we want to avoid is a rapid spread of HCV resistance within the patient population, which could drastically lower the effectiveness of the new drugs."
The current standard of care for chronic HCV is the combination of pegylated interferon-alfa and ribavirin, but only 40-54% of patients infected with HCV genotype 1 achieve a sustained virological response (SVR).7,8 Novel antiviral therapeutics are much sought after to treat patients who don't respond to the current standard of care. As such, a large number of new drugs for HCV are at various stages of preclinical and clinical development.9
However, as each new copy of the HCV genome exhibits on average one nucleotide change per replication cycle, HCV's replication machinery allows the virus to quickly come up with mutations that render it resistant to antiviral drugs. This is a major concern for successful anti-HCV therapy.10
NS3 protease inhibitors block the function of the HCV NS3 protease, an enzyme essential for HCV's replication. NS5A replication complex inhibitors block the function of HCV nonstructural protein 5A, a multifunctional protein essential for HCV replication.10
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. McPhee F et al. Charactarizaion of virologic escape in HCV gentotype 1 null responders receiving a combination of the NS3 protease inhibitor BMS-650032 and NS5A inhibitor BMS-790052. Abstract presented at The International Liver CongressTM 2011
2. Chevaliez S et a. Molecular characterization of HCV resistance to telaprevir by means of ultra-deep pyrosequencing: pre-existing resistant variants and dynamics of resistant populations. Abstract presented at The International Liver CongressTM 2011
3. Hebner C et al. Emergence and persistence of ns5b mutations following combination treatment with tegobuvir (gs-9190) plus standard of care--long-term follow-up from the phase iib study gs-us-196-0103. Abstract presented at The International Liver CongressTM 2011
4. Zeuzem S et al. Boceprevir Resistance-Associated Variants (RAVs) are observed more frequently in HCV (gt1)-infected Patients with poor response to peginterferon alfa- 2B/ribavirin. Abstract presented at The International Liver CongressTM 2011 (1621)
5. Svarovskaia E et al. Abundant minority drug-resistant ns3 mutants detected by deep sequencing in hcv patients as early as 24 hours after initiating antiviral treatment. Abstract presented at the international liver congresstm 2011 (1773)
6. Sullivan J et al. Evolution of Treatment-Emergent Resistant Variants in Telaprevir Phase 3 Clinical Trials. (1783)
7. Fried M.W et al. "Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection." New England Journal of Medicine 347.13 (2002): 975-82
8. Hadziyannis S J et al. "Peginterferon-alpha 2a and ribavirin combination therapy in chronic hepatitis C - A randomized study of treatment duration and ribavirin dose." Annals of Internal Medicine 140.5 (2004): 346-55.
9. Shiffman M L. "Treatment of hepatits C in 2011:what can we expect?" Curr.Gastroenterol.Rep. 12 (2010): 70-75
10. Raffaele De Francesco and Giovanni Migliaccio (2005). Challenges and successes in developing new therapies for hepatitis C. Nature, 436, 953-960
Source
Contact: Travis Taylor
easlpressoffice@cohnwolfe.com
44-784-306-9451
European Association for the Study of the Liver
Rapid resistance to novel anti-viral therapy develops in response to direct antiviral drugs
Berlin, Germany, Saturday 02 April 2011: Data presented at the International Liver CongressTM highlight the fact that new novel antiviral compounds for the treatment of hepatitis C virus (HCV) must be prescribed and monitored by experts and specialists to ensure resistance is minimised.1,2,3,4,5,6
Several studies observed the rapid onset of HCV resistance in patients treated with NS3-protease, NS5b-polymerase and NS5a inhibitors. Although these direct anti-virals are effective in both treatment-naive HCV patients and those who've been previously unresponsive to current treatment options, the development of resistant viral variants may cause problems in the future. In fact, two studies found HCV strains resistant to novel antiviral compounds pre-existed in patients who had never previously been exposed to the new antiviral compounds. In these patients, the variants were selected out by treatment.
