Phase 3 Study Update of Elvitegravir for Treatment-Experienced HIV

Gilead Sciences announced two-year Phase 3 clinical trial results showing that the integrase inhibitor elvitegravir dosed once daily is non-inferior to raltegravir (Isentress; Merck & Co., Inc.) dosed twice daily among treatment-experienced HIV patients.

Study 145 was a randomized (1:1), double-blind, double-dummy, active-controlled Phase 3 clinical trial comparing the efficacy and safety of elvitegravir (n=354) vs. raltegravir (n=358), each administered with a ritonavir (Norvir; Abbott Laboratories)-boosted background regimen. Eligible participants were HIV-infected treatment-experienced patients with HIV RNA (viral load) of ≥1,000 copies/mL and were required to have documented viral resistance and/or at least six months of treatment experience with two or more different classes of antiretrovirals prior to enrollment.

Trial participants received either once-daily elvitegravir (150mg or 85mg) or twice-daily raltegravir (400mg). Patients' background regimens were based on the results of resistance testing and included a fully-active ritonavir-boosted protease inhibitor, and a second agent that was permitted to be a nucleoside or nucleotide reverse transcriptase inhibitor, etravirine (Intelence; Janssen Therapeutics), maraviroc (Selzentry; Pfizer) or enfuvirtide (Fuzeon; Roche Laboratories). Due to known pharmacokinetic interactions, patients randomized to elvitegravir whose background protease inhibitor was either atazanavir (Reyataz; Bristol-Myers Squibb) or lopinavir (Kaletra; Abbott Laboratories) received an 85mg dose of elvitegravir.

In January 2011, Gilead announced that it would extend the blinded, randomized period of Study 145 from the originally planned 48 weeks to 96 weeks in order to obtain longer-term safety and efficacy data. Based on the achievement of the non-inferiority endpoint at 48 weeks, patients continued to receive the regimen to which they were originally randomized in a blinded fashion through 96 weeks.

At 96 weeks of treatment, 48% of elvitegravir patients compared to 45% of raltegravir patients achieved and maintained HIV RNA (viral load) levels <50 copies/mL, based on the FDA Time to Loss of Virologic Response (TLOVR) algorithm (Intent-to-Treat (ITT) population; 95% CI for the difference: -4.6% to +9.9%; predefined criterion for non-inferiority was the lower bound of a two-sided 95% CI of -10%).

At baseline, the median HIV RNA in the elvitegravir and raltegravir arms, respectively, was 4.35 log10 copies/mL and 4.42 log10 copies/mL. Median CD4 cell counts were 227 cells/mm3 and 215 cells/mm3 for the elvitegravir and raltegravir arms, respectively. Mean increases in CD4 cell counts at Week 96 were 205 cells/mm3 for elvitegravir patients and 198 cells/mm3 for raltegravir patients. Virologic failure rates were similar in both arms: 26% for elvitegravir patients and 29% for raltegravir patients. Of those patients randomized, 7% of patients in each arm developed an integrase resistance mutation.

Elvitegravir is a member of the integrase inhibitor class of antiretroviral compounds. Integrase inhibitors interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells.

For more information call (800) GILEAD-5 or visit www.gilead.com.