Two Phase III studies (Studies 1489 and 1490) are positive for the fixed-dose combination of bictegravir (BIC) + emtricitabine/tenofovir alafenamide (FTC/TAF) for the treatment of HIV-1 infection in treatment-na�ve adults.-Gilead Sciences

Gilead Sciences, Inc. announced detailed 48-week results from two Phase III studies (Studies 1489 and 1490) evaluating the efficacy and safety of a fixed-dose combination of bictegravir (50 mg) (BIC), a novel investigational integrase strand transfer inhibitor (INSTI), and emtricitabine/tenofovir alafenamide (200/25mg) (FTC/TAF), a dual-NRTI backbone, for the treatment of HIV-1 infection in treatment-naïve adults. In the ongoing studies, BIC/FTC/TAF was found to be statistically non-inferior to regimens containing dolutegravir (50mg) (DTG) in combination with a dual-NRTI backbone from GSK. The data were presented in two late-breaker sessions [MOAB01 and TUPDB02] at the 9th IAS Conference on HIV Science (IAS 2017) in Paris.

In Study 1489 , a total of 629 treatment-naïve adults with HIV were randomized 1:1 to receive BIC/FTC/TAF or abacavir/dolutegravir/lamivudine (600/50/300mg) (ABC/DTG/3TC). At Week 48, 92.4 percent (n=290/314) of patients taking BIC/FTC/TAF and 93.0 percent (n=293/315) of patients taking ABC/DTG/3TC achieved the primary endpoint of HIV-1 RNA levels less than 50 copies/mL (difference: -0.6 percent, 95 percent CI: -4.8 percent to 3.6 percent, p=0.78). A separate analysis investigated the effect of the two regimens on changes in bone mineral density (BMD) and measures of renal function. Mean percentage changes in BMD from baseline to Week 48 were -0.83 percent for BIC/FTC/TAF vs. -0.60 percent for ABC/DTG/3TC (p=0.39) in lumbar spine, and -0.78 percent for BIC/FTC/TAF vs. -1.02 percent for ABC/DTG/3TC (p=0.23) in total hip. No differences were noted between the treatments in changes from baseline to Week 48 for estimated glomerular filtration rate (eGFR) or proteinuria. Lipid changes were not significantly different between the two arms. No patients randomized to either arm developed treatment-emergent resistance and discontinuations due to adverse events were low in both groups (0.0 percent (n=0) for BIC/FTC/TAF vs. 1.3 percent (n=4) for ABC/DTG/3TC). The most commonly reported adverse events (all grades) were nausea (10 percent for BIC/FTC/TAF vs. 23 percent for ABC/DTG/3TC), diarrhea (13 percent vs. 13 percent) and headache (11 percent vs. 14 percent).

In Study 1490 , a total of 645 treatment-naïve adults with HIV were randomized 1:1 to receive BIC/FTC/TAF or DTG+FTC/TAF. At Week 48, 89.4 percent (n=286/320) of patients taking BIC/FTC/TAF and 92.9 percent (n=302/325) of patients taking DTG+FTC/TAF achieved the primary endpoint of HIV-1 RNA levels less than 50 copies/mL (difference: -3.5 percent, 95 percent CI: -7.9 percent to 1.0 percent, p=0.12). No patients in either treatment arm developed resistance to any of the study drugs. Lipid changes were not significantly different between the two arms, and there were no renal discontinuations or cases of proximal renal tubulopathy. Discontinuations due to adverse events were low in both treatment arms (1.6 percent (n=5) for BIC/FTC/TAF vs. <1.0 percent (n=1) for DTG+FTC/TAF). The most commonly reported adverse events (all grades) were headache (13 percent for BIC/FTC/TAF vs. 12 percent for DTG+FTC/TAF) and diarrhea (12 percent vs. 12 percent.

In addition to Studies 1489 and 1490, 48-week data from two other ongoing studies evaluating BIC/FTC/TAF among virologically suppressed adult patients (Studies 1844 and 1878) are also part of the regulatory submissions in the U.S. and EU..