Professor Heiner Wedemeyer, EASL's Secretary General, said: "While the regulatory approval of these new treatments is a highly anticipated milestone in HCV therapy, these studies show that care must be taken in the prescription and use of the new compounds. What we want to avoid is a rapid spread of HCV resistance within the patient population, which could drastically lower the effectiveness of the new drugs."
The current standard of care for chronic HCV is the combination of pegylated interferon-alfa and ribavirin, but only 40-54% of patients infected with HCV genotype 1 achieve a sustained virological response (SVR).7,8 Novel antiviral therapeutics are much sought after to treat patients who don't respond to the current standard of care. As such, a large number of new drugs for HCV are at various stages of preclinical and clinical development.9
However, as each new copy of the HCV genome exhibits on average one nucleotide change per replication cycle, HCV's replication machinery allows the virus to quickly come up with mutations that render it resistant to antiviral drugs. This is a major concern for successful anti-HCV therapy.10
NS3 protease inhibitors block the function of the HCV NS3 protease, an enzyme essential for HCV's replication. NS5A replication complex inhibitors block the function of HCV nonstructural protein 5A, a multifunctional protein essential for HCV replication.10
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. McPhee F et al. Charactarizaion of virologic escape in HCV gentotype 1 null responders receiving a combination of the NS3 protease inhibitor BMS-650032 and NS5A inhibitor BMS-790052. Abstract presented at The International Liver CongressTM 2011
2. Chevaliez S et a. Molecular characterization of HCV resistance to telaprevir by means of ultra-deep pyrosequencing: pre-existing resistant variants and dynamics of resistant populations. Abstract presented at The International Liver CongressTM 2011
3. Hebner C et al. Emergence and persistence of ns5b mutations following combination treatment with tegobuvir (gs-9190) plus standard of care--long-term follow-up from the phase iib study gs-us-196-0103. Abstract presented at The International Liver CongressTM 2011
4. Zeuzem S et al. Boceprevir Resistance-Associated Variants (RAVs) are observed more frequently in HCV (gt1)-infected Patients with poor response to peginterferon alfa- 2B/ribavirin. Abstract presented at The International Liver CongressTM 2011 (1621)
5. Svarovskaia E et al. Abundant minority drug-resistant ns3 mutants detected by deep sequencing in hcv patients as early as 24 hours after initiating antiviral treatment. Abstract presented at the international liver congresstm 2011 (1773)
6. Sullivan J et al. Evolution of Treatment-Emergent Resistant Variants in Telaprevir Phase 3 Clinical Trials. (1783)
7. Fried M.W et al. "Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection." New England Journal of Medicine 347.13 (2002): 975-82
8. Hadziyannis S J et al. "Peginterferon-alpha 2a and ribavirin combination therapy in chronic hepatitis C - A randomized study of treatment duration and ribavirin dose." Annals of Internal Medicine 140.5 (2004): 346-55.
9. Shiffman M L. "Treatment of hepatits C in 2011:what can we expect?" Curr.Gastroenterol.Rep. 12 (2010): 70-75
10. Raffaele De Francesco and Giovanni Migliaccio (2005). Challenges and successes in developing new therapies for hepatitis C. Nature, 436, 953-960
Source
EASL: New data presented today at the International Liver CongressTM confirm the antiviral activity of fluvastatin -- commonly used as a cholesterol-lowering treatment -- in patients with chronic hepatitis C (HCV).
Published on: 2011-03-31
Patients had improved early and sustained virological response (EVR and SVR) when treated with the current standard of care – pegylated Interferon-alpha and ribavirin (PegIFN/RBV) – and fluvastatin. The results show patients receiving fluvastatin and PegIFN/RBV achieve higher rates of EVR and SVR – 75.96% and 63.46% – to those receiving placebo and PegIFN/RBV – 61.9% and 49.52% respectively.
