Bristol-Myers Squibb (BMY) on Monday announced that the U.S. FDA granted its investigational DCV Dual Regimen (daclatasvir and asunaprevir) Breakthrough Therapy Designation as a combination therapy in the treatment of genotype 1b chronic hepatitis C infection (HCV).
The announcement is a positive for BMY; however, competition in the HCV market will be intense with four major companies vying for market share – Gilead Sciences (GILD), Johnson & Johnson (JNJ), AbbVie (ABBV) and BMY. BMY had sought a partnership with Gilead Sciences (GILD) to create a combination therapy of daclatasvir and GILD’s recently-approved sofosbuvir, but GILD maintained that it wants to keep combination therapies in-house and BMY stopped its partnership pursuit at the end of January.
Breakthrough Therapy Designation is granted to drugs for serious or life-threatening conditions seeking FDA approval. The drugs must demonstrate preliminary clinical evidence of substantial improvement on at least one clinically significant endpoint over available therapy. Breakthrough Therapy designated drugs get the benefits of fast track approval at the U.S. FDA as well as more intensive FDA guidance on an efficient drug development program.
The FDA’s designation is based on data from BMY’s ongoing phase 3 clinical program evaluating the all-oral combination regimen of daclatasvir (DCV), an investigational NS5A replication complex inhibitor, and asunaprevir (ASV), an investigational NS3 protease inhibitor, without ribavirin. These studies have focused primarily on patients who cannot tolerate or do not respond to traditional treatment with interferon.
There are six genotypes of Hep-C, with GT1 being most prevalent. In the National Health and Nutrition Examination Survey (NHANESIII) study done by the Centers for Disease Control (CDC), nearly 74% of infections in the U.S. were classified at GT1. World Health Organization (WHO) estimates of 60% of infections worldwide are GT1. Hepatitis-C genotype 1b accounts for about 30% of GT1 infections in the U.S.; however, it is much more prevalent outside the U.S. accounting for nearly 60% of GT1 in the EU and the vast majority of GT1 infections in Asia.
Much of the new Hep-C drug development has focused on genotype 1a. While genotype 1a and 1b share many characteristics, they respond differently to treatments, with 1a considered to be more treatment resistant.
The inability to partner with GILD on combination therapy may limit BMY’s share of the genotype 1 market in the U.S., but pending approval for BMY’s daclatasvir in Europe may help BMY gain a market share edge over GILD overseas. BMY believes that it will be able to get off-label use for the combination of daclatasvir and sofosbuvir well before GILD is able to get approval for its in-house combination therapy of sofosbuvir-ledipasvir. While the GILD combination may prove more effective for genotype 1, the combination of daclatasvir and sofosbuvir may be more effective in the less prevalent genotype 3 population.
