AASLD-Interim results On Daclatasvir (BMS-790052)W-Peg/Riba In naive geno1/4 Hepatitis C Patients

PRINCETON, N.J., Nov 08, 2011 (BUSINESS WIRE) -- --Efficacy and safety profile to be further evaluated in ongoing Phase III development program

Bristol-Myers Squibb Company today announced interim results from a Phase IIb clinical trial (COMMAND-1) of 395 treatment-naive, genotype 1 and 4 hepatitis C infected patients in which two doses of the investigational NS5A replication complex inhibitor daclatasvir (BMS-790052), in combination with peginterferon alfa and ribavirin (alfa/RBV), achieved higher virologic response rates through Week 12 than the alfa/RBV control group, with comparable rates of adverse events. The data were reported at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco.

The primary efficacy endpoint reported in these interim results is the proportion of HCV genotype 1 patients who achieved undetectable viral load (HCV RNA <10 IU/mL) at Weeks 4 and 12 (extended rapid virologic response, or eRVR). Of the 365 patients with HCV genotype 1 in the study, 54% in each of the daclatasvir dose groups (20 mg and 60 mg) achieved eRVR vs. 14% in the control group. The proportion of HCV genotype 1 patients with undetectable viral load at Week 12 was 78% (115/147) and 75% (110/146) in the daclatasvir 20 mg and 60 mg groups, respectively, compared with 43% (31/72) in the control group. Serious adverse events occurred in 7.5% and 7.6% of patients in the daclatasvir 20 mg and 60 mg groups, respectively, and in 6.4% of patients in the control group.

"The majority of patients with hepatitis C have viral genotypes 1 and 4, which are generally less responsive to therapy than other genotypes. There is a real need for more effective treatment options - especially for genotype 4, as no oral direct-acting antivirals are approved to treat this patient population," said Christophe Hezode, MD, Hopital Henri Mondor, Creteil, France. "The interim results from this Phase IIb study of daclatasvir are encouraging for this compound."

Study Results

Of the 365 patients with HCV genotype 1, 54% in each of the daclatasvir dose groups (20 mg:79/147)(60 mg:79/146) and 14% (10/72) in the control group achieved undetectable viral load (HCV RNA <10 IU/mL) at Weeks 4 and 12 (eRVR). The proportion of HCV genotype 1 patients with undetectable viral load at Week 12 (cEVR) was 78% (115/147) and 75% (110/146) in the daclatasvir 20 mg and 60 mg groups, respectively, compared with 43% (31/72) in the control group. At Week 12, the proportion of patients with viral load below the lower limit of quantification (HCV RNA <25 IU/mL) was 84% in each of the daclatasvir dose groups (20 mg:123/147)(60 mg:123/146), compared with 53% (38/72) in the control group.

Of the 30 patients with HCV genotype 4, undetectable viral load at Week 12 was achieved in 58% (7/12) and 100% (12/12) of patients in the daclatasvir 20 mg and 60 mg groups, respectively, compared with 50% (3/6) of patients in the control group.

One death was reported in the daclatasvir 20 mg group and was determined by the study investigator to be unrelated to treatment. Discontinuations due to adverse events were similar across the daclatasvir regimens and alfa/RBV control group, with 3.8% (6/159) of patients in the daclatasvir 20 mg group, 5.1% (8/158) in the daclatasvir 60 mg group and 7.7% (6/78) in the control group discontinuing treatment. Serious adverse events occurred in 7.5% (12/159) and 7.6% (12/158) of patients in the daclatasvir 20 mg and 60 mg groups, respectively, and in 6.4% (5/78) of patients in the control group.

The most commonly reported AEs across all groups were fatigue (daclatasvir 20 mg:55%)(daclatasvir 60 mg:53%)(control:59%) and headache (daclatasvir 20 mg:42%)(daclatasvir 60 mg:41%)(control:44%). Among commonly reported AEs, a greater-than or equal to 10% difference between either dose daclatasvir and placebo was observed with nausea (daclatasvir 20 mg:35%)(daclatasvir 60 mg:33%)(control:23%) and dry skin (daclatasvir 20 mg:29%)(daclatasvir 60 mg:25%)(control:19%).

Anemia is a recognized adverse event associated with alfa/RBV treatment of HCV. Erythropoietin was administered to 5.0% (8/159) and 7.0% (11/158) of patients in the daclatasvir 20 mg and 60 mg groups, respectively, and to 3.8% (3/78) of patients in the control group. The use of filgrastim in the study groups was: daclatasvir 20 mg: 1.3% (2/159), daclatasvir 60 mg: 3.2% (5/158), and control: 0% (0/78).

About the COMMAND-1 Study

This randomized, double-blind, placebo-controlled phase IIb study (AI444-010) is designed to evaluate the efficacy and safety of two doses of daclatasvir in combination with weekly peginterferon-alfa-2a and ribavirin in treatment-naive patients with HCV genotypes 1 and 4, compared with alfa/RBV and placebo. The study enrolled a total of 395 patients -- 365 with HCV genotype 1 and 30 with HCV genotype 4. Patients were randomized 2:2:1 to receive daclatasvir 20 mg once daily (n=159), daclatasvir 60 mg once daily (n=158) or placebo (n=78) with length of therapy dependent on treatment response.

The primary efficacy endpoints of the study are the proportion of genotype 1 patients with undetectable viral load at Weeks 4 and 12 (extended rapid virologic response, or eRVR) and the proportion of genotype 1 patients with undetectable viral load at 24 weeks post-treatment (sustained virologic response, or SVR24). The primary safety endpoint of the study is the frequency of serious adverse events and study discontinuations due to adverse events at Weeks 12 and 24 on treatment and 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.

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. 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.

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