Gilead Sciences announced results from a Phase 3 study (Study 1089) that evaluated the safety and efficacy of switching virologically suppressed HIV-1 infected adults from regimens containing emtricitabine and tenofovir disoproxil fumarate (F/TDF [Truvada]) vs. regimens containing the investigational emtricitabine and tenofovir alafenamide (F/TAF).
Data at Week 48 showed the F/TAF-based regimens were statistically non-inferior to the F/TDF-based regimens, as measured by the proportion of patients with HIV-1 RNA levels <50 copies/mL. Also, statistically significant improvements in renal and bone laboratory parameters were seen among patients receiving F/TAF-based regimens.
The 96-week, randomized, multi-center, double-blind, active-controlled study randomized a total of 663 patients either to switch to an F/TAF- or continue an F/TDF-based regimen containing a third antiretroviral agent that was originally part of the patient’s pre-existing treatment regimen. The primary endpoint was virologic success at week 48. F/TAF was dosed at either 200mg/10mg or 200mg/25mg based on the third agent.
Researchers observed similar high rates of virologic suppression in both F/TAF-based regimens and F/TDF-based regimens (94.3% vs. 93.0%). Treatment-related serious adverse events were rare in both groups (0.0% vs. 0.3%, respectively). In addition, patients receiving F/TAF-based regimens had improved bone mineral density (BMD) changes from baseline to Week 48 vs. patients receiving F/TDF-based regimens (hip: +1.14% vs. -0.15%; spine: +1.53% vs. -0.21%; P<0.001 for both).
Across multiple renal function tests, statistically significant differences were seen in patients receiving F/TAF-based regimens vs. F/TDF-based regimens, which included median changes in estimated GFR from baseline to Week 48 (+8.4mL/min vs. +2.8mL/min; P<0.001), and median percent changes in urine protein-to-creatinine ratio (-14.6% vs. +7.7%; P<0.001), among others.
TAF is a novel prodrug of tenofovir that has shown high antiviral efficacy comparable to, and at a dose less than, 1/10 that of TDF (Viread). Compared to TDF, TAF has demonstrated improvements in renal and bone safety because TAF enters cells more efficiently than TDF and can be administered at much lower doses.
Gilead filed a New Drug Application (NDA) with the Food and Drug Administration (FDA) for two fixed-dose combinations of F/TAF in April 2015. The Agency has set a target review date of April 7, 2016.
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