Panacos Pharmaceuticals this week released results of a phase IIa trial of its HIV maturation inhibitor PA-457, ahead of a late breaker presentation next month at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy in New Orleans.
PA-457 reduces HIV viral load by interfering with the production of the HIV capsid protein. If this protein is not assembled, any HIV particles that are produced will be defective and unable to infect other human cells.
Panacos carried out a ten day double blind study in which participants were randomised to receive either a placebo or PA-457 at one of four doses (25, 50, 100 or 200mg).
According to a company press release, the median viral load change at Day 11 at the 200mg dose was -1.03 log10 copies/ml. Median Day 11 values at the other dose levels were: Placebo: +0.03 log10 copies/ml; 25mg: +0.05 log10 copies/ml; 50mg: -0.17 log10 copies/ml; 100mg: -0.48 log10 copies/ml.
In patients with baseline viral loads under 100,000 copies/ml the median Day 11 reduction was -1.52 log10 at the 200mg dose level (three of six patients) and -0.56 log10 at the 100mg dose level (five of six patients). These results compare favourably at the higher doses with responses to T-20 (enfuvirtide) and to maraviroc (a CCR5 antagonist), each developed to target a new stage in the HIV life cycle and therefore unlikely to be affected by cross-resistance among treatment-experienced patients.
Genetic analysis of HIV in patients pre- and post- treatment, available now for 21 out of 33 patients in the study, showed no evidence of the development of resistance to PA-457, the same result as seen previously in a single dose study with PA-457.
Graham P. Allaway Ph.D., Chief Operating Officer of Panacos, said: "This study indicates that PA-457 has potent anti-HIV activity, providing further clinical proof of principle for this new class of antiretroviral drugs. The overall viral load reduction at the 200mg dose of over 1 log10 strongly supports further development of PA-457. The 1.5 log10 viral load reduction seen in patients at the 200mg dose with less than 100,000 viral copies/ml may potentially reflect the potency of the drug when used in combination therapy in normal clinical practice."