Roche Stands By Their HCV Drugs Citing "IDEAL" Study Design IssuesJanuary 28, 2008
Roche responds to announcement of “IDEAL” hepatitis C study
Brad Jenkins, Roche
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BASEL – January 14, 2008 – Following an announcement from Schering-Plough, Roche today affirmed the value of PEGASYS® (peginterferon alfa-2a) in combination with COPEGUS® (Roche’s brand of ribavirin) as the market-leading treatment for patients with hepatitis C. Despite clear biases in the design of the “IDEAL” study that potentially favoured patients taking PegIntron™ (peginterferon alfa-2b) regimens – particularly the ribavirin dose reduction protocol – the study results have shown that patients treated with a PEGASYS regimen had a similar chance of being successfully treated for hepatitis C.
“I do not expect that the results of the IDEAL study will meaningfully impact clinical practice, except to inform physicians on the appropriate dosing of PegIntron and to reinforce the already widely-accepted view that optimising ribavirin dosing throughout treatment is critical to achieving success and preventing treatment relapse in hepatitis C,” said Douglas Dieterich, M.D., Professor of Medicine in the Division of Hepatology at Mt. Sinai School of Medicine in New York, New York.
In 2001, the U.S. Food and Drug Administration (FDA) required Schering-Plough to conduct a post-approval commitment trial to determine if a lower dose of PegIntron (1.0 mcg/kg) was as effective as the approved dose of 1.5 mcg/kg, both in combination with identical ribavirin regimens.1 A third arm was added to the study in which patients received PEGASYS 180 mcg with a different ribavirin dosing schedule. This mismatch of ribavirin dosing introduces several potential biases into the study because experts agree that an optimised dose of ribavirin, with either pegylated interferon, is critical to achieving success in hepatitis C treatment. In particular, maintaining a full dose of ribavirin has shown an important ability to reduce relapse following the end of treatment.
“PEGASYS quickly became the market leader after its launch, based on robust clinical data and patient and physician preference. We are convinced that physicians and patients will continue to choose the PEGASYS plus COPEGUS combination therapy based on positive experience and sound clinical evidence,” said Rob Mitchell, Head of Viral Diseases Strategic Marketing at Roche. “Our current focus at Roche is on advancing the treatment of hepatitis C by optimising doses and duration of PEGASYS and ribavirin in patients with unmet medical need, while developing new compounds that have the potential to offer a successful outcome to even more patients.”
Roche believes that it is critical for patients and physicians to receive complete information to fully understand the results of “IDEAL” so that treatment decisions can be based on scientific data.
Please see below for additional information about the “IDEAL” trial, Roche and PEGASYS including important safety information.
“IDEAL” Trial Design Issues
- Starting doses of ribavirin were different in the PegIntron and PEGASYS arms of the study
- The design calls for a more drastic ribavirin dose reduction for side effect management in most patients in the PEGASYS arm compared to patients in the PegIntron arms; in some cases, ribavirin dose reductions for patients in the PEGASYS arm were three times greater than for patients in the PegIntron arms. This is important because a substantial number of patients being treated for hepatitis C require their ribavirin dose to be reduced to manage side effects, and this could have an impact on the efficacy of the regimen
- The PEGASYS arm was not blinded, meaning that patients and physicians knew which treatment was being administered. Many comparative studies are blinded to ensure that bias does not compromise the results
- Erythropoetin (EPO) is a medication that is often given to treat ribavirin-related anemia and help patients maintain a higher ribavirin dose. However, physicians could only prescribe EPO after the first dose ribavirin reduction in the “IDEAL” trial. Since patients in the PegIntron arms generally had smaller ribavirin dose reductions, this introduces another potential bias and means those PegIntron patients were potentially able to maintain a higher dose of ribavirin compared to PEGASYS patients
Efficacy of PEGASYS plus COPEGUS Combination Therapy
PEGASYS was launched by Roche in 2002 and quickly became the leading treatment for patients with hepatitis C. PEGASYS plus COPEGUS is the only pegylated interferon combination regimen to have demonstrated significantly superior benefits over conventional interferon combination therapy across all HCV genotypes, irrespective of viral load.2-4 The combination of PEGASYS and COPEGUS consistently shows high cure rates – up to 66% overall sustained virological response – across a number of large, randomised clinical studies including in patients with difficult-to-cure disease such as genotype 1 HCV, cirrhosis, and HIV-HCV co-infection.2-7
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolism and central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs roughly 75,000 worldwide and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai.
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- FDA letter to Schering-Plough, August 7, 2001. Accessed Nov. 26, 2007 at: http://www.fda.gov/cder/foi/appletter/2001/pegsche080701L.htm
- Swan, T. Expediency, Cost-Cutting, Expediency Trump Science in Clinical Development Plan for Peg-Intron: The head-to-head that wasn’t. TAGLine 2003: 10(10)1-4. Also available at: http://www.aidsinfonyc.org/tag/taglines/0312.pdf
- Raymond, D. The Real IDEAL: Peg-Intron vs. Pegasys. Hepatitis C Harm Reduction Project Web site. Accessed Dec. 17, 2007 at: http://hepcproject.typepad.com/hep_c_project/2004/05/the_real_ideal_.html
- Hadziyannis SJ, Sette H, Jr., Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004;140(5):346-55.
- Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004;351(5):438-50.
- Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347(13):975-82.
- Marcellin P, Brillanti S, Cheinquer H. Peginterferon alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS) is an efficacious and safe treatment for chronic hepatitis C (CHC) in patients with compensated cirrhosis. . In: 38th Annual Meeting of the European Association for the Study of the Liver (EASL) July 3-6; 2003; Geneva, Switzerland; 2003.