Gilead Announces Phase 3 Results for Investigational Fixed-Dose HIV Treatment

Gilead Sciences, Inc. announced detailed 48-week results from two Phase 3 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-na�ve 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. The data were presented in two late-breaker sessions [MOAB01 and TUPDB02] at the 9th IAS Conference on HIV Science (IAS 2017) in Paris.

"Physicians continue to look for treatment regimens with simple, convenient dosing that can sustain virologic suppression with a safety profile that is appropriate for most HIV patients," said Joel Gallant, MD, MPH, Medical Director of Specialty Services at Southwest CARE Center in Santa Fe, N.M. and lead author of Study 1489. "Combinations of an integrase inhibitor plus a dual-NRTI backbone have become a standard of care for initial treatment of HIV. In clinical trials, the investigational regimen of BIC/FTC/TAF has been well tolerated with low rates of discontinuations due to adverse events, a high barrier to resistance and few drug interactions."

"These data reinforce the safety and efficacy profile consistently seen in other trials evaluating regimens based on the FTC/TAF combination," said Paul Sax, MD, Clinical Director of the Division of Infectious Diseases at Brigham and Women's Hospital, Boston, Professor of Medicine at Harvard Medical School and lead author of Study 1490. "These results suggest that the combination of bictegravir with FTC/TAF has the potential to be appropriate for a broad range of HIV patients, including those with mild to moderate renal impairment."

In Study 1489, a total of 629 treatment-na�ve 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-na�ve 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.
"The Phase 3 findings presented at IAS 2017 demonstrate that a single-tablet combination of bictegravir with the FTC/TAF backbone may deliver an important novel triple-therapy HIV treatment," said Norbert W. Bischofberger, PhD, Gilead's Executive Vice President, Research and Development and Chief Scientific Officer. "These data in treatment-na�ve patients, and data from two additional Phase 3 studies in treatment-experienced patients, formed the basis of our regulatory applications in the United States and the European Union."

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.

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.

For more information, visit www.clinicaltrials.gov