The NDA contains data to support approval for daclatasvir in combination with sofosbuvir; would be the first 12-week regimen specifically for the treatment of hepatitis C genotype 3
The application is based on a Phase III clinical trial which tested a 12-week, ribavirin-free regimen and resulted in sustained virologic response (SVR12) in 90% of treatment-naïve and 86% of treatment-experienced genotype 3 HCV patients
PRINCETON, N.J.--Bristol-Myers Squibb Company (NYSE:BMY) announced today that the resubmitted new drug application (NDA) for daclatasvir, an investigational NS5A replication complex inhibitor, has been accepted for review by the U.S. Food and Drug Administration (FDA) for use in combination with sofosbuvir for the treatment of chronic hepatitis C (HCV) genotype 3. The original NDA has been amended to include data from the Phase III ALLY-3 trial, which showed high cure rates for the combination, with sustained virologic response 12 weeks after treatment (SVR12) in 90% of treatment-naïve and 86% of treatment-experienced genotype 3 HCV patients. SVR12 rates were higher (96%) in non-cirrhotic genotype 3 patients, regardless of treatment history. The FDA will now review the submission within a six-month timeframe.
"The daclatasvir-based NDA seeks to address a high-unmet patient need that still exists despite recent hepatitis C treatment advances. Approximately 9-12% of HCV patients in the U.S. have genotype 3. That's thousands of individuals in the U.S. who historically have had limited treatment options requiring at least 24 weeks of treatment," said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. "We also are continuing clinical trials to determine the potential of daclatasvir-based regimens in treating a range of other high unmet-need patients, including those coinfected with HIV, HCV patients with decompensated cirrhosis, and HCV recurrence in post-transplant patients."
Genotype 3 is estimated to affect 54.3 million people worldwide, and is the second most common hepatitis C genotype after genotype 1 (83.4 million). The more aggressive nature of genotype 3 lies in the damage it causes to the liver, as it is associated with progressive disease, increased rates of steatosis and a disproportionately increased risk of hepatocellular carcinoma.
In the ALLY-3 study, the daclatasvir and sofosbuvir combination regimen was well tolerated, with no deaths, treatment-related serious adverse events, or discontinuations due to adverse events. The most frequent side effects (≥5%) were headache (19.7%), fatigue (19.1%), nausea (11.8%), diarrhea (8.6%), insomnia (5.9%), abdominal pain and arthralgia (both 5.3%). Additionally, there were 17 (11.2%) treatment failures, with 16 relapses post-treatment and 1 rebound at the end of treatment. There were no viral breakthroughs in this ribavirin-free regimen.
About ALLY-3: Study Design
This Phase III open-label clinical trial enrolled 152 genotype 3 HCV patients; 101 treatment-naïve patients and 51 treatment-experienced patients in 2 cohorts each received daclatasvir 60 mg and sofosbuvir 400 mg once daily for 12 weeks, with 24 weeks of follow-up. The primary endpoint was SVR12 rates, defined as HCV RNA < LLOQ target detected or not detected at follow-up week 12 in treatment-naïve and treatment-experienced patients.
About Hepatitis C
Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Approximately 170 million people worldwide are infected with hepatitis C, with an estimated 2.7–3.9 million chronically infected in the United States. 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 20 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, a NS5A complex inhibitor, which continues to be investigated in multiple treatment regimens and in people with co-morbidities.
Daclatasvir was approved in Europe in August 2014, and more recently in Brazil in January 2015, for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of chronic hepatitis C virus (HCV) infection in adults. Daclatasvir also is approved in Japan in combination with asunaprevir, a NS3/4A protease inhibitor. The daclatasvir+asunaprevir dual regimen is Japan's first all-oral, interferon- and ribavirin-free treatment regimen for patients with genotype 1 chronic HCV infection, including those with compensated cirrhosis.
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 daclatasvir will receive regulatory approval in the United States, 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, 2014, 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.