An oral solution of the maturation inhibitor, bevirimat (PA-457), has a potent anti-HIV effect and is tolerable, according to results of a Phase IIB study announced by the drug’s manufacturer, Panacos Pharmaceuticals.
Late last year, the company announced that a 400mg tablet formulation of the investigational drug delivered lower than expected plasma concentrations. The Phase IIB study protocol was therefore revised to involve administration of a 250mg oral solution of the investigational agent. A 200mg oral solution had previously been used in antiretroviral-naïve individuals in a Phase IIA study.
All the patients in the revised Phase IIB study were heavily treatment experienced and taking a regimen of antiretroviral drugs that was failing to control their viral load. The study lasted 14 days. Patients were randomised to receive either a 250mg either a daily oral solution dose of the maturation inhibitor or a placebo. All the patients continued to take their background antiretroviral regimen.
Results showed that the mean steady state trough concentration of bevirimat was 38.3 micrograms/ml, significantly higher than the mean 19.9 micrograms/ml observed with the 400mg tablet formulation.
Mean viral load fell by 0.68 log10 in the bevirimat-treated patients after two weeks of therapy, compared to a mean fall of 0.18 log10 in the placebo recipients, and a mean drop of 0.36 log10 amongst patients who received the 400mg tablet in the earlier study.
“We are pleased to have these data supporting bevirimat’s efficacy in patients failing therapy due to resistance – the initial target population for out first planned [regulatory] submission”, said Panacos chief executive, Alan Dunton.
He added that the results of the revised Phase IIB study confirmed suspicions that the low plasma concentrations observed with the 400mg tablet “were caused by the prototype tablet formulation, and not by bevirimat itself.”
No significant side-effects or safety issues were observed.
The dose of bevirimat will be increased in subsequent Phase IIB studies by 50mg per cohort. Panacos will release data on the anti-HIV activity, pharmacokinetics and safety of these studies as they become available.