Investigational Direct-Acting Antiviral BMS-790052 Plus PEG-IFN Alfa and RBV
Investigational Direct-Acting Antiviral BMS-790052 Plus PEG-Interferon Alfa and Ribavirin Achieved Up to 92% Sustained Virologic Response in Phase II Dose-Ranging Study of Treatment-Naïve Hepatitis C Patients
Adverse event profile of regimen containing BMS-790052 was consistent with that of treatment with PEG-Interferon alfa and ribavirin alone
PRINCETON, N.J.–Bristol-Myers Squibb Company (NYSE: BMY) today announced results from a Phase II clinical trial in which treatment with the investigational direct-acting antiviral (DAA) BMS-790052, an NS5A replication complex inhibitor, in combination with PEG-Interferon alfa and ribavirin (RBV), achieved sustained virologic response 12 weeks post-treatment (SVR12) in up to 92% of treatment-naïve patients chronically infected with hepatitis C (HCV) genotype 1 (10 mg dose arm, n=12). Adverse events and serious adverse events were consistent with those reported in the PEG-Interferon alfa and ribavirin arm and were comparable across all doses of BMS-790052. These data were reported today for the first time in a late-breaker poster session at the International Liver Congress, the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany.
“There currently exists a medical need for new medicines or new combinations of medicines for hepatitis C patients as many hepatitis C patients have limited success on the currently available treatments,” said Stanislas Pol, MD, PhD, Professor of Hepatology at Université Paris V (René Descartes), Paris, France and head of the Hepatology unit at Cochin Hospital, Paris, France. “The results of this study warrant further clinical investigation of adding Bristol-Myers Squibb’s investigational compound BMS-790052 to the current medicines to evaluate its potential to address this unmet treatment need.”
The primary endpoint of the study was the proportion of patients with extended rapid virologic response (eRVR) defined as undetectable viral load (HCV RNA < 10 IU/mL) at both Weeks 4 and 12. BMS-790052 plus PEG-interferon alfa and ribavirin achieved higher rates of SVR12 compared to PEG-interferon alfa and ribavirin alone, across all BMS-790052 treatment groups [BMS-790052: 60 mg: 83% (10/12 patients), 10 mg: 92% (11/12 patients), 3 mg: 42% (5/12 patients); PEG-interferon alfa/RBV: 25% (3/12 patients)].
Adverse events (AEs) and serious adverse events (SAEs) were comparable across study arms and were consistent with the safety profile of PEG-Interferon alfa and ribavirin therapy. Four patients discontinued due to AEs in the BMS-790052 60 mg group for a diverse set of adverse events. All four patients had undetectable viral load at the time of study discontinuation and three of these patients achieved SVR12. No new on-treatment SAEs were reported beyond study week 24.
Grade 3 to 4 adverse events for BMS-790052 treatment groups and placebo were BMS-790052: 60 mg: 33.3%, 10 mg: 25%, 3 mg: 8.3%; PEG-interferon alfa/RBV: 41.7%. Two patients (one receiving 3 mg BMS-790052 and one receiving 60 mg BMS-790052) experienced anemia (hemoglobin <9 g/dL). Erythropoietin use was comparable between BMS-790052 treatment groups (one to three patients per arm) and the placebo treatment group (two patients). The use of filgrastim (G-CSF) in the study groups was: BMS-790052: 60 mg: 0%, 10 mg: 25%, 3 mg: 16.7%; PEG-interferon alfa/RBV: 16.7%. Other adverse events, occurring in at least four patients (33.3%) in any cohort include: fatigue (BMS-790052: 60 mg: 50%,10 mg: 50%, 3 mg: 58.3%; placebo: 75%), neutropenia (BMS-790052: 60 mg: 16.7%,10 mg: 33.3%, 3 mg: 25%; placebo: 41.7%), nausea (BMS-790052: 60 mg: 33.3%,10 mg: 33.3%, 3 mg: 41.7%; placebo: 50%), vomiting (BMS-790052 60 mg: 33.3%, 10 mg: 8.3%, 3 mg: 16.7%; placebo: 0%), and headache (BMS-790052: 60 mg: 25%, 10 mg: 75%, 3 mg: 58.3%; placebo: 25%).
About the Study
This double-blind study randomized 48 treatment-naïve HCV genotype 1-infected patients 1:1:1:1 (n=12/arm) to receive one of three doses of BMS-790052 (3 mg, 10 mg, or 60 mg) or placebo once daily, in combination with PEG-interferon alfa-2a and ribavirin for 48 weeks. The primary endpoint of the study was the proportion of patients with extended rapid virologic response (eRVR) defined as undetectable viral load (HCV RNA < 10 IU/mL) at both Weeks 4 and 12. Primary endpoint data were previously reported at EASL 2010 in Vienna, Austria.
Discovered by Bristol-Myers Squibb through a genomics approach, BMS-790052 is part of a portfolio of investigational compounds that the company is developing for the treatment of hepatitis C. BMS-790052 is the first NS5A replication complex inhibitor to be investigated in HCV clinical trials. BMS-790052 is currently in Phase II development.
About Hepatitis C1
Hepatitis C is a virus that infects the liver and is transmitted through direct contact with blood. An estimated 170 million people worldwide are infected with hepatitis C. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, 20 percent will progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a 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 the compound described in this release will move from exploratory development into full product development, that clinical trials of this compound will support a regulatory filing, or that the compound will receive regulatory approval or 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.
1 World Health Organization. Hepatitis C. Available at: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index1.html. Accessed March 9, 2011.