Bristol-Myers Squibb and Pharmasset are to carry out a proof-of-concept study evaluating their respective investigational drug candidates BMS-790052 and PSI-7977 as oral combination therapy for chronic hepatitis C (HCV). BMS-790052 is BMS’ NS5A replication complex inhibitor. Pharmasset’s PSI-7977 is a nucleotide polymerase inhibitor.
The proof-of-concept study will evaluate whether the once-daily oral therapy with the drug duo, either with or without concomitant ribavirin therapy, can lead to a sustained viral response 24 weeks post-treatment in patients chronically infected with HCV genotypes 1, 2, and 3. The trial is expected to start during the first half of 2011. The partners claim it will be the first cross-company study combining two oral, direct-acting antivirals.
At the start of November BMS reported positive data from an open-label Phase IIa trial evaluating a combination of BMS-790052 with its own NS3 protease inhibitor BMS-650032 in HCV genotype 1 patients who had previously not responded to standard HCV therapy with interferon and ribavirin (pegIFNα/RBV). The study showed that when given alongside pegIFNα/RBV treatment, a combination of BMS-790052/BMS-650032 led to 9/10 patients achieving complete early virologic response (cEVR, defined as undetectable viral load) by week 12.
Pharmasset’s PSI-7977, meanwhile, is a uracil nucleotide analog inhibitor of the NS5B polymerase. The drug is currently undergoing Phase IIb evaluation. In December 2010 Pharmasset announced the start of a Phase IIb interferon-sparing trial evaluating PSI-7977 in combination with ribavirin (RBV), and with either 0, 4, 8, or 12 weeks of pegIFNα, as therapy in treatment-naïve patients infected with HCV genotype 2 or 3.
Just last week the firm separately reported positive data from another Phase IIb study, which showed that combining PSI-7977 with pegIFNα/RBV therapy resulted in potent viral suppression in patients with HCV genotype 2 or 3, over 12 weeks. Pharmasset says it plans to initiate a separate Phase IIb combination study during 2011, to evaluate PSI-7977 in combination with pegIFNα/RBV over 24 weeks. PSI-7977 is separately being evaluated in a 14-day Phase I trial as combination therapy with the firm’s guanine nucleotide analog, PSI-938.