FDA approves Bristol-Myers Squibb’s Evotaz™ (atazanavir and cobicistat) for the treatment of HIV-1 infection in adults

Bristol-Myers Squibb Company (NYSE:BMY) announced today that the U.S. Food and Drug Administration (FDA) has approved Evotaz (atazanavir 300 mg and cobicistat 150 mg) tablets in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. Evotaz is coformulated to be one pill, once-daily, combining the protease inhibitor atazanavir, which is marketed as Reyataz (atazanavir 200 mg/300 mg) capsules, and cobicistat, a pharmacokinetic enhancer marketed by Gilead Sciences, Inc. Today’s approval offers patients living with HIV an innovative treatment option that delivers proven suppression (HIV-1 RNA <50 copies/mL, 85% Evotaz arm; 87% Reyataz/ritonavir arm) through 48 weeks.

The use of Evotaz in patients who have previously received HIV medication should be guided by their baseline resistance to protease inhibitors. Evotaz and Reyataz do not cure HIV-1 infection or AIDS. Evotaz is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the product components and in combination with certain drugs. See Evotaz full contraindications in the Important Safety Information section below.

As a dedicated partner to the HIV community for more than 20 years, Bristol-Myers Squibb continues to discover and develop innovative therapies to meet the needs of a broad range of patients living with HIV. There are approximately 50,000 new cases of HIV each year, with an estimated 1.1 million people living with the condition in the U.S. While many are diagnosed and undergoing treatment, only one quarter are virally suppressed, demonstrating the continued need for additional treatments to help patients achieve viral suppression.

“We are pleased to provide physicians and patients with an important new option to treat HIV; atazanavir with cobicistat delivers sustained efficacy and safety through 48 weeks, as demonstrated through its rigorous clinical development plan, including a head-to-head Phase III trial,” said Murdo Gordon, Head of Worldwide Markets, Bristol-Myers Squibb. “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.” In the Evotaz arm, zero patients developed tenofovir-associated resistance K65R; two patients developed emtricitabine resistance M184V. In the Reyataz /ritonavir arm, zero resistance was observed.

Evotaz is the first and only protease inhibitor pharmacoenhanced by cobicistat that is supported by comparative Phase III trial data (Gilead Sciences, Inc.’s Study 114). The randomized, double-blind clinical trial (N=692) evaluated the efficacy and safety of Reyataz 300 mg with cobicistat 150 mg (the components of Evotaz) (n=344) versus Reyataz 300 mg with ritonavir 100 mg (Reyataz/ritonavir) (n=348), another pharmacokinetic enhancing agent, in combination with emtricitabine/tenofovir disoproxil fumarate in treatment-naive adults. Patients had a baseline estimated CrCL >70mL/min, a 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 Evotaz arm achieved HIV-1 RNA levels of <50 copies/mL compared to 87% of patients in the Reyataz/ritonavir arm. Low rates of virologic failure (HIV-1 RNA ≥50 copies/mL: 6% Evotaz arm; 4% Reyataz/ritonavir arm) were observed at 48 weeks, making Evotaz the only protease inhibitor pharmacoenhanced with cobicistat with virologic failure rates as low as 6%.

In the study, zero protease inhibitor resistance was detected through 48 weeks. No patients developed tenofovir‐associated resistance, and two patients in the Evotaz arm developed emtricitabine‐associated resistance. Various degrees of resistance and cross-resistance have been observed among protease inhibitors; however, resistance to atazanavir may not preclude the use of other protease inhibitors.

“Maintaining sufficient drug concentrations inhibits viral replication and prevents the development of resistance, which are critical considerations in treating patients with HIV,” said study investigator Joel Gallant, associate medical director of Specialty Services at Southwest CARE Center in Santa Fe, New Mexico, and adjunct professor of medicine in the Division of Infectious Diseases at the Johns Hopkins University School of Medicine. “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.”

Evotaz demonstrated a safety profile comparable to Reyataz/ritonavir. The most common moderate to severe adverse events in the Evotaz arm and Reyataz/ritonavir arm were: rash (5%, 4%); jaundice (5%, 3%); ocular iterus (3%, 1%); nausea (2%, 2%). There were similar low rates of discontinuation due to adverse events (AEs) with Evotaz as compared to Reyataz/ritonavir (7% and 7%, respectively).

Additional research confirmed that Evotaz is bioequivalent to the co-administration of its components, Reyataz and cobicistat, when given with a light meal.

In October 2011, Bristol-Myers Squibb announced a licensing agreement with Gilead for the development and commercialization of a once-daily, fixed-dose combination product of atazanavir and cobicistat, now named Evotaz. Under the terms of the agreement, Bristol-Myers Squibb and its affiliates are responsible for the formulation, manufacturing, registration, distribution and commercialization of the Evotaz fixed-dose combination product worldwide. Gilead retains sole rights for the manufacture, development and commercialization of cobicistat as a stand-alone product and for use in combination with other agents.