EASL's Secretary General, Professor Heiner Wedemeyer, said: "We know that metabolic syndrome (MS), the main treatment indication for statins, is associated with severe fibrosis and lower treatment responses in chronic HCV patients. The confirmation that the combination of fluvastatin and PegIFN/RBV could provide better clinical outcomes for those patients with co-morbid chronic HCV and MS is very exciting for clinicians".
Even in patients without MS, the study shows that responses to treatment are still higher in patients treated with fluvastatin and PegIFN/RBV (EVR 85.36% versus 71.42% and SVR 74.39% vs. 58.44).
"Today, healthcare professionals have to be mindful when considering health provision and treatment costs. We cannot overlook the importance of opportunities to maximise more affordable drugs' potential to complement the current standard of care for chronic HCV management," said Professor Wedemeyer.
This new study concludes that the synergistic effects between fluvastatin and PegIFN/RBV shows lipid lowering drugs may favour HCV clearance and be useful as a chronic HCV treatment, irrespective of the presence of metabolic syndrome.
###
Travis Taylor
easlpressoffice@cohnwolfe.com
44-784-306-9451
Source
Patients had improved early and sustained virological response (EVR and SVR) when treated with the current standard of care – pegylated Interferon-alpha and ribavirin (PegIFN/RBV) – and fluvastatin. The results show patients receiving fluvastatin and PegIFN/RBV achieve higher rates of EVR and SVR – 75.96% and 63.46% – to those receiving placebo and PegIFN/RBV – 61.9% and 49.52% respectively.
EASL's Secretary General, Professor Heiner Wedemeyer, said: "We know that metabolic syndrome (MS), the main treatment indication for statins, is associated with severe fibrosis and lower treatment responses in chronic HCV patients. The confirmation that the combination of fluvastatin and PegIFN/RBV could provide better clinical outcomes for those patients with co-morbid chronic HCV and MS is very exciting for clinicians".
Even in patients without MS, the study shows that responses to treatment are still higher in patients treated with fluvastatin and PegIFN/RBV (EVR 85.36% versus 71.42% and SVR 74.39% vs. 58.44).
"Today, healthcare professionals have to be mindful when considering health provision and treatment costs. We cannot overlook the importance of opportunities to maximise more affordable drugs' potential to complement the current standard of care for chronic HCV management," said Professor Wedemeyer.
This new study concludes that the synergistic effects between fluvastatin and PegIFN/RBV shows lipid lowering drugs may favour HCV clearance and be useful as a chronic HCV treatment, irrespective of the presence of metabolic syndrome.
###
Travis Taylor
easlpressoffice@cohnwolfe.com
44-784-306-9451
Source
EASL: REG-Novartis first-in-class antiviral DEB025 achieved sustained viral response in 76% of patients with chronic hepatitis C, new phase II study shows
Thu Mar 31, 2011 17:30 CET
◦ DEB025 plus standard of care (pegylated-interferon alfa 2a/ribavirin) showed superior viral cure vs standard of care alone (p=0.008)[1]
◦ A cyclophilin inhibitor, DEB025 belongs to a new class of medicines that limit hepatitis C virus replication and have the potential to reshape hepatitis C therapy
◦ Phase III study with DEB025 commenced recently with previously untreated patients infected by the most common form of hepatitis C virus
Basel, March 31, 2011 - Novartis announced today that a Phase II study with the first-in-class antiviral DEB025 (alisporivir) met its primary endpoint for achieving viral cure (24 weeks after stopping treatment) in 76% of patients with chronic hepatitis C[1]. The study involved nearly 300 previously untreated patients infected with the most common form of hepatitis C virus (HCV), the genotype 1 (G1)[1].
The data were presented today at the European Association for the Study of the Liver (EASL) congress in Berlin, Germany. The findings show that 76% of G1 chronic hepatitis C patients treated with DEB025 plus standard of care (pegylated-interferon alfa 2a/ribavirin) achieved superior viral cure (known as sustained viral response, or SVR) compared to 55% of patients on standard of care alone (p=0.008)[1]. Treatment with DEB025 demonstrated a low incidence of adverse events, with discontinuation rates comparable between treatment groups[1].
