A 300mg once-daily oral solution dose of the maturation inhibitor, bevirimat (PA-457), has a potent anti-HIV effect and is well tolerated, according to the results of the product’s latest Phase IIB study released by the drug’s manufacturer, Panacos Pharmaceuticals.
Phase IIB studies are designed to find the optimum safe and effective dose of a drug. The results just released show that the 300mg once-daily dose of bevirimat had a more potent anti-HIV effect than the 250mg.
In late 2006 Panacos announced that a 400mg bevirimat tablet delivered lower than expected plasma concentrations of the drug. The Phase IIb study protocol was therefore revised to investigate oral doses of the drug. Doses of bevirimat will be increased by 50mg per cohort recruited to the study, and the next stage of the Phase IIb study will examine the safety and efficacy of a 350mg dose of the drug. It is expected that the optimum dose of the bevirimat oral solution will be between 300mg – 400mg once-daily.
The latest Phase IIB study involved ten patients with extensive experience of antiretroviral therapy whose current treatment regimen was failing to control their viral load. Eight patients were randomised to receive a once-daily 300mg dose of bevirimat oral solution on top of their failing regimen, the remaining two patients received a placebo in addition to their existing antiretrovirals.
After 14 days, the primary endpoint of the study, the bevirimat-treated patients had a mean reduction in their viral load of 1.02 log10. Six patients had a greater than 0.5 log10 reduction in their viral load, with five having a greater than 1.0 log10 reduction.
There were only minimal changes in viral load in the two patients who received the placebo.
Significantly greater reductions in viral load were seen in patients taking the 300mg bevirimat dose than were observed in patients treated with the 250mg dose in the previous stage of the IIb study (mean viral load reduction, 0.68 log10).
Safety data are encouraging for the 300mg dose, with only two patients experiencing mild side-effects (the results are still blinded, so investigators are unable to say if these patients received bevirimat or the placebo).
Mean trough steady state concentrations of the 300mg dose of bevirimat were 48.4 microgrammes/ml compared to a steady state of 38.3 microgrammes/ml for the 250mg dose. This shows that increasing the dose of the drug mean that more bevirimat reaches plasma to fight HIV.
“We are very pleased with results from the results from the 300mg cohort” said Alan Dunton of Panacos. “These data are consistent with the previously presented model that the clinically relevant dose range would likely be between 350 – 400mg. We look forward to initiating the 350mg cohort as we work to determine the optimal dose or doses of bevirimat to take into pivotal [phase III] clinical trials in 2008.”