New Maturation Inhibitor BMS-176 Shows Potent Control of HIV in Small Study
July 21, 2015
An oral presentation at the 2015 International AIDS Conference in Vancouver this week reported promising results from an early 28-day, Phase IIa study of a new maturation inhibitor called BMS-955176. Maturation inhibitors act at the last step of the HIV life cycle and keep the Gag protein from helping the virus to mature and become infectious. No other drugs of this type have yet made it to market.
During earlier clinical study several years ago, the maturation inhibitor bevirimat was vulnerable to pre-existing genetic mutations in some strains of the virus, with 30% or more of people who took the drug not responding. Development was stopped, and Bristol-Myers Squibb began engineering a new maturation inhibitor not vulnerable to these mutations. An earlier reported, 10-day mono-therapy study of BMS 176 resulted in profound drops in HIV levels, even in people who had the mutations that caused bevirimat to be ineffective.
In the current study, 28 people were divided into 4 groups: 4 took a standard regimen of tenofovir/emtricitabine (Truvada) + ritonavir-boosted atazanavir (ATZ, Reyataz), while another 32 were randomized (8 each) to take either 40mg BMS 176 with ritonavir-boosted ATZ, or 40mg or 80mg BMS 176 with unboosted ATZ.
All participants were male, and nearly everyone was white race. Everyone had a viral load >5,000 HIV RNA (median levels ranged 10,00030,000 over the 4 groups), and everyone had a CD4 count >200 (median counts ranged 427581 cells over the 4 groups). In this short study phase, participants could either be new to treatment or treatment-experienced.
After 28 days, the median reduction in viral load for the three BMS 176 groups ranged from -1.66 to -2.18 log while it was -2.22 for the Truvada group. The maximum median reduction in viral load was seen in the Truvada group (-2.39) and the 80mg dose BMS 176 group (-2.23 log).
One person in the 80mg dose BMS 176 group had serious adverse events. No one stopped the study due to adverse events or side effects. Lab abnormalities were higher in the boosted ATZ group, including increased bilirubin levels (which can lead to jaundice). The unboosted regimens had lower median change in bilirubin levels.
BMS 176 is currently enrolling a dose-finding Phase IIb study in people new to treatment and will also conduct a Phase IIb study in people who are treatment experienced.
Alan McCord is the director of education for Project Inform.
C Hwang, et al. Safety Second-Generation HIV-1 Maturation Inhibitor BMS-955176: Antiviral Activity and Safety with Atazanavir +/- Ritonavir. IAS 2015. July 1922, 2015.
This article was provided by Project Inform. Visit Project Inform's website to find out more about their activities, publications and services.
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