"Hepatitis C is difficult to treat and current therapies are only effective in about half of patients infected with the most prevalent genotype of HCV[2]," said Stefan Zeuzem, Professor of Medicine at the Goethe University Hospital in Frankfurt, Germany, and the study's principal investigator. "These results are exciting because a large majority of patients achieved sustained viral response with DEB025, with some who also benefited from a shorter duration of treatment compared to standard therapy[1]."
DEB025 is the first in a new class of drugs called cyclophilin inhibitors. Unlike other compounds in development that target the virus directly, DEB025 is a host targeting antiviral (HTA) that targets so-called host proteins which are essential for the replication of HCV. As these proteins play a key role in the replication of all types of HCV, DEB025 may offer an effective treatment option for a broad range of HCV forms. In other clinical trials, DEB025 has also shown effective antiviral activity against other common HCV genotypes (G2, G3 and G4)[3].
"There is a critical need for more effective drugs to treat chronic hepatitis C, and Novartis is dedicated to developing medicines that will reduce the burden of this disease for patients and physicians," said Trevor Mundel, MD, Global Head of Development at Novartis Pharma AG. "DEB025 has a new mode of action that may stop the virus from replicating and could reshape the future approach to treatment of hepatitis C."
More than 170 million people worldwide are infected with HCV, which can cause serious liver disease leading to cirrhosis, liver cancer, and in some cases death. HCV is a blood borne virus that predominantly affects the liver[4],[5]. As an RNA (ribonucleic acid) virus, it mutates much more than DNA (deoxyribonucleic acid) viruses. This ability to change makes it harder for the immune system to clear (or eliminate) the virus. There are six major variations of HCV, known as genotypes and labelled from G1 to G6[5].
The study presented at EASL was a 48-week, global, double-blind, randomized, placebo-controlled trial in G1 treatment-naïve chronic hepatitis C patients. It evaluated the efficacy and safety of DEB025 combined with pegylated-interferon alfa 2a/ribavirin (PegIFN/RBV) vs. PegIFN/RBV alone. The primary endpoint was sustained viral response after 24 weeks (SVR24)[1].
Transient and reversible increase in bilirubin was observed in association with the initial DEB025 loading dose[1]. A small proportion of patients (4.2%) had a transient increase in bilirubin more than five times the upper limit of normal (ULN), but this was not associated with liver damage[1].
A pivotal Phase III study with DEB025 commenced recently to evaluate the efficacy and safety of DEB025 combined with standard of care and enrolling previously untreated HCV G1 patients. Other Phase II studies are ongoing in other patient populations i.e., G1 treatment-experienced patients and G2 and G3 treatment-naive patients.
Novartis in-licensed DEB025 from Debiopharm Group(TM), an independent biopharmaceuticals company based in Switzerland, under an agreement which gives Novartis exclusive worldwide development, manufacturing and marketing rights (excluding Japan).
Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "potential," "exciting," "may," "dedicated," "will," "could," "launched," or similar expressions, or by express or implied discussions regarding potential marketing submissions or approvals for DEB025, or the potential timing of any such submissions or approvals, or regarding potential future revenues from DEB025. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with DEB025 to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that DEB025 will be submitted or approved for sale in any market. Nor can there be any guarantee that DEB025 will achieve any particular levels of revenue in the future. In particular, management's expectations regarding DEB025 could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise
About Novartis
Novartis provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2010, the Group's continuing operations achieved net sales of USD 50.6 billion, while approximately USD 9.1 billion (USD 8.1 billion excluding impairment and amortization charges) was invested in R&D throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 119,000 full-time-equivalent associates (including 16,700 Alcon associates) and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com/.
