Bristol-Myers Squibb Company (NYSE: BMY) today announced the submission of a New Drug Application (NDA) to Japan’s Pharmaceutical and Medical Devices Agency seeking the world’s first interferon-free and ribavirin-free treatment regimen for patients with chronic hepatitis C. The submission is based on results from a Phase III study demonstrating that the 24-week, all-oral, interferon-free and ribavirin-free regimen of daclatasvir (DCV) and asunaprevir (ASV) achieved an overall sustained virologic response 24 weeks after the end of treatment (SVR 24) of 84.7% in Japanese patients with chronic hepatitis C (HCV) genotype 1b who were either interferon-ineligible/intolerant (87.4% SVR 24) or non-responders (null and partial) to interferon-based therapies (80.5% SVR 24). These Phase III data will lead the Presidential Plenary at the Viral Hepatitis Session on November 5 during the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington D.C. Globally, there are 170 million people who are infected with HCV. Of the 1.2 million people living with HCV in Japan, approximately 70 percent of these patients have genotype 1b, which has one of the lowest response rates to current treatments. Further, a significant number of patients with HCV in Japan are over the age of 65, leading to more disease-related complications and a decreased likelihood of tolerating interferon-based therapies, the standard for treating HCV. “With our submission in Japan, we are pleased to be one step closer to bringing a potential new treatment option to the many people living with HCV in that country,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “The all-oral regimen of DCV plus ASV in this study represents the potential for a significant advance in the treatment of HCV infection in Japan, particularly when considering that Japanese patients chronically infected with HCV are often older than in other countries and predominantly infected with genotype 1b, both factors which impact response to therapy.” The regimen used in the Phase III study resulted in low rates of discontinuation (5%) due to adverse events (AEs). In addition, the rate of serious adverse events (SAEs) was low (5.9%) and varied among patients. Nasopharyngitis was the most common adverse event in the study (30.2%, 67/222).
Study Design and ResultsIn this open-label, parallel group, Phase III study, interferon- ineligible/intolerant (IN/I) patients (n=135) and interferon/ribavirin non-responder (NR) patients (n=87) received DCV 60 mg once daily plus ASV 100 mg twice daily for 24 weeks. The primary endpoint was the percentage of patients with a sustained virologic response at 24 weeks after the end of treatment (SVR 24). Virologic Response
- High rates of SVR24 were achieved in the two studied patient populations – those IN/I patients with limited therapeutic options (87.4%, 118/135) and those NR patients typically associated with low responses to interferon-based therapies (80.5%, 70/87).
- Patients ≥ 65 years of age had SVR24 rates similar to those in patients < 65 years and age did not appear to impact response rates. SVR24 rates for those ≥ 65 years of age were 91.9% (57/62) in the IN/I elderly patient population and 85.2% (23/27) in the NR elderly population.
- There was no clinically significant difference in SVR24 by traditionally important baseline factors including gender, age, baseline HCV RNA, cirrhosis, and IL28B genotype.
- There were low rates of virologic breakthrough and EOT (end of treatment) detectable HCV RNA (17/222 patients (7.7%)), and low rates of relapse (17/205 patients (8.3%)).
The most common adverse event leading to discontinuation was ALT/AST elevation, a measure of liver inflammation. Of the 11 patients who discontinued due to an adverse event, 10 discontinued due to ALT/AST elevation. Despite early discontinuation, 80% of these patients achieved SVR 24 and all ALT/AST values returned to normal.About Bristol-Myers Squibb’s HCV Portfolio Bristol-Myers Squibb’s hepatitis C pipeline includes compounds with different mechanisms of action, pursuing both biologics as well as small molecule direct-acting antivirals. These compounds are being studied as part of multiple treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies.
- Our investigational NS5A replication complex inhibitor daclatasvir (DCV) has been extensively studied in thousands of patients to date as a foundational agent for multiple direct-acting antiviral-based (DAA) combination therapies. DCV has shown antiviral potency and pan-genotypic activity across HCV genotypes in vitro. DCV has a drug-drug interaction profile that supports its continued study in a variety of HCV combination regimens
- Asunaprevir (ASV) is an investigational NS3 protease inhibitor for hepatitis C which has been studied as a component of DCV-based treatment regimens
- BMS-791325 is a non-nucleoside inhibitor of the NS5B polymerase, currently in Phase II development for hepatitis C as a component of DCV-based treatment regimens
- Lambda is an investigational type III interferon that has the potential to offer an alternative to alfa-interferon in patients for whom an interferon-based regimen is required or preferred
About Bristol-Myers SquibbBristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews. Bristol-Myers Squibb Forward Looking Statement This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the clinical trials of these compounds will support regulatory filings, or that the compounds described in this release will receive regulatory approvals or, if approved, that they will become commercially successful products. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2012, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.