Date: 2015-09-02
Type of information: Results
phase: 3
Announcement: results
Company: Gilead (USA - CA)
Product: fixed-dose combination of emtricitabine and tenofovir alafenamide (200/10 mg and 200/25 mg)
Action
mechanism: nucleoside reverse transcriptase inhibitor/nucleotide reverse transcriptase inhibitor (NRTI). Emtricitabine and tenofovir alafenamide (TAF) are nucleotide reverse transcriptase inhibitor (NRTI). Emtricitabine is an analog of cytidine. TAF has demonstrated high antiviral efficacy at a dose less than one-tenth that of Gilead\'s Viread® (tenofovir disoproxil fumarate, TDF), as well as improved renal and bone laboratory parameters as compared to TDF in clinical trials.
Disease: HIV-1 infection
Therapeutic area: Infectious diseases
Country:
Trial
details: The Phase 3 study is a randomized, double-blind clinical trial among 663 virologically suppressed adults (HIV-1 RNA levels < 50 copies/mL) on a stable regimen containing Truvada for = six consecutive months. Patients were randomized 1:1 to either maintain their Truvada-based regimen (Truvada + placebo + third agent) or switch to an F/TAF-based regimen (F/TAF + placebo + third agent). The study will follow patients for 96 weeks after randomization. The daily dose of F/TAF in the trial was 200/25 mg; if used in combination with a protease inhibitor administered with either ritonavir or cobicistat, the daily dose was 200/10 mg.
The study is ongoing. The primary objective is to evaluate the efficacy of switching FTC/TDF to F/TAF versus maintaining FTC/TDF in HIV-1 positive subjects who are virologically suppressed on regimens containing FTC/TDF as determined by the proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the FDA snapshot analysis. The secondary objectives are to evaluate the renal safety of the two regimens including estimated glomerular filtration rate (eGFR), and to evaluate the bone safety of the two regimens in hip and spine bone mineral density (BMD) at Week 48 and Week 96.
Latest
news: * On September 2, 2015, Gilead Sciences announced that a Phase 3 study evaluating its investigational fixed-dose combination of emtricitabine and tenofovir alafenamide (200/10 mg and 200/25 mg) (F/TAF) for the treatment of HIV-1 infection met its primary objective. The ongoing study was designed to explore the efficacy and safety of F/TAF-based regimens among virologically suppressed adult patients switching from HIV treatment regimens containing emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) (Truvada®). At Week 48, the F/TAF-based regimens and the TDF-based regimens achieved similar rates of virologic suppression based on the proportion of patients with HIV RNA levels (viral load) of less than 50 copies/mL (94.3 percent for F/TAF-based regimens versus 93.0 percent for TDF-based regimens; difference in percentages: 1.3 percent, 95 percent CI: -2.5 percent to 5.1 percent).
Compared to the TDF-based regimens, the F/TAF-based regimens demonstrated statistically significant differences in mean bone mineral density (BMD) at the hip and spine (p<0.001) and in the median change in estimated glomerular filtration rate (eGFR) (p<0.001). General safety and discontinuation rates due to adverse events were comparable between the two arms. The most commonly reported adverse events included upper respiratory tract infection, diarrhea, nasopharyngitis, headache and bronchitis. Both regimens were generally well tolerated. Gilead plans to submit these data for presentation at a scientific conference in 2016.
In April 2015 , Gilead filed a New Drug Application (NDA) with the FDA for two fixed-dose combinations of F/TAF (200/10 mg and 200/25 mg), and the FDA has set a target review date under the Prescription Drug User Fee Act of April 7, 2016 . A Marketing Authorization Application (MAA) in the European Union for F/TAF was fully validated on May 28, 2015 .