References
[1] Flisiak R, Pawlotsky JM, Crabbe R, Kryczka W, Haüssinger D, Mazella G, Romero-Gomez M, Purcea D, Vuagniaux G, Bao W, Zeuzem S. Once-daily alisporivir (DEB025) plus pegifnalfa2a/ribavirin results in superior sustained virologic response (SVR24) in chronic hepatitis C genotype 1 treatment naïve patients. Presented at European Association for Study of the Liver Congress, Berlin, March 2011.
[2] Hoofnagle JH. A step forward in therapy for hepatitis C. N Engl J Med. 2009; 360 (18):1899-901.
[3] Flisiak R, et al. The cyclophilin inhibitor Debio 025 combined with peg IFNa2a significantly reduces viral load in treatment-naïve hepatitis C patients. Hepatology. 2009; 49:1460-68.
[4] Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001; 345 (1):41-52.
[5] World Hepatitis Alliance, http://www.worldhepatitisalliance.org/, Last accessed March 2011
Novartis Media Relations
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Source
◦ DEB025 plus standard of care (pegylated-interferon alfa 2a/ribavirin) showed superior viral cure vs standard of care alone (p=0.008)[1]
◦ A cyclophilin inhibitor, DEB025 belongs to a new class of medicines that limit hepatitis C virus replication and have the potential to reshape hepatitis C therapy
◦ Phase III study with DEB025 commenced recently with previously untreated patients infected by the most common form of hepatitis C virus
Basel, March 31, 2011 - Novartis announced today that a Phase II study with the first-in-class antiviral DEB025 (alisporivir) met its primary endpoint for achieving viral cure (24 weeks after stopping treatment) in 76% of patients with chronic hepatitis C[1]. The study involved nearly 300 previously untreated patients infected with the most common form of hepatitis C virus (HCV), the genotype 1 (G1)[1].
The data were presented today at the European Association for the Study of the Liver (EASL) congress in Berlin, Germany. The findings show that 76% of G1 chronic hepatitis C patients treated with DEB025 plus standard of care (pegylated-interferon alfa 2a/ribavirin) achieved superior viral cure (known as sustained viral response, or SVR) compared to 55% of patients on standard of care alone (p=0.008)[1]. Treatment with DEB025 demonstrated a low incidence of adverse events, with discontinuation rates comparable between treatment groups[1].
"Hepatitis C is difficult to treat and current therapies are only effective in about half of patients infected with the most prevalent genotype of HCV[2]," said Stefan Zeuzem, Professor of Medicine at the Goethe University Hospital in Frankfurt, Germany, and the study's principal investigator. "These results are exciting because a large majority of patients achieved sustained viral response with DEB025, with some who also benefited from a shorter duration of treatment compared to standard therapy[1]."
DEB025 is the first in a new class of drugs called cyclophilin inhibitors. Unlike other compounds in development that target the virus directly, DEB025 is a host targeting antiviral (HTA) that targets so-called host proteins which are essential for the replication of HCV. As these proteins play a key role in the replication of all types of HCV, DEB025 may offer an effective treatment option for a broad range of HCV forms. In other clinical trials, DEB025 has also shown effective antiviral activity against other common HCV genotypes (G2, G3 and G4)[3].
"There is a critical need for more effective drugs to treat chronic hepatitis C, and Novartis is dedicated to developing medicines that will reduce the burden of this disease for patients and physicians," said Trevor Mundel, MD, Global Head of Development at Novartis Pharma AG. "DEB025 has a new mode of action that may stop the virus from replicating and could reshape the future approach to treatment of hepatitis C."
More than 170 million people worldwide are infected with HCV, which can cause serious liver disease leading to cirrhosis, liver cancer, and in some cases death. HCV is a blood borne virus that predominantly affects the liver[4],[5]. As an RNA (ribonucleic acid) virus, it mutates much more than DNA (deoxyribonucleic acid) viruses. This ability to change makes it harder for the immune system to clear (or eliminate) the virus. There are six major variations of HCV, known as genotypes and labelled from G1 to G6[5].
