The 9th Annual International AIDS Society (IAS) Conference on HIV Science wrapped up this week. The agenda included 1,700 scientific abstracts and dozens of satellite sessions addressing every aspect of HIV research.
Here are the highlights from two of the phase III trial research presented in Paris.
Merck’s doravirine meets primary efficacy endpoint
Results from the DRIVE-AHEAD study, the second of two pivotal Phase III clinical trials evaluating the efficacy and safety of doravirine, Merck’s investigational, non-nucleoside reverse transcriptase inhibitor (NNRTI), for the treatment of HIV-1 infection were presented.
The multicenter, double-blind, randomized, active comparator-controlled clinical trial is evaluating the safety and efficacy of a once-daily, single-tablet, fixed-dose combination containing doravirine 100 mg, lamivudine 300 mg and tenofovir disoproxil fumarate (TDF) 300 mg versus a once-daily, single-tablet, fixed-dose combination containing 600 mg efavirenz (EFV), 200 mg emtricitabine (FTC), and 300 mg TDF in treatment-naïve HIV-1 infected adults.
At 48 weeks of treatment, the investigational NNRTI met its primary efficacy endpoint of non-inferiority based on the proportion of participants achieving levels of HIV-1 RNA less than 50 copies/mL, compared to a fixed-dose combination of EFV/FTC/ TDF in treatment-naïve adults infected with HIV-1.
The fixed dose combination also met its primary safety endpoint. Fewer patients reported events of several pre-specified neuropsychiatric adverse events compared to treatment with EFV/FTC/TDF. Adverse events included dizziness (8.8 percent versus 37.1 percent); sleep disorders and disturbances (12.1 percent versus 25.5 percent); and inability to think clearly or concentrate (4.4 percent versus 8.2 percent).
“Data from DRIVE-AHEAD at 48 weeks show that a fixed-dose combination tablet containing doravirine achieved viral suppression in HIV-1 infected treatment-naïve adults, comparable to a fixed-dose combination containing efavirenz,” said Dr. Kathleen Squires, professor and director of infectious diseases, Thomas Jefferson University, Philadelphia, PA, a study investigator in a press statement. “The results for doravirine are encouraging, as it may offer appropriate patients a new single-tablet treatment option.”
Merck plans to submit New Drug Applications with the FDA in the fourth quarter of 2017.
Gilead’s Bictegravir-Containing Regimen Results
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-naïve adults at the conference.
The ongoing studies found BIC/FTC/TAF to be statistically non-inferior to regimens containing dolutegravir (50mg) (DTG) in combination with a dual-NRTI backbone.
Study 1489 randomized 629 treatment-naïve adults with HIV to receive either the BIC/FTC/TAF combination or a therapy of 600 mg abacavir (ABC), 50 mg dolutegravir (DTG) and 300 mg lamivudine (3TC). At week 48 of treatment, 92.4 percent of patients taking BIC/FTC/TAF and 93 percent of patients taking ABC/DTG/3TC achieved the primary endpoint of HIV-1 RNA levels less than 50 copies/mL.
“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 in a press statement. “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.”
Study 1490 randomize a total of 645 treatment-naïve adults with either BIC/FTC/TAF or DTG+FTC/TAF. At Week 48, 89.4 percent of patients taking BIC/FTC/TAF and 92.9 percent of patients taking DTG+FTC/TAF achieved the primary endpoint of HIV-1 RNA levels less than 50 copies/mL.
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.
Lead author of Study 1490, Paul Sax, MD, clinical director of the division of infectious diseases at Brigham and Women’s Hospital, Boston and professor of medicine at Harvard Medical School, adds that the data reinforces the safety and efficacy profile of the combinations. “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 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.
Filed Under: Drug Discovery