Bristol-Myers Squibb and Vertex said today they will team up to conduct Phase II studies of a once-daily combination therapy designed to fight hepatitis C by wedding BMS’ investigational NS5A replication complex inhibitor daclatasvir to Vertex' investigational nucleotide analogue hep C virus (HCV) polymerase inhibitor VX-135.
Under a nonexclusive agreement with BMS, Vertex said it plans to conduct two Phase II studies of the combination. The first is an initial study in approximately 20 noncirrhotic, treatment-naïve people with genotype 1 HCV infection, planned for the second quarter.
Pending data from the initial study, Vertex plans to start a subsequent study in about 250 treatment-naïve people infected with genotype 1, 2, or 3 HCV, including those with cirrhosis, in the second half of 2013.
Each of these studies is expected to evaluate safety, tolerability, pharmacokinetics, and viral cure rates (SVR4 and SVR12) of multiple all-oral regimens of VX-135 and daclatasvir dosed once daily, pending regulatory discussions. Financial details were not disclosed.
“These studies with daclatasvir will provide the first opportunity to evaluate VX-135 as part of all-oral regimens in people with multiple hepatitis C genotypes and in people with cirrhosis,” Robert Kauffman, M.D., Ph.D., Vertex senior vp and CMO, said in a statement.
Vertex said it will also conduct co-formulation activities to evaluate the potential for development of a once-daily fixed-dose combination regimen. The agreement does not address further clinical development activities beyond the Phase II studies.
Daclatasvir, also named DCV or BMS-790052, is an NS5A replication complex inhibitor in Phase III development. Studied in more than 4,100 patients to date, daclatasvir is among hep C drug candidates and combinations under development by BMS.
In results presented last November at the American Association for the Study of Liver Diseases congress, BMS said daclatasvir in combination with asunaprevir, an NS3 protease inhibitor, and BMS-791325, an NS5B non-nucleoside polymerase inhibitor, achieved sustained virologic response 12 weeks post-treatment in 94% of treatment-naïve, genotype 1 chronic HCV patients.
Another combination—daclatasvir and asunaprevir alone without interferon or ribavirin—achieved high rates of sustained virologic response 12 weeks post-treatment in patients with genotype 1b HCV who previously had not responded to alfa interferon and ribavirin, BMS said at the conference.
VX-135 is designed to inhibit HCV replication by acting on the NS5B polymerase. In people with genotype 1, treatment with a 200 mg once-daily dose of VX-135 in a 7-day viral kinetic study was well-tolerated, with no discontinuations due to adverse events, and resulted in a 4.54 log10 median reduction from baseline in HCV RNA.
Data from a 7-day viral kinetic study of VX-135 in people with genotypes 2, 3, and 4 were consistent with data observed in people with genotype 1 and have been submitted for presentation at a future medical meeting.
Vertex gained worldwide rights to VX-135, which until Phase II studies was named ALS-2200, through an exclusive licensing agreement signed with Alios BioPharma, in June 2011. The agreement included a research program focusing on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development as they emerge from the research program.