Gilead Sciences, Inc. announced that a Phase 3 clinical trial (Study 114) of its pharmacoenhancing or “boosting” agent cobicistat, which increases blood levels of certain HIV medicines to allow for one pill once-daily dosing, met its 48-week primary objective of non-inferiority to ritonavir.
The Study 114 primary endpoint analysis indicated that after 48 weeks of treatment, 85 percent of patients taking a regimen of cobicistat-boosted atazanavir (a protease inhibitor) plus Truvada(R) (emtricitabine and tenofovir disoproxil fumarate) achieved HIV RNA (viral load) of less than 50 copies/mL, compared to 87 percent of patients taking ritonavir-boosted atazanavir plus Truvada (95 percent CI for the difference: -7.4 percent to 3.0 percent). The predefined criterion for non-inferiority was a lower bound of a two-sided 95 percent CI of -12 percent. Discontinuation rates due to adverse events were 7.3 percent and 7.2 percent in the cobicistat and ritonavir arms of the study, respectively. Gilead plans to submit these data for presentation to a scientific conference in 2012.
“The majority of today’s protease-based HIV treatment regimens depend on a boosting agent for optimal efficacy,” said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. “These results demonstrate that cobicistat may provide patients taking protease-based regimens with a much-needed alternative boosting agent. We are now working toward a second quarter 2012 U.S. regulatory filing for cobicistat.”
Small increases in serum creatinine (a value used to estimate kidney function) with resulting decreases in estimated creatinine clearance (by Cockroft-Gault) were observed in this study. At 48 weeks, the mean increase from baseline in serum creatinine was 0.14 mg/dL among cobicistat patients and 0.09 mg/dL among ritonavir patients. The increase in serum creatinine with cobicistat occurs within days of drug initiation and is reversible with values returning to baseline within days after cessation of cobicistat. Results from a separate Phase 1 renal study in healthy volunteers indicate that cobicistat does not affect actual glomerular filtration rates (GFR) as assessed by iohexol clearance (a true measure of kidney function).
Date: December 5, 2011
Source: Gilead Sciences