Bristol-Myers Squibb Submits NDAs for 2 Hepatitis C Medications

Bristol-Myers Squibb submitted NDAs for daclatasvir and asunaprevir. Although asunaprevir is limited to treatment of genotype-1 HCV, a combination of daclatasvir with sofosbuvir may be useful in a range of HCV genotypes.

On April 7, 2014, Bristol-Myers Squibb submitted NDAs for 2 hepatitis C medications: the NS5A replication complex inhibitor, daclatasvir (DCV), and the NS3 protease inhibitor, asunaprevir (ASV).¹

The combination of DCV and ASV, both of which are direct-acting orally bioavailable medications, may help treat genotype-1b hepatitis C patients with an interferon-free ribavirin-free regimen. Although trials show an 87.4% rate of sustained viral response after 24 weeks (SVR24) in interferon-ineligible or interferon-intolerant patients with genotype-1b infection, the combination may not be as effective in genotype-1a, -2, or -3 hepatitis C virus (HCV).^1,2

To further boost response rates, Bristol-Myers Squibb scientists are evaluating the 2 products in combination with a third, an investigational medicine codenamed BMS-791325. The 3-agent regimen, which is currently under evaluation in the phase-3 UNITY trials, may improve the efficacy of the DCV/ASV combination, although the UNITY trials are limited to patients with genotype-1 HCV.^3-5

To expand beyond genotype-1 HCV treatment, Bristol-Myers Squibb scientists are evaluating the combination of DCV and Gilead’s sofosbuvir in patients coinfected with HIV and HCV, in patients who are undergoing liver transplants, and in patients with genotype-3 HCV infection. Results of earlier trials with the DCV/sofosbuvir combination, printed in a January 2014 edition of the New England Journal of Medicine, report SVR12 rates among treatment-naïve patients of 98% in genotype-1, 92% in genotype-2, and 89% in genotype-3 HCV infection.^1,6

In a press release, Brian Daniels, MD, senior vice president of Global Development and Medical Affairs at Bristol-Myers Squibb stated, “We are excited to have achieved this milestone and, looking forward, will continue to innovate and invest in daclatasvir in a range of patient types and regimens.”¹

 

References:

• Bristol-Myers Squibb. Bristol-Myers Squibb Submits NDAs for Daclatasvir and Asunaprevir to US FDA for the Treatment of Hepatitis C. http://news.bms.com/press-release/bristol-myers-squibb-submits-ndas-daclatasvir-and-asunaprevir-us-fda-treatment-hepatit. Accessed April 2014.
• Bristol-Myers Squibb. Bristol-Myers Squibb Submits First All-Oral, Interferon-Free and Ribavirin-Free Treatment Regimen for Regulatory Review in Japan for Patients with Chronic Hepatitis C Infection. http://news.bms.com/press-release/bristol-myers-squibb-submits-first-all-oral-interferon-free-and-ribavirin-free-treatme. Accessed April 2014.
• UNITY 1: A Study of an Investigational Treatment Regimen of Daclatasvir (DCV) + Asunaprevir (ASV) + BMS-791325 in a Fixed Dose Combination (the DCV 3DAA (Direct Acting Antiviral) Regimen) for 12 Weeks for the Treatment of Chronic Hepatitis C Virus (HCV) Genotype 1 Infection in Non-cirrhotic Subjects. clinicaltrials.gov/ct2/show/NCT01979939. Accessed April 2014.
• UNITY 2: A Study of an Investigational Treatment Regimen of DCV+ASV+BMS-791325 in a Fixed Dose Combination (the DCV 3DAA (Direct Acting Antiviral) Regimen) With or Without RBV for 12 Weeks for the Treatment of Chronic Hepatitis C Virus (HCV) Genotype 1 Infection in Subjects With Compensated Cirrhosis. clinicaltrials.gov/ct2/show/NCT01973049. Accessed April 2014.
• AASLD 2013: daclatasvir + asunaprevir cures 85% of genotype 1b hepatitis C patients in Japanese study. HIVandHepatitis.com website. www.hivandhepatitis.com/hcv-treatment/experimental-hcv-drugs/4404-aasld-2013-daclatasvir-asunaprevir-cures-85-of-genotype-1b-hepatitis-c-patients-in-japanese-study. Accessed April 2014.
• Sulkowski MS, Gardiner DF, Rodriguez-Torres M, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014;370(3):211-221.