Study will evaluate PSI-7977 and TMC435 with and without ribavirin in prior null responder, genotype 1 patients.
Pharmasset and Tibotec Pharmaceuticals entered an agreement to conduct a Phase II study combining their candidates for the treatment of chronic HCV. The companies will test Pharmasset’s PSI-7977, a nucleotide polymerase inhibitor, along with TMC435, Tibotec’s protease inhibitor.
The Phase II trial will evaluate the potential to achieve sustained virologic response 12 weeks post treatment with an all oral, once-daily, interferon-free treatment regimen. Specifically, the study will assess the safety, pharmacokinetics, and pharmacodynamics of 12 and 24 weeks of PSI-7977 in combination with TMC435 with and without ribavirin in patients chronically infected with HCV genotype 1 who had a prior null response to peginterferon alfa and ribavirin treatment. The study is planned to start in the second half of this year.
“PSI-7977 is now being studied in interferon-free combinations with each of the three leading classes of direct-acting antivirals: Tibotec’s protease inhibitor, Bristol-Myers Squibb’s NS5a inhibitor, and our own nucleotide PSI-938,” remarks Bill Symonds, Pharmasset’s svp of clinical pharmacology and translational medicine.
Pharmasset also anticipates initiating another interferon-free trial with PSI-7977, a guanine nucleotide polymerase inhibitor, in the third calendar quarter of this year. “This advances one of our key goals at Pharmasset: to develop our nucleotide analogs as the backbone of interferon-free HCV therapy.”
PSI-7977 is a prodrug of a uracil nucleotide analog polymerase inhibitor. It has completed a 28-day Phase IIa trial in combination with peg-interferon and ribavirin (Peg-IFN/RBV). It is currently being tested in the Phase II Proton trial, evaluating the drug in combination with peg-IFN/RBV in HCV genotype 1, 2, or 3 patients; and the Atomic trial, which couples PSI-7977 with peg-IFN/RBV in HCV genotypes 1, 4, 5, and 6.
TMC435 was jointly developed by Tibotec and Medivir, while the Phase III program for the drug is being handled by Tibotec. The compound, a CHC protease inhibitor, received fast-track designation today for chronic HCV.
TMC435 is being developed in combination with Peg-IFN/RBV and with direct-acting antiviral agents without peginterferon and with or without ribavirin. Three global Phase III response-guided studies were initiated in early 2011 by Tibotec. Late-stage trials are also ongoing in Japan.