A hepatitis C virus protease inhibitor has done well in early clinical trials. The oral drug, VX-950, which is being developed by Vertex Pharmaceuticals, achieved significant reductions in hepatitis C viral load when used in combination with pegylated interferon alfa-2a (Pegasys).
Current treatment for hepatitis C virus involves weekly injections with pegylated interferon and daily doses of ribavirin. This treatment is not universally effective and has unpleasant, often intolerable side-effects. Coinfection with hepatitis C is common amongst HIV-positive individuals and the current standard of treatment is less effective in coinfected individuals than in patients who are only infected with hepatitis C.
In the phase Ib study, the combination of VX-950 and Pegasys produced a significant reduction in hepatitis C viral load in the first two days of treatment, and by day 14, 50% of patients provided with the investigational therapy had an undetectable hepatitis C viral load (below 10 copies IU/ml).
The 14-day randomised, blinded, placebo-controlled trial involved 20 individuals with hepatitis C virus genotype 1. This is the commonest and hardest to treat of the hepatitis C genotypes. Patients were randomised to receive VX-950 at a dose of 750mg every eight hours in combination with Pegasys, the same dose of VX-950 alone, or Pegasys alone. On entry to the study, patients had a median hepatitis C viral load of over four million copies IU/ml.
Analysis of preliminary results showed that individuals taking the investigational protease inhibitor with Pegasys had a median fall of 5.5 log10 in their viral load, compared to a median fall of 4 log10 in patients taking VX-950 alone and 1 log10 in individuals randomised to take Pegasys monotherapy.
No serious side-effects were reported and patients taking VX-950 reported only mild adverse events.
Vertex have announced plans for larger phase II clinical trials which will investigate the safety and effectiveness of VX-950 in combination with both Pegasys and ribavirin. The trial will start in the next few months and involve 200 patients.