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FDA Approves Two Fixed-Dose HIV Pills
The FDA has given the green light to two fixed-dose pills for the treatment of human immunodeficiency virus (HIV) infection that combine protease inhibitors –– one made by Bristol-Myers Squibb (BMS) and the other by Johnson & Johnson (J&J) –– with a boosting agent produced by Gilead Sciences.
The BMS drug is Evotaz (atazanavir 300 mg and cobicistat 150 mg), which was approved in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.
Evotaz is co-formulated to be one tablet, administered once-daily, combining the protease inhibitor atazanavir, marketed as Reyataz (atazanavir 200 mg/300 mg), and cobicistat, a pharmacokinetic enhancer marketed as Tybost by Gilead Sciences. Evotaz is the only protease inhibitor pharmaco-enhanced by cobicistat that is supported by comparative phase III trial data.
In a randomized, double-blind clinical study, the efficacy and safety of atazanavir 300 mg with cobicistat 150 mg (the components of Evotaz) (n = 344) were compared with that of atazanavir 300 mg with ritonavir 100 mg (n = 348), another pharmacokinetic-enhancing agent, in combination with emtricitabine/tenofovir disoproxil fumarate (TDF) in treatment-naïve adults. The subjects had a baseline estimated creatinine clearance of greater than 70 mL/min, mean baseline plasma HIV-1 RNA of 4.8 log10 copies/mL, and a mean baseline CD4+ cell count of 352 cells/mm.
At 48 weeks, 85% of patients in the atazanavir/cobicistat arm achieved HIV-1 RNA levels of less than 50 copies/mL compared with 87% of patients in the atazanavir/ritonavir arm. Low rates of virologic failure (HIV-1 RNA ≥ 50 copies/mL: 6% of the atazanavir/cobicistat arm and 4% of the atazanavir/ritonavir arm) were observed at 48 weeks, making Evotaz the only protease inhibitor pharmaco-enhanced with cobicistat with virologic failure rates as low as 6%.
In the study, no protease inhibitor resistance was detected through 48 weeks of treatment. No patients developed TDF‐associated resistance, but two patients in the atazanavir/cobicistat arm developed emtricitabine‐associated resistance.
Since the approval of Reyataz (atazanavir), a component of Evotaz, in July 2003, more than 7 million prescriptions have been filled in the U.S. for once-daily administration, with or without ritonavir, as part of an HIV-1 regimen.
The second FDA approval went to J&J’s Prezcobix (darunavir 800 mg/cobicistat 150 mg) tablets, an HIV-1 protease inhibitor combined with a cytochrome P450 3A4 (CYP3A4) inhibitor, which is indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents in treatment-naïve and treatment-experienced adults with no darunavir resistance-associated substitutions (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, or L89V).
Prezcobix is a once-daily, fixed-dose combination tablet containing 800 mg of darunavir, marketed as Prezista in the U.S., and 150 mg of cobicistat, taken orally with other HIV-1 medications and with food.
The FDA’s approval was based on bioequivalence data from the use of a darunavir and cobicistat fixed-dose combination tablet compared with single agents and on the results of a clinical study evaluating the safety and efficacy of cobicistat-boosted darunavir for the treatment of HIV-1 in adults with no darunavir resistance-associated mutations.
The efficacy of Prezcobix is based on findings from clinical trials of darunavir co-administered with ritonavir and from pharmacokinetic trials showing similar exposures of darunavir when boosted with cobicistat compared with darunavir boosted with ritonavir. Two phase III, open-label trials in the darunavir clinical development program, ARTEMIS and ODIN, studied the once-daily use of darunavir co-administered with ritonavir.
Sources: Bristol-Myers Squibb; January 29, 2015; and Johnson & Johnson; January 29, 2015.