CROI2015: New HIV maturation inhibitor BMS-955176 appears more potent than earlier beviramat

post_croi2015

At the 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, results were presented from a phase 2a study of the new maturation inhibitor, BMS-955176. This “second-generation” drug inhibits HIV in the last steps of its life cycle by preventing it from becoming fully mature before it can infect more immune cells.

The significance of this could mean that this new drug class could benefit people whose first and second regimens fail. BMS-955176 also appears to overcome certain HIV gag mutations that the earlier experimental maturation inhibitor called bevirimat could not.

This randomized, 10-day mono-therapy study assigned 48 people new to treatment to one of six groups of these liquid doses of BMS176: 5, 10, 20, 40, 80 and 120mg once a day. Another group of 12 took a placebo. All had viral loads above 5,000 and median CD4 count was about 500. Average age was 37, all were men, and the great majority were white.

Viral loads decreased by more than -1 log over 10 days of treatment, and the effect maxed out with the 40mg dose. The greatest decreases occurred on the 40mg dose at -1.7 logs. When comparing BMS176 to bevirimat, both similarly suppressed wild-type HIV but BMS176 suppressed HIV with gag mutations that bevirimat couldn’t in much earlier study.

No serious side effects were seen, and no one stopped the study due to side effects. No serious blood work abnormalities were seen. Diarrhea was the most reported side effect in about 10% of the people on BMS-955176. Phase 2b study will start in early 2015.

SOURCE:
C Hwang, et al. “Antiviral Activity/Safety of a Second-Generation HIV-1 Maturation Inhibitor”. 2015 CROI, Seattle, WA.