Janssen Therapeutics has announced the US Food and Drug Administration (FDA) has approved PREZCOBIX™ (darunavir 800mg/cobicistat 150mg) tablets, an HIV-1 protease inhibitor combined with a CYP3A4 inhibitor, for the treatment of human immunodeficiency virus (HIV-1) in combination with other antiretroviral agents for treatment-naive and treatment-experienced adults with no darunavir resistance-associated substitutions.
PREZCOBIX™ is a once-daily, fixed-dose antiretroviral combination tablet containing 800mg of darunavir, marketed as PREZISTA® in the US, and 150mg of cobicistat, a pharmacokinetic enhancer or "boosting" agent, developed and marketed as Tybost® by Gilead Sciences, taken orally with other HIV-1 medications and with food.
"Additional options remain an important medical priority to meet the diverse needs of those living with and managing this disease," said Dr Karen Tashima, professor of medicine in the division of infectious diseases, Brown University, director of HIV clinical studies, Miriam Hospital, and a lead investigator in the GS-US-216-0130 study. "This approval gives physicians the option of a darunavir-based fixed-dose combination tablet to treat adults living with the HIV-1 infection, which can help reduce the number of pills in their overall treatment regimen."
The FDA approval was based on bioequivalence data evaluating the use of a darunavir and cobicistat fixed-dose combination tablet versus single agents (TMC114IFD1003) and 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 (GS-US-216-0130).The efficacy of PREZCOBIX™ is based on efficacy demonstrated in clinical trials of darunavir co-administered with ritonavir and pharmacokinetic trials showing similar exposures of darunavir when boosted with cobicistat compared to darunavir boosted with ritonavir. Two Phase 3 studies in the darunavir clinical development program, ARTEMIS (TMC114-C211) and ODIN (TMC114-C229), studied the once-daily use of darunavir co-administered with ritonavir.
In the GS-US-216-0130 study, which was conducted with darunavir 800mg and cobicistat 150mg administered as single entities in 313 HIV-infected patients, adverse reactions evaluated through Week 24 did not differ substantially from those reported in clinical trials with darunavir co-administered with ritonavir 100mg. During the darunavir clinical development program, where darunavir was co-administered with ritonavir 100mg once or twice daily, the most common adverse reactions (incidence greater than or equal to 5%) of at least moderate intensity (greater than or equal to Grade 2) were diarrhoea, nausea, rash, headache, abdominal pain and vomiting.
Bristol-Myers Squibb has announced that the FDA has approved Evotaz (atazanavir 300 mg and cobicistat 150mg) 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 200mg/300 mg) capsules, and cobicistat, a pharmacokinetic enhancer marketed by Gilead Sciences. Today’s approval offers patients living with HIV an innovative treatment option that delivers proven suppression (HIV-1 RNA70mL/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
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 Centre 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 andReyataz/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.
[link url="http://www.prnewswire.com/news-releases/prezcobix-darunavircobicistat-approved-in-the-us-for-the-treatment-of-adults-living-with-hiv-1-300028193.html"]Janssen Therapeutics release[/link]
[link url="http://www.businesswire.com/news/home/20150129006600/en/U.S.-Food-Drug-Administration-Approves-Bristol-Myers-Squibb%E2%80%99s#.VM9EQ9KUfE2"]Bristol-Myers Squibb release[/link]