Bristol-Myers Squibb Company presented data from study AI430-003 on BMS-488043, one of the compounds from its series of experimental HIV-1 attachment inhibitors -- a potential new class of antiretrovirals -- at a major medical conference in San Francisco. The study investigated the antiviral activity, safety, and tolerability of BMS-488043 -- a novel, oral small-molecule attachment inhibitor of HIV-1 that blocks viral entry by binding to the viral envelope protein gp120 and preventing it from binding to cellular CD4 receptors. The data demonstrate that the experimental attachment inhibitor compound has antiviral activity in HIV-1 infected patients, achieving proof of concept for this type of HIV inhibitors and warranting further development of BMS-488043 and this series of compounds.
"Bristol-Myers Squibb is particularly excited about this compound, which is one in a series discovered in our own labs," said James Palmer, president, Bristol-Myers Squibb Pharmaceutical Research Institute. "As a leading virology company we are committed to developing innovative, safe and effective medicines that address the needs of patients dealing with this disease. The data is very encouraging and we are looking forward to advancing this compound through further clinical trials."
Inclusion criteria for this Phase IIa study included individuals who did not have a medical indication for antiretroviral therapy (both naive or those off therapy for greater than 16 weeks), had a CD4 cell count of greater than 250 cells/mm3, and a plasma viral load of 5,000 to 500,000 copies/mL. Two groups of 15 HIV-1 infected adults (12 active/three placebo per group) received 800 or 1800 mg doses of BMS-488043 or placebo every 12 hours for seven days and in the morning of day eight with a high-fat meal. Viral load was assessed daily.
Early data show that the majority of BMS-488043-treated patients in both treatment arms (7/12 in the 800 mg arm and 8/12 in the 1800 mg arm) experienced at least a 1.0 log10 copies/mL decline in viral load (with some achieving reductions of up to 2.0 log10 copies/mL). There were three moderate adverse events reported in the study (fatigue, abscess, and diarrhea) and no grade 3-4 lab abnormalities or adverse events and no discontinuations from the study. Eight days of monotherapy with BMS-488043 was generally safe and well- tolerated. The combination of novel mechanism, oral bioavailability, and potent antiviral activity of BMS-488043 warrants further development of this compound and others in the series.