Gilead’s investigational tenofovir alafenamide (TAF)-based single tablet HIV regimen meets 48-week primary objective in two Phase 3 studies
Posted: 24 September 2014 | | No comments yet
Gilead Sciences, Inc. announced that two Phase 3 clinical trials (Studies 104 and 111) evaluating an investigational once-daily single tablet regimen containing tenofovir alafenamide (TAF) for the treatment of HIV-1 infection in treatment-naïve adults met their primary objectives…
Gilead Sciences, Inc. (Nasdaq:GILD) today announced that two Phase 3 clinical trials (Studies 104 and 111) evaluating an investigational once-daily single tablet regimen containing tenofovir alafenamide (TAF) for the treatment of HIV-1 infection in treatment-naïve adults met their primary objectives. The studies demonstrated that the single tablet regimen comprising elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg and TAF 10 mg (E/C/F/TAF), was non-inferior to Gilead’s Stribild® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) based on the proportion of patients with HIV RNA levels (viral load) of less than 50 copies/mL at 48 weeks of therapy. In addition, E/C/F/TAF demonstrated more favorable renal and bone safety compared to Stribild.
“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, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. “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.”
In Study 104, 93.1 percent (n=405/435) of patients taking E/C/F/TAF compared to 92.4 percent (n=399/432), of patients taking Stribild, with 95 percent CI from -2.6% to 4.5%, achieved HIV RNA of less than 50 copies/mL at week 48. In Study 111, 91.6 percent (n=395/431) of E/C/F/TAF patients compared to 88.5 percent (n=385/435) of Stribild patients, with 95 percent CI from -1.0% to 7.1%, achieved HIV RNA of less than 50 copies/mL at week 48. Both regimens were generally well tolerated. Discontinuation rates due to adverse events, safety and resistance profiles were comparable between E/C/F/TAF and Stribild in both studies.
Laboratory abnormalities were generally similar for both regimens, with the exception of renal and bone safety indicators, which favored the TAF-based regimen. There was a statistically significant difference in the median change in estimated glomerular filtration rate (eGFR) from baseline to week 48, favoring the TAF-based regimen (-6.8 mL/min for E/C/F/TAF vs. -10.4 mL/min for Stribild in Study 104 (p<0.001); -5.7 mL/min for E/C/F/TAF vs. -11.9 mL/min for Stribild in Study 111 (p<0.001)). Additionally, patients taking the TAF-based regimen experienced a significantly smaller median percentage decrease from baseline in lumbar spine bone mineral density compared to Stribild patients (-1.19 vs. -2.67 in Study 104 (p<0.001); -1.11 vs. -2.81 in Study 111 (p<0.001)) and in hip bone mineral density (-0.77 vs. -3.24 in Study 104 (p<0.001); -0.74 vs. -2.78 in Study 111 (p<0.001)).
In Study 104, median changes from baseline in total fasting cholesterol, HDL (high-density lipoprotein or “good” cholesterol) and LDL (low-density lipoprotein or “bad” cholesterol) were, respectively, 30, 7 and 15 mg/dL for E/C/F/TAF and 12, 3 and 2 mg/dL for Stribild (total cholesterol, p<0.001; HDL, p<0.001; LDL, p<0.001). In Study 111, median changes from baseline in total cholesterol, HDL and LDL were respectively, 27, 7 and 11 mg/dL for E/C/F/TAF and 14, 4 and 2 mg/dL for Stribild (total cholesterol, p<0.001; HDL, p<0.001; LDL, p<0.001).
Gilead plans to submit data from Studies 104 and 111 for presentation to a scientific conference in early 2015.
Several additional ongoing Phase 3 studies are evaluating E/C/F/TAF among multiple HIV patient populations, including patients who switch to E/C/F/TAF from either a single tablet or multi-pill Truvada-containing regimens, patients with a history of antiviral drug resistance, patients with mild to moderate renal impairment and treatment-naïve HIV-positive adolescents. An additional Phase 3b study, WAVES, is evaluating E/C/F/TAF among HIV-positive women who switched from a multi-pill regimen.
Based on the results of Studies 104 and 111 and data from these additional ongoing studies, Gilead plans to submit regulatory applications for E/C/F/TAF in the United States and European Union in the fourth quarter of 2014.