The study presented at EASL was a 48-week, global, double-blind, randomized, placebo-controlled trial in G1 treatment-naïve chronic hepatitis C patients. It evaluated the efficacy and safety of DEB025 combined with pegylated-interferon alfa 2a/ribavirin (PegIFN/RBV) vs. PegIFN/RBV alone. The primary endpoint was sustained viral response after 24 weeks (SVR24)[1].
Transient and reversible increase in bilirubin was observed in association with the initial DEB025 loading dose[1]. A small proportion of patients (4.2%) had a transient increase in bilirubin more than five times the upper limit of normal (ULN), but this was not associated with liver damage[1].
A pivotal Phase III study with DEB025 commenced recently to evaluate the efficacy and safety of DEB025 combined with standard of care and enrolling previously untreated HCV G1 patients. Other Phase II studies are ongoing in other patient populations i.e., G1 treatment-experienced patients and G2 and G3 treatment-naive patients.
Novartis in-licensed DEB025 from Debiopharm Group(TM), an independent biopharmaceuticals company based in Switzerland, under an agreement which gives Novartis exclusive worldwide development, manufacturing and marketing rights (excluding Japan).
Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "potential," "exciting," "may," "dedicated," "will," "could," "launched," or similar expressions, or by express or implied discussions regarding potential marketing submissions or approvals for DEB025, or the potential timing of any such submissions or approvals, or regarding potential future revenues from DEB025. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with DEB025 to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that DEB025 will be submitted or approved for sale in any market. Nor can there be any guarantee that DEB025 will achieve any particular levels of revenue in the future. In particular, management's expectations regarding DEB025 could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise
About Novartis
Novartis provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2010, the Group's continuing operations achieved net sales of USD 50.6 billion, while approximately USD 9.1 billion (USD 8.1 billion excluding impairment and amortization charges) was invested in R&D throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 119,000 full-time-equivalent associates (including 16,700 Alcon associates) and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com/.
References
[1] Flisiak R, Pawlotsky JM, Crabbe R, Kryczka W, Haüssinger D, Mazella G, Romero-Gomez M, Purcea D, Vuagniaux G, Bao W, Zeuzem S. Once-daily alisporivir (DEB025) plus pegifnalfa2a/ribavirin results in superior sustained virologic response (SVR24) in chronic hepatitis C genotype 1 treatment naïve patients. Presented at European Association for Study of the Liver Congress, Berlin, March 2011.
[2] Hoofnagle JH. A step forward in therapy for hepatitis C. N Engl J Med. 2009; 360 (18):1899-901.
[3] Flisiak R, et al. The cyclophilin inhibitor Debio 025 combined with peg IFNa2a significantly reduces viral load in treatment-naïve hepatitis C patients. Hepatology. 2009; 49:1460-68.
[4] Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001; 345 (1):41-52.
[5] World Hepatitis Alliance, http://www.worldhepatitisalliance.org/, Last accessed March 2011
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Source
EASL: Results show benefits in using acute kidney injury criteria in the diagnosis of cirrhosis
Public release date: 31-Mar-2011
Contact: Dimple Natali
easlpressoffice@cohnwolfe.com
44-797-160-8315
European Association for the Study of the Liver
Recent study may change future approach to diagnosis
The first clinical study investigating the use of the AKIN criteria (Acute Kidney Injury Network) in cirrhosis has shown significant benefits that have the potential to change future diagnosis, according to results from a Spanish study presented today at the International Liver Congress.
As screening and differential diagnosis is becoming increasingly important in relation to managing health service provision, if these results are confirmed in larger studies, the AKIN criteria has the potential to replace current screening and diagnosis criteria in hospitalised cirrhotic patients.
This prospective study aimed to assess the value of the AKIN criteria in predicting outcomes in hospitalised cirrhotic patients. Out of 300 patients admitted to hospital for complications of cirrhosis 88 (29%) developed renal failure according to the AKIN criteria. Three-month survival of these patients was 38%, compared with 87% of patients who did not develop renal failure (p< 0.01).
