VIENNA – Rilpivirine, an investigational non-nucleoside reverse transcriptase inhibitor for treating HIV, matched the efficacy of the benchmark agent in the class, efavirenz, and edged efavirenz for safety in a pair of phase III studies with more than 1,300 patients combined.
The results showed virologic failure to be the only parameter by which rilpivirine fell short of efavirenz, with rilpivirine's rate nearly twice that of efavirenz, Dr. Calvin J. Cohen said at the meeting.
Despite that, rilpivirine “had significant tolerability advantages over efavirenz,” said Dr. Cohen, research director of the Community Research Initiative of New England in Boston. The HIV-infected patients randomized to 25 mg of oral rilpivirine once daily had a lower rate of discontinuations for adverse events; half the rate of grade 2-4 adverse events; and reduced rates of dizziness, rash, abnormal dreams and nightmares, and grade 3 and 4 lipid abnormalities, compared with those randomized to 600 mg of efavirenz once daily.
“These studies provide valuable information on the safety and tolerability of TMC278 [rilpivirine] and specifically its metabolic and CNS side effect profiles,” Dr. Cohen said in a written statement.
The study was sponsored by Tibotec Pharmaceuticals, a subsidiary of Johnson & Johnson that is developing the drug. Tibotec has filed a New Drug Application with the Food and Drug Administration based on the data Dr. Cohen presented.
The Efficacy Comparison in Treatment-Naive HIV-Infected Subjects of TMC278 and EFV (ECHO) study and the TMC278 Against HIV in a Once Daily Regimen vs. Efavirenz (THRIVE) study had very similar results, differing only in the type of treatment added to each of the two study agents.
In ECHO, all patients also received the standard initial combination of tenofovir and emtricitabine. In THRIVE, each participating physician could decide which dual nucleoside reverse transcriptase inhibitors to prescribe. Their choice was tenofovir and emtricitabine in 60% of the THRIVE patients, zidovudine and lamivudine in 30%, and abacavir and lamivudine in 10%. Both trials enrolled treatment-naive patients with a baseline viral load of more than 5,000 copies/mL.
The median age of all patients in both trials was 36 years, and three-quarters were men. About half of the patients had viral loads greater than 100,000 copies/mL, and their average CD4 cell count was roughly 250 cells/mm
The primary end point of both studies was the percentage of patients with an undetectable viral load (fewer than 50 copies/mL) after 48 weeks on treatment. The end point occurred in 84% of the 686 rilpivirine patients and 82% of the 682 patients who got efavirenz, showing rilpivirine's noninferiority. Curves depicting the rate at which patients attained undetectable viral loads during 48 weeks of treatment showed virtually identical kinetics, Dr. Cohen said. Virologic failure occurred in 9% of the rilpivirine patients and 5% of those on efavirenz.
Discontinuation of treatment for an adverse event occurred in 3% of those on rilpivirine and 8% of those on efavirenz. A grade 2-4 adverse event at least possibly related to treatment occurred in 16% of patients on rilpivirine and 31% of those on efavirenz. Neurologic adverse events appeared in 17% of the rilpivirine patients and 38% of those on efavirenz. Dizziness incidence was 8% with rilpivirine and 26% with efavirenz.
Tibotec also announced that it is collaborating with Gilead Sciences in developing a single-pill, once-daily formulation that combines rilpivirine, tenofovir, and emtricitabine.
Dr. Cohen has received research support from, has served on the speakers bureau for, and has been a consultant to Tibotec, Bristol-Myers Squibb, Gilead Sciences (maker of tenofovir and emtricitabine), and Merck. He has also been a consultant to Abbott.