About the TAF Phase 3 Studies
Study 104 and Study 111 are randomized, double-blind, 96-week clinical trials among treatment-naïve HIV-1 infected adults with viral load greater than or equal to 1,000 copies/mL. In each study, a total of 840 patients will be randomized (1:1) to receive a once-daily tablet containing TAF 10 mg/elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg (n=420) or Stribild (n=420).
The primary endpoint of the studies will be the proportion of patients with viral load < 50 copies/mL at 48 weeks of treatment as determined by the FDA-defined snapshot analysis. Secondary endpoints will include the proportion of patients with viral load < 20 copies/mL and < 200 copies/mL at 48 and 96 weeks of therapy as defined by the FDA snapshot analysis, the proportion of patients with viral load < 50 copies/mL at week 48 as defined by the FDA Time to Loss of Virologic Response (TLOVR) analysis, the proportion of patients with viral load < 50 copies/mL at week 96 as defined by the FDA snapshot and TLOVR analyses, and change from baseline in CD4+ cell count at weeks 48 and 96.
The studies will include patients with impaired renal function, i.e., those patients with an estimated glomerular filtration rate between 50 mL/mn and 90 mL/mn (according to the Cockcroft-Gault formula). Bone mineral density will be assessed for all patients by DEXA scans at baseline and every 24 weeks. After week 96, patients will continue to take their blinded study drug until treatment assignments have been unblinded, at which point all will be given the option to participate in an open-label rollover extension and receive the TAF-based single tablet regimen.
About Tenofovir Alafenamide
Tenofovir alafenamide (TAF) is a nucleotide reverse transcriptase inhibitor (NtRTI). It is a novel prodrug of tenofovir, the active agent in Viread
(tenofovir disoproxil fumarate), which is also an NtRTI. Phase 1b dose-ranging studies identified a dose of TAF that is ten times lower than Viread and provides greater antiviral efficacy. The smaller milligram size of TAF may enable the development of new fixed-dose combinations and single tablet regimens for HIV therapy that are not feasible with Viread.
Elvitegravir is a member of the integrase inhibitor class of antiretroviral compounds. Integrase inhibitors interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells. Elvitegravir was licensed by Gilead from Japan Tobacco Inc. (JT) in March 2005. Under the terms of Gilead’s agreement with JT, Gilead has exclusive rights to develop and commercialize elvitegravir in all countries of the world, excluding Japan, where JT retains rights. Gilead submitted a New Drug Application (NDA) to FDA for elvitegravir as a standalone agent on June 27, 2012, and the agency has set a target action date under the Prescription Drug User Fee Act (PDUFA) of April 27, 2013.