Renal failure in cirrhosis is currently defined as serum creatinine greater than 1.5 mg/dL. According to the study investigators this definition has two shortcomings: firstly it represents a very low glomerular filtration rate (GFR), and secondly it may not detect significant changes in GFR because it does not take into account variations in creatinine values. In contrast, the AKIN criteria is much more sensitive and considers renal failure as an increase in serum creatinine greater than or equal to a 0.3ml/dL (≥50% increase) compared to baseline within 48 hours.
Mark Thursz, EASL's Vice-Secretary commented: "Liver disease is associated with a high mortality due to renal failure, especially in end stage cirrhosis. As experts and clinicians in the field of hepatology, defining more sensitive tests that help to identify patients at risk of renal failure or death earlier is critical to enable us to intervene and ensure the patient has the best possible outcome".
Furthermore, when the AKIN criteria were combined with the current definition of renal failure, patients meeting the AKIN criteria in whom serum creatinine reached a peak value of >1.5 mg/dL (n=60) had a significantly lower survival compared to patients with a peak value ≤ 1.5 mg/dL (n=28) (29% vs 58%, respectively; p=0.026). Out of the 300 patients, 30 patients had serum creatinine >1.5 mg/dL but did not meet the AKIN criteria. However, three-month survival of these patients was 80%.
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. Fagundes C et al. Acute Kidney Injury Network (AKIN) Criteria for Acute Renal Failure Predicts Outcome in Hospitalized Cirrhotic Patients. A Prospective Study. Presented at The International Liver CongressTM 2011
Source
Contact: Dimple Natali
easlpressoffice@cohnwolfe.com
44-797-160-8315
European Association for the Study of the Liver
Recent study may change future approach to diagnosis
The first clinical study investigating the use of the AKIN criteria (Acute Kidney Injury Network) in cirrhosis has shown significant benefits that have the potential to change future diagnosis, according to results from a Spanish study presented today at the International Liver Congress.
As screening and differential diagnosis is becoming increasingly important in relation to managing health service provision, if these results are confirmed in larger studies, the AKIN criteria has the potential to replace current screening and diagnosis criteria in hospitalised cirrhotic patients.
This prospective study aimed to assess the value of the AKIN criteria in predicting outcomes in hospitalised cirrhotic patients. Out of 300 patients admitted to hospital for complications of cirrhosis 88 (29%) developed renal failure according to the AKIN criteria. Three-month survival of these patients was 38%, compared with 87% of patients who did not develop renal failure (p< 0.01).
Renal failure in cirrhosis is currently defined as serum creatinine greater than 1.5 mg/dL. According to the study investigators this definition has two shortcomings: firstly it represents a very low glomerular filtration rate (GFR), and secondly it may not detect significant changes in GFR because it does not take into account variations in creatinine values. In contrast, the AKIN criteria is much more sensitive and considers renal failure as an increase in serum creatinine greater than or equal to a 0.3ml/dL (≥50% increase) compared to baseline within 48 hours.
Mark Thursz, EASL's Vice-Secretary commented: "Liver disease is associated with a high mortality due to renal failure, especially in end stage cirrhosis. As experts and clinicians in the field of hepatology, defining more sensitive tests that help to identify patients at risk of renal failure or death earlier is critical to enable us to intervene and ensure the patient has the best possible outcome".
Furthermore, when the AKIN criteria were combined with the current definition of renal failure, patients meeting the AKIN criteria in whom serum creatinine reached a peak value of >1.5 mg/dL (n=60) had a significantly lower survival compared to patients with a peak value ≤ 1.5 mg/dL (n=28) (29% vs 58%, respectively; p=0.026). Out of the 300 patients, 30 patients had serum creatinine >1.5 mg/dL but did not meet the AKIN criteria. However, three-month survival of these patients was 80%.
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. Fagundes C et al. Acute Kidney Injury Network (AKIN) Criteria for Acute Renal Failure Predicts Outcome in Hospitalized Cirrhotic Patients. A Prospective Study. Presented at The International Liver CongressTM 2011
Source
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