Bristol-Myers Squibb Company announced the submission of a New Drug Application (NDA) to Japan's Pharmaceutical and Medical Devices Agency seeking the world's first interferon-free and ribavirin-free treatment regimen for patients with chronic hepatitis C. The submission is based on results from a Phase III study demonstrating that the 24-week, all-oral, interferon-free and ribavirin-free regimen of daclatasvir (DCV) and asunaprevir (ASV) achieved an overall sustained virologic response 24 weeks after the end of treatment (SVR(24)) of 84.7% in Japanese patients with chronic hepatitis C (HCV) genotype 1b who were either interferon-ineligible/intolerant (87.4% SVR(24)) or non-responders (null and partial) to interferon-based therapies (80.5% SVR(24)). These Phase III data will lead the Presidential Plenary at the Viral Hepatitis Session on November 5 during the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington D.C. Globally, there are 170 million people who are infected with HCV. Of the 1.2 million people living with HCV in Japan, approximately 70% of these patients have genotype 1b, which has one of the lowest response rates to current treatments.

Further, a significant number of patients with HCV in Japan are over the age of 65, leading to more disease-related complications and a decreased likelihood of tolerating interferon-based therapies, the standard for treating HCV. The regimen used in the Phase III study resulted in low rates of discontinuation (5%) due to adverse events (AEs). In addition, the rate of serious adverse events (SAEs) was low (5.9%) and varied among patients.

Nasopharyngitis was the most common adverse event in the study (30.2%, 67/222). In this open-label, parallel group, Phase III study, interferon- ineligible/intolerant (IN/I) patients (n=135) and interferon/ribavirin non-responder (NR) patients (n=87) received DCV 60 mg once daily plus ASV 100 mg twice daily for 24 weeks. The primary endpoint was the % of patients with a sustained virologic response at 24 weeks after the end of treatment (SVR(24)).

Virologic Response, High rates of SVR24 were achieved in the two studied patient populations - those IN/I patients with limited therapeutic options (87.4%, 118/135) and those NR patients typically associated with low responses to interferon-based therapies (80.5%, 70/87). Patients >= 65 years of age had SVR24 rates similar to those in patients < 65 years and age did not appear to impact response rates. SVR24 rates for those >= 65 years of age were 91.9% (57/62) in the IN/I elderly patient population and 85.2% (23/27) in the NR elderly population.

There was no clinically significant difference in SVR24 by traditionally important baseline factors including gender, age, baseline HCV RNA, cirrhosis, and IL28B genotype. There were low rates of virologic breakthrough and EOT (end of treatment) detectable HCV RNA (17/222 patients (7.7%)), and low rates of relapse (17/205 patients (8.3%)).