Phase 3 Trial Update of Cobicistat as a Boosting Agent in HIV
Gilead Sciences announced full clinical trial results from a pivotal Phase 3 study evaluating cobicistat, a pharmacoenhancing or “boosting” agent for HIV therapy, compared to ritonavir (Norvir; Abbott Laboratories). The study found that an HIV regimen containing a cobicistat-boosted protease inhibitor was non-inferior to a regimen containing a ritonavir-boosted protease inhibitor at 48 weeks of therapy.
Study 114 was a randomized, double-blind Phase 3 clinical trial comparing the efficacy and safety of cobicistat-boosted atazanavir (Reyataz; Bristol-Myers Squibb) vs. ritonavir-boosted atazanavir, each administered with Truvada (emtricitabine and tenofovir disoproxil fumarate; Gilead Sciences, Inc.), over a 192-week period at more than 200 study sites. Eligible participants were HIV-infected treatment-naïve adults with HIV RNA levels ≥5,000 copies/mL. Trial participants were randomized (1:1) to receive a once-daily regimen of cobicistat 150mg, atazanavir 300mg and Truvada (n=344) or ritonavir 100 mg, atazanavir 300 mg and Truvada (n=348).
At 48 weeks, the study found that 85% of patients on the cobicistat-containing regimen compared to 87% of patients on the ritonavir-containing regimen achieved HIV RNA (viral load) levels <50 copies/mL, based on the FDA snapshot algorithm (95% CI for the difference: -7.4% to +3%; predefined criterion for non-inferiority was a lower bound of a two-sided 95% CI of -12%).
At baseline, patients in the cobicistat and ritonavir arms had a median HIV RNA of 4.78 log10 copies/mL and 4.84 log10 copies/mL and mean CD4 cell count of 353 cells/mm3 and 351 cells/mm3, respectively. Mean increases in CD4 cell counts were 213 cells/mm3 for cobicistat patients and 219 cells/mm3 for ritonavir patients at 48 weeks (P=0.67). Virologic failure rates were low in both arms – 6% for patients receiving cobicistat and 4% for those receiving ritonavir. Drug resistance was also low – two patients developed an NRTI resistance mutation in the cobicistat arm, and none in the ritonavir arm.
Cobicistat is a mechanism-based inhibitor of cytochrome P450 3A (CYP3A). Cobicistat is also a component of the Quad once-daily single tablet regimen for HIV, which is currently under U.S. regulatory review for treatment-naïve adult patients.
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