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FDA Approves 2 New Boosted Protease Inhibitor Coformulations for HIV

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The U.S. Food and Drug Administration (FDA) this week approved 2 new fixed-dose coformulations of HIV protease inhibitors with a cobicistat booster. Bristol-Myers Squibb's Evotaz contains atazanavir (sold separately as Reyataz) plus cobicistat, while Janssen Therapeutics' Prezcobix contains darunavir (sold separately as Prezista) plus cobicistat.

Both atazanavir and darunavir were previously approved for use with ritonavir (Norvir) as a booster. Gilead Science's cobicistat (known separately as Tybost) is a novel pharmacoenhancer that raises protease inhibitor levels in a similar way -- by interfering with enzymes in the liver that process the drugs -- but unlike ritonavir, it is not itself active against HIV.

Evotaz

Evotaz, which contains 300 mg atazanavir and 150 mg cobicistat, is taken as 1 pill once-daily with food. It is approved for use in combination with other antiretroviral agents for the treatment of HIV in adults and children over age 3 and weighing at least 10 kg. Evotazmay be used for people starting HIV therapy for the first time as well as treatment-experienced patients; the latter group's use should be guided by their baseline protease inhibitor resistance.

"Evotaz is the first and only protease inhibitor pharmacoenhanced by cobicistat that is supported by comparative Phase 3 clinical trial data, according to a Bristol-Myers Squibb press release.

Research has shown that Evotaz works as well as ritonavir-boosted atazanavir for first-line HIV treatment. The Phase 3 Study 114, which enrolled 692 treatment-naive participants, found that 85% of patients taking Evotaz and 87% taking atazanavir/ritonavir (both with tenofovir/emtricitabine) achieved HIV RNA <50 copies/mL at 48 weeks. Viral suppression rates remained similar at 144 weeks, at 72% vs 74%, respectively. No participants with virological failure developed protease inhibitor or tenofovir resistance mutations. Research has also shown that the Evotaz coformulation works as well as atazanavir and cobicistat taken separately.

Evotaz is generally safe and well-tolerated. The most common moderate to severe adverse events in clinical trials were rash, nausea, and the characteristic atazanavir side effects of jaundice and ocular iterus (yellowing of the eyes) due to elevated bilirubin (hyperbilirubinemia). Evotaz can interact with other drugs processed by the CYP3A enzyme.

"We are pleased to provide physicians and patients with an important new option to treat HIV," Murdo Gordon, Bristol-Myers Squibb's head of worldwide markets said in a company press release. "Evotaz increases the possibility of providing HIV suppression by combining reduced pill burden with a low rate of virologic failure (6% Evotaz arm; 4% Reyataz/ritonavir arm) and zero protease inhibitor mutations."

"Maintaining sufficient drug concentrations inhibits viral replication and prevents the development of resistance, which are critical considerations in treating patients with HIV," added Study 114 investigator Joel Gallant from the Southwest CARE Center in Santa Fe. "Pharmacokinetic studies and a large clinical trial have demonstrated that we can expect the same atazanavir drug levels and clinical efficacy from Evotaz as with ritonavir-boosted Reyataz with one less pill."

The Bristol-Myers Squibb press release, including important safety information, contraindications, interactions, and precautions for Evotaz and Reyataz, is available online.

See the Evotaz full prescribing information for further details.

Prezcobix

Prezcobix, which contains 800 mg darunavir and 150 mg cobicistat, is also taken as 1 pill once-daily with food. It is indicated for use in combination with other antiretroviral agents for the treatment of HIV in adults. Prezcobixis approved for both treatment-naive people and treatment-experienced patients with no darunavir resistance-associated substitutions or mutations (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).

There is less head-to-head research to support the effectiveness of Prezcobix; its efficacy is inferred based on the demonstrated effectiveness of ritonavir-boosted darunavir in Phase 3 trials including ARTEMIS and ODIN. A single arm trial (GS-US-216-0130)that enrolled 313 patients showed that darunavir and cobicistat worked as well as darunavir and ritonavir did in prior trials. Research has shown that the Prezcobix coformulation is bioequivalent to darunavir and cobicistat taken as separate drugs.

Prezcobix also appears generally safe and well-tolerated. Adverse events in the single-arm study did not differ substantially from those reported in clinical trials of darunavir/ritonavir. The most common side effects of darunavir/ritonavir in trials were diarrhea, nausea, abdominal pain, vomiting, rash, and headache. Prezcobix can interact with other drugs processed by the CYP3A enzyme.

The full Janssen press release, including important safety information and contraindications for Prezcobix, is available online.

See the Prezcobix full prescribing information for more details. 

1/30/15

Sources

Bristol-Myers Squibb. U.S. Food and Drug Administration Approves Bristol-Myers Squibb’s Evotaz (atazanavir and cobicistat) for the Treatment of HIV-1 Infection in Adults. Press release. January 29, 2015.

Janssen Therapeutics. Prezcobix (darunavir/cobicistat) Approved in the U.S. for the Treatment of Adults Living With HIV-1. Press release. January 29, 2015

R Klein, K Struble, and S Morin, FDA. Approval of Evotaz, containing 300 mg of atazanavir and 150 mg of cobicistat. HIV/AIDS Update. January 29, 2015.

R Klein, K Struble, and S Morin, FDA. Prezcobix tablet containing 800 mg of darunavir and 150 mg of cobicistat approval. HIV/AIDS Update. January 29, 2015.