New HIV Drug, BMS-986001, Safe and Effective in Treatment-Naive Patients

BMS-986001, a novel thymidine analog NRTI (nucleoside reverse transcriptase inhibitor) being developed by Oncolys BioPharma, when combined with efavirenz (Sustiva, Stocrin) and lamivudine (3TC, Epivir), was found to have comparable efficacy to tenofovir (Viread) in treatment-naive patients living with HIV, according to phase-2b study results presented by Samir K. Gupta, M.D., M.S., at ICAAC 2014 in Washington, D.C.

Because current NRTIs are associated with toxicities, the researchers expressed a need for new NRTIs that offer improved long-term safety and tolerability, potent antiretroviral activity and limited cross-resistance to existing NRTIs. Therefore, BMS-986001 was specifically designed to better target viral transcription, while minimizing toxicities and adverse events.

The study randomized 297 treatment-naive patients, with CD4 counts over 200 cells/mm3 and viral loads above 5,000 copies/mL, into four treatment groups. Each group received efavirenz and lamivudine with either BMS-986001 (at 100 mg, 200 mg or 400 mg) or tenofovir at 300 mg. The median age of the study participants was 31 years of age and 66% were male.

At week 24, 88% of the 100-mg group, 81% of the 200-mg group, 94% of the 400-mg group and 89% of the tenofovir group achieved a viral load below 50 copies/mL. Only four people (6%) in the 200-mg group and two people (2%) in the tenofovir group discontinued treatment due to an adverse event or death.

At week 48, 75% of the 100-mg group, 81% of the 200-mg group, 89% of the 400-mg group and 82% of the tenofovir group sustained a viral load below 50 copies/mL. In total, five people (7%) in the 200-mg group, two people (3%) in the 400-mg group and four people (4%) in the tenofovir group discontinued treatment due to an adverse event or death.

Overall, a higher percentage of participants in the BMS-986001 groups developed drug resistance (6% - 14%) compared to the tenofovir group (1%). Additionally, BMS-986001 was generally well tolerated through 48 weeks.

The findings support the further development of BMS-986001 as a next-generation thymidine analog NRTI. But they also raise a question: Amidst the rise of extremely effective integrase inhibitors and the proliferation of excellent first-line HIV treatment options, is there still a place for new NRTIs in the medicine chest of the future?

"I think for the next, at least five to 10 years, you are still going to see most people use NRTIs in addition to integrase [inhibitors], probably, as first line," said Grace McComsey, M.D., a professor of pediatrics and medicine at the Case Western Reserve University School of Medicine, in Cleveland, Ohio. McComsey presented a poster on the bone and metabolic safety data of BMS-986001 at ICAAC.

"I think people are concerned now about tenofovir, from renal and bone perspectives; they also worry a little bit about abacavir [Ziagen] and cardiovascular risk, even though the debate continues on this one," McComsey added. "Providers want the perfect NRTI -- that's one without the renal or cardiovascular toxicity -- so they can add it to dolutegravir [Tivicay, DTG] or other potent drugs."

Oncolys was originally partnered with Bristol-Myers Squibb (BMS) to develop BMS-986001, however, BMS terminated their agreement, so it remains to be seen what the future of the drug will be.