SAN FRANCISCO — The traditional pathway to market for new anti-HIV medications is to win approval first for use in treatment-experienced patients who may have developed drug resistance, and perhaps later be considered for first-line therapy.
That may be changing.
“We now have such a robust armamentarium of regimens for our treatment-resistant patients,” Dr. C. Bradley Hare said, that “our pipeline is really looking at first-line therapy, which I think is really a change in how drugs are being developed and how we analyze these drugs.”
He gave three examples in the development pipeline—rilpivirine, elvitegravir, and S/GSK1349572—in a presentation at a meeting on HIV management sponsored by the University of California, San Francisco.
Follow-up data out to 96 weeks in a phase II clinical trial of 368 treatment-naive patients support 48-week data showing equivalent potency between rilpivirine and efavirenz, said Dr. Hare, medical director of the university's HIV/AIDS clinic at San Francisco General Hospital. Patients were randomized to receive 25, 75, or 150 mg/day of rilpivirine or 600 mg/day of efavirenz, along with backbone therapy consisting of two NRTI drugs.
A virologic response was seen in 71%-76% of patients, which was not significantly different between groups. Overall rates of side effects did not differ significantly.
Patients in every group developed prolongations in QTc interval, though less so with the 25-mg/day dose of rilpivirine. That dose has been selected for further study in a phase III clinical trial, Dr. Hare said.
The pattern of emergence of resistant mutations differed for rilpivirine and efavirenz. Tibotec Pharmaceuticals, which is developing rilpivirine, may coformulate the once-a-day drug with tenofovir and emtricitabine into a single, once-daily pill for triple-drug therapy, he said.
Elvitegravir, a second-generation integrase inhibitor, is being developed by Gilead Sciences. Because preliminary laboratory data look promising, elvitegravir is also being considered for development as a “quad” pill in combination with GS-9350, tenofovir, and emtricitabine, he said.
S/GSK1349572, which is being developed by GlaxoSmithKline, is another second-generation integrase inhibitor that may be headed to phase II/III clinical trials. Unpublished data from a 10-day trial of various doses or placebo in 30 patients suggested that 50 mg taken once daily reduced HIV RNA levels without need for a booster agent.
Disclosures: Dr. Hare has received funding from or been a consultant, adviser, or speaker for Tibotec (which is developing rilpivirine), Gilead (which is developing elvitegravir and a rilpivirine dual formulation), GlaxoSmithKline, Roche, Merck, Bristol-Myers Squibb, Abbott, Pfizer, and Schering-Plough.