All-Oral Treatment Regimen of Bristol-Myers Squibb’s Investigational NS5A and NS3 Inhibitors Achieved 90% Sustained Virologic Response (SVR12) in Phase II Study Sentinel Cohort of Genotype 1b Null Responders

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) today announced results from a ten patient sentinel cohort of an ongoing Phase II study in which treatment with a dual, all-oral direct-acting antiviral (DAA) regimen of the investigational NS5A replication complex inhibitor daclatasvir (BMS-790052) and the investigational NS3 protease inhibitor asunaprevir (BMS-650032) achieved undetectable viral load at 12 weeks post-treatment (SVR12) in 90% (n=9/10) of genotype 1b hepatitis C (HCV) patients who had previously not responded to peginterferon alfa and ribavirin (alfa/RBV). Serious adverse events occurred in two patients in this study, of which one led to treatment discontinuation. The findings were presented at the 62^nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco.

“The results of this Phase II study of Bristol-Myers Squibb’s investigational, oral direct-acting antivirals are encouraging as we study potential hepatitis C therapies for this difficult-to-treat patient population.”

“Genotype 1 patients have a cure rate of about 45% when treated with interferon alfa and ribavirin. For the 55% of patients who do not achieve viral cure, further treatment has limited success, even with the addition of a protease inhibitor. There is a real unmet medical need for new treatment options that have the potential to increase response rates in null responders,” said Kazuaki Chayama, MD, PhD, Professor, Department of Medicine and Molecular Science, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. “The results of this Phase II study of Bristol-Myers Squibb’s investigational, oral direct-acting antivirals are encouraging as we study potential hepatitis C therapies for this difficult-to-treat patient population.”

Based on the sentinel cohort results, the study has been expanded to include both genotype 1b patients who are null responders (n~20) and patients ineligible for alfa/RBV for medical reasons or who discontinued alfa/RBV after less than 12 weeks due to intolerance (n~20). HCV patients who are either ineligible for or intolerant to alfa/RBV represent a significant unmet medical need, as there are no effective treatments available to these patients.

Sentinel Cohort Results

Of the 10 patients enrolled in the study, nine completed 24 weeks of treatment. Rapid and persistent viral suppression was observed in all nine patients, with undetectable viral load achieved by week 8 and sustained through the end of the 24 week post-treatment follow-up period. One patient discontinued the study at Week 2. This patient had a low viral load at the time of study discontinuation (1.8 log₁₀ IU/mL) and as reported by the investigator achieved and maintained an undetectable viral load through 24 weeks of follow-up post-discontinuation. Despite the evidence of baseline viral substitutions in some patients, there was no apparent association between those substitutions and response to treatment in this study.

Serious adverse events occurred in two patients. One patient experienced Grade 3 fever (pyrexia) and one patient developed Grade 4 elevated bilirubin levels (hyperbilirubinemia) that led to study discontinuation at week 2. As reported by the investigator, this patient achieved SVR with normalization of laboratory values upon discontinuation.

The most commonly reported on-treatment adverse events occurring in at least three patients were Grade 1 diarrhea (n=7), headache (n=4) and liver enzyme increases (n=3 ALT and AST). Of the liver enzyme increases, two patients experienced transient Grade 1 elevations and one patient had a Grade 2 elevation that began at week 16 of treatment and resolved within two weeks post-treatment.

About the Study

In this Phase II open-label clinical trial (AI447-017), a sentinel cohort of ten Japanese patients with chronic HCV genotype 1b infection with null response to prior alfa/RBV treatment (HCV RNA ≤ 2 log₁₀ IU/mL at 12 weeks of alfa/RBV therapy) were treated with daclatasvir 60 mg once daily and asunaprevir initially 600 mg twice daily and reduced to 200 mg twice daily, for 24 weeks. The primary efficacy endpoint was the proportion of patients with undetectable viral load (HCV RNA < 15 IU/mL) at 12 weeks post-treatment.

About Bristol-Myers Squibb’s Commitment to Liver Disease

Bristol-Myers Squibb is advancing a portfolio of compounds that aim to address unmet medical needs across the liver disease continuum, including hepatitis C, hepatitis B and liver cancer. The Company’s hepatitis C pipeline includes a portfolio of compounds with different mechanisms of action, pursuing both biologics as well as small molecule antivirals. These compounds are being studied as part of multiple novel treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies. Discovered by Bristol-Myers Squibb through a genomics approach, daclatasvir, also known as BMS-790052, is the first NS5A replication complex inhibitor to be investigated in hepatitis C clinical trials and is currently in Phase III development. Asunaprevir, also known as BMS-650032, is an NS3 protease inhibitor in Phase II development for hepatitis C.

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. An estimated 170 million people worldwide are infected with hepatitis C, with genotype 1 being the most prevalent genotype. Up to 90 percent of those infected with hepatitis C will not clear the virus and will become chronically infected. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to 25 percent may progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a potentially curable disease.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

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 clinical trials of this compound will support a regulatory filing, or that the compound will receive regulatory approval or, if approved, that it will become a commercially successful product. 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, 2010, 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.