Gilead Sciences, Inc.'s Single Tablet HIV Regimen Meets Goals In Two Phase 3 Studies
Published: Sep 25, 2014
September 24, 2014
By Jessica Wilson, BioSpace.com Breaking News Staff
Biopharmaceutical firm Gilead Sciences, Inc. (GILD) today announced that two Phase 3 clinical trials evaluating a once-daily single tablet treatment regimen containing tenofovir alafenamide (TAF) for the treatment of HIV-1 infection in treatment-naïve adults met their primary objectives.
The studies showed that the single tablet regimen comprising elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg and TAF 10 mg (E/C/F/TAF), was as effective as Gilead’s already FDA-approved Stribild regimen, which consists of elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg. In addition, the regimen being tested demonstrated “more favorable renal and bone safety,” as compared to the Stribild regimen, according to a Gilead press release.
“As individuals with HIV are living longer, there is a need for treatments that are not only highly effective, but also offer an improved safety profile,” said Norbert Bischofberger, Gilead’s executive vice president for research and development and chief scientific officer, in a statement. “Based on these Phase 3 results, we believe that the E/C/F/TAF single tablet regimen has the potential to optimize HIV therapy for a wide range of treatment-naïve patients.”
The studies, which are ongoing, are randomized, double-blind, 96-week clinical trials that include 1,744 treatment-naïve HIV-1 infected adults with a viral load greater than or equal to 1,000 copies/mL.
According Foster City, Calif.-based Gilead “the primary efficacy endpoint of the studies is the proportion of patients with viral load < 50 copies/mL at 48 weeks of treatment as determined by the FDA-defined snapshot analysis.” In addition, “secondary endpoints include change from baseline in bone mineral density at the hip and spine at weeks 48, and change from baseline in serum creatinine at weeks 48.”
The key difference between the two regimens, TAF, is a nucleotide reverse transcriptase inhibitor (NtRTI), and is a prodrug of tenofovir, the active agent in Viread, which is composed of tenofovir disoproxil fumarate. The smaller milligram size of TAF could lead to the development of single tablet regimens for HIV therapy not possible with Viread.
A prodrug is, “an inactive or partially active drug that is metabolically changed in the body to an active drug,” as defined in Mosby's Medical Dictionary. Researchers at the Ernest Mario School of Pharmacy of Rutgers have found that “prodrugs can offer many advantages over parent drugs such as increased solubility, enhanced stability, improved bioavailability, reduced side effects, and better selectivity."
Gilead plans to file regulatory applications for E/C/F/TAF in the United States and the European Union in the fourth quarter of 2014. The company will submit data from the studies for presentation to a scientific conference in early 2015.