Phase 2 trial with second generation maturation inhibitor

2017-11-15

GSK3532795 is a second generation maturation inhibitor. Its mode of action is inhibition of protease mediated cleavage between capsid protein p 24 and spacer protein -1 in the Gag polyprotein resulting in immature noninfectious viral particles. A
phase 2a trial was performed in three different parts. In the first part HIV-positive patients with subtype B infection were given 10 days of monotherapy with 5-120 mg once daily or placebo. In the second part of the study 40 or 80 mg of GSK3532795 once daily was given together with boosted or non-boosted atazanavir or “standard of care” (SOC: Atazanavir/r, emtricitabin, tenofovir disoproxil fumarate) for 28 days. In a third part of the study, HIV-positive patients with subtype C infection received 40 or 120 mg once daily for 10 days. In both monotherapy parts of the study a viral load reduction of > 1 log was achieved in all patients who were given 40 mg or more. In the part of the study that compared GSK3532795/atazanavir with SOC similar declines of viral load were observed in both groups. Adverse events were all mild to moderate and the proportion of subjects with adverse events was similar to placebo.

Hwang et al. Clin Infect Dis 2017;65:442-452

Comment: We do have a wide range of effective antiretrovirals available already. Nevertheless, it is still valuable that new drugs with novel modes of actions with different resistance mechanisms are developed. The development of the first generation maturation inhibitor (beviramat) was stopped as naturally occurring Gag polymorphism resulting in resistance was found to be common. With the second generation maturation inhibitor this obstacle seems to be overcome and continued development
is supported by these phase 2 results.