The FDA will decide this year whether the once-daily Merck therapies can be marketed as a switch-on drug for patients with suppressed HIV-1.
The US Food and Drug Administration (FDA) has accepted the supplemental New Drug Applications (sNDAs) for doravirine (Pifeltro) and doravirine/lamivudine/tenofovir disoproxil fumarate (Delstrigo) as potential switch-on therapies for HIV-suppressed adult patients.
The Merck therapy applications were granted FDA consideration on Tuesday, supported by the results of the phase 3 DRIVE-SHIFT non-inferior efficacy trial. By their PDUFA date of September 20, doravirine as a combination therapy with other antiretroviral therapies (ART) and doravirine/lamivudine/tenofovir disoproxil fumarate will be considered as a therapy for people with HIV-1 who are switching from a stable ART regimen, and whose virus is suppressed, as defined by their HIV-1 RNA <50 copies/mL.
Pifeltro, a 100 mg, once-daily, non-nucleoside reverse transcriptase inhibitor (NNRTI), and Delstrigo, a once-daily fixed-dose combination tablet of 100 mg doravirine, 3TC/300 mg lamivudine, and TDF/300 mg tenofovir disoproxil fumarate, were first approved by the FDA as therapies for adult patients with HIV-1 previously untreated with ART in August 2018.
The pair were initially approved based on the results of the pivotal, randomized, multicenter, double-blind active controlled phase 3 DRIVE-AHEAD and DRIVE-FORWARD trials. In DRIVE-AHEAD, patients administered Delstrigo once daily reported non-inferior efficacy to patients administered efavirenz/emtricitabine/tenofovir disoproxil fumarate in sustained viral suppression through 48 weeks. A greater rate of patients with high viral load at baseline treated with Delstrigo reported viral suppression (77%) than the comparative group (72%).
In DRIVE-FORWARD, patients administered Pifeltro in combination with either emtricitabine or abacavir once daily reported non-inferior efficacy to patients administered darunavir plus ritonavir with either emtricitabine or abacavir, as well as a similar rate of high-viral load patients to reach suppression at 48 weeks (77% vs 74%).
The pair’s sNDA consideration will be supported by the results of the DRIVE-SHIFT trial, however. The results—presented at IDWeek 2018 in San Francisco, CA—showed the non-inferior efficacy of Delstrigo as a switch-on therapy compared to continued baseline regimen of 2 NRTIs plus a boosted protease inhibitor, boosted elvitegravir, or NNRTI.
Michael Robertson, MD, executive director and section head for HIV and hepatitis C virus (HCV) at Merck Research Laboratories, noted the company’s clinical development program continues to generate “meaningful evidence for Pifeltro and Delstrigo in people living with HIV.”
“We are pleased that the FDA has accepted these supplemental new drug applications,” Robertson said in a statement. “We look forward to continuing our work with the goal of expanding HIV treatment options.”