Corporate news details

Bristol-Myers Squibb Company (NYSE:BMY) today announced Phase III results from the global HALLMARK-Dual study investigating the all-oral, interferon- and ribavirin-free regimen of daclatasvir (DCV), a NS5A inhibitor, and asunaprevir (ASV), a NS3 inhibitor, among genotype 1b hepatitis C virus (HCV) infected patients. Results showed that the 24-week regimen achieved an overall sustained virologic response (a functional cure) 12 weeks after the end of treatment (SVR₁₂) among treatment-naïve (90%), peginterferon/ribavirin non-responder (82%), and peginterferon/ribavirin ineligible/intolerant (82%) patients, including cirrhotic and non-cirrhotic patients (84% and 85%). In the study the DCV+ASV regimen was generally well tolerated. These data will be presented this week at the 49th annual meeting of the European Association for the Study of the Liver (EASL) The International Liver Congress^TM in London, April 9-13.

Globally, there are 170 million people infected with HCV, with genotype 1 being the most prevalent. There are 9 million people infected in Europe, where there is a high prevalence of HCV genotype 1b.

“Not only was the daclatasvir and asunaprevir regimen highly effective among study participants, it was also very well tolerated, even among sicker patients with more advanced liver disease and higher unmet needs,” said lead study investigator Professor Michael P. Manns, director of the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School, Germany. “Despite a rapidly evolving HCV treatment paradigm, physicians and patients remain in need of new all-oral, interferon- and ribavirin-free regimens that have the potential to achieve virologic cure across a broad range of patients, including those with advanced liver disease and cirrhosis.”

These data were part of the company’s recent DCV and ASV new drug application (NDA) submissions to the U.S. Food and Drug Administration (FDA), and helped support the validated marketing authorization application to the European Medicines Agency for the use of DCV in combination with other agents for the treatment of adults with HCV with compensated liver disease, including genotypes 1, 2, 3, and 4. These data are comparable to a similar Phase III study of this regimen in Japanese patients, which led to the submission of a New Drug Application with Japan’s Pharmaceutical and Medical Devices Agency.

“Daclatasvir has unique scientific characteristics that support ongoing research for its use in multiple all-oral HCV regimens,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “In addition to the HALLMARK-Dual study, we are pleased to be presenting data at EASL on our investigational 3DAA fixed-dose-combination, as well as daclatasvir in combination with other HCV compounds.”

Study Design and Results

This Phase III multinational clinical trial involved 116 sites in 18 countries, including countries that have a high prevalence of genotype 1b such as Korea and Taiwan. In the study, treatment-naïve patients (n=205) received DCV 60 mg once daily plus ASV 100 mg twice daily for 12 weeks, and 102 patients received matching placebo for 12 weeks. The DCV+ASV treatment-naïve group continued treatment through week 24; placebo recipients entered another DCV+ASV study. The peginterferon/ribavirin-ineligible/intolerant (n=235) and non-responder patients (n=205) received the same doses of DCV and ASV for 24 weeks. The primary endpoint was the percentage of patients with a sustained virologic response at 12 weeks after the end of treatment (SVR₁₂).

Virologic Response

• 90% of treatment-naïve patients achieved SVR₁₂
• 82% of patients with prior null or partial response to peginterferon/ribavirin (non-responders) achieved SVR₁₂
• 82% of peginterferon/ribavirin ineligible/intolerant patients achieved SVR₁₂
  • Among peginterferon/ribavirin ineligible/intolerant patients, SVR₁₂ was achieved by patients with anemia/neutropenia (91%); depression (80%) and compensated advanced fibrosis/cirrhosis with thrombocytopenia (73%).

Results among Cirrhotic Patients treated with DCV+ASV

• At baseline, 33 treatment-naïve, 63 non-responders, and 111 ineligible/intolerant patients had cirrhosis. Cirrhotic patients made up ~32% of the study population.

• SVR rates were similar in cirrhotic (84%) and non-cirrhotic (85%) patients.

The regimen used in this Phase III study resulted in low rates of discontinuation (1-3%) due to adverse events (AEs). In addition, the rate of serious adverse events (SAEs) was low (5-7%). Headache was the most common AE in the study (24-25%). No deaths occurred, and no clinically meaningful differences were observed in frequencies of SAEs, AEs leading to discontinuation, or grade 3/4 ALT/AST (liver enzymes) elevations in patients with or without cirrhosis. Importantly, all grade 3/4 ALT/AST elevations observed were reversible and resolved off-treatment.

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, up to 20 percent of people with chronic hepatitis C will develop cirrhosis; of those, up to 25 percent may progress to liver cancer.

About Bristol-Myers Squibb’s HCV Portfolio

Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir (DCV), an investigational NS5A replication complex inhibitor that has been studied in more than 5,500 patients as part of multiple direct-acting antiviral (DAA) based combination therapies. DCV has shown a low drug-drug interaction profile, supporting its potential use in multiple treatment regimens and in people with co-morbidities.

Daclatasvir is being investigated in combination with sofosbuvir in high unmet need patients, such as pre- and post-transplant patients, HIV/HCV co-infected patients, and patients with genotype 3, as part of the ongoing Phase III ALLY Program.

In 2014, the U.S. Food and Drug Administration (FDA) granted Bristol-Myers Squibb’s investigational DCV Dual Regimen Breakthrough Therapy Designation for use as a combination therapy in the treatment of genotype 1b HCV infection.

In 2013, Bristol-Myers Squibb’s investigational all-oral 3DAA Regimen (daclatasvir/ asunaprevir/BMS-791325) also received Breakthrough Therapy Designation, which helped to expedite the start of the ongoing Phase III UNITY Program. Study populations include non-cirrhotic naïve, cirrhotic naïve and previously treated patients. The daclatasvir 3DAA regimen is being studied as a fixed-dose-combination treatment with twice daily dosing.

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 these compounds will support regulatory filings, or that DCV or any other compounds mentioned in this release will receive regulatory approval 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, 2013 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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