Gilead Sciences has announced detailed 48-week results from a phase 3 study (Study 1878) evaluating the efficacy and safety of switching virologically suppressed HIV-1 infected adult patients from a multi-tablet regimen containing a boosted protease inhibitor (bPI) to a fixed-dose combination of bictegravir (50 mg) (BIC), a novel investigational integrase strand transfer inhibitor (INSTI), and emtricitabine/tenofovir alafenamide (200/25 mg) (FTC/TAF), a dual-NRTI backbone. In the ongoing study, BIC/FTC/TAF was found to be statistically non-inferior to regimens containing bPIs and demonstrated no treatment-emergent resistance at 48 weeks. The data are being presented at IDWeek 2017 in San Diego (Session 228).

“These data demonstrate the potential of BIC/FTC/TAF to match the efficacy of a boosted protease inhibitor regimen while also offering a high barrier to resistance and fewer interactions with other drugs,” said Eric Daar, MD, chief of the division of HIV Medicine at Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and lead author of Study 1878. “The findings, along with data from three other phase 3 studies in both treatment-experienced and treatment-naïve patients, suggest that the investigational regimen of BIC/FTC/TAF may be appropriate for a broad range of people living with HIV.”

In Study 1878, a total of 577 virologically suppressed adults with HIV taking regimens of boosted atazanavir (ATV) or darunavir (DRV) + abacavir/lamivudine (ABC/3TC) or FTC/tenofovir disoproxil fumarate (TDF) were randomized 1:1 to continue their bPI regimen or to switch to open-label coformulated BIC/FTC/TAF once daily. At the primary endpoint of Week 48, switching to BIC/FTC/TAF was non-inferior to continuing on a bPI regimen with 1.7 percent of patients in each group having HIV-1 RNA =50 c/mL (difference: 0.0 percent, 95 percent CI: -2.5 percent to 2.5 percent, p=1.00); the proportion of patients with HIV-1 RNA <50 c/mL was 92.1 percent in the BIC/FTC/TAF arm and 88.9 percent in the bPI arm, according to FDA snapshot algorithm.

No patients in the BIC/FTC/TAF arm developed treatment-emergent resistance, and one participant on DRV/ritonavir + ABC/3TC developed a treatment-emergent NRTI mutation associated with abacavir. No renal adverse events leading to discontinuations or cases of proximal renal tubulopathy occurred with BIC/FTC/TAF. The incidence of grade 3 or 4 adverse events was 4 percent (n=13) for the BIC/FTC/TAF arm versus 6 percent (n=18) for the bPI arm; the incidence of grade 3 or 4 laboratory abnormalities was 16 percent (n=45) for the BIC/FTC/TAF arm versus 29 percent (n=83) for the bPI arm. The most commonly reported adverse events (all grades) in both arms included headache, diarrhea, nasopharyngitis and upper respiratory tract infection.

“The combination of the unboosted integrase inhibitor bictegravir with the FTC/TAF backbone has the potential to further evolve HIV triple therapy with convenient dosing in a single-tablet regimen,” said Norbert W. Bischofberger, PhD, Gilead’s executive vice president, research and development and chief scientific officer. “We look forward to the opportunity to offer patients this next-generation therapy as part of our TAF-based portfolio of treatments for HIV.”
 
Gilead filed a New Drug Application for BIC/FTC/TAF with a Priority Review voucher on June 12, 2017, and the US Food and Drug Administration (FDA) set a target action date of February 12, 2018, under the Prescription Drug User Fee Act. A marketing application for BIC/FTC/TAF is also under review in the European Union and was validated by the European Medicines Agency (EMA) on July 13.

Bictegravir in combination with FTC/TAF as a single-tablet regimen is an investigational treatment that has not been determined to be safe or efficacious and is not approved anywhere globally.