FDA Approves Pair of HIV-1 Once-Daily Combination Therapies from Merck

The US Food and Drug Administration (FDA) has approved a pair of Merck therapies indicated to treat HIV-1 infection in adult patients with no prior antiretroviral treatment (ART) experience.

Once-daily fixed-dose combination tablet doravirine (100 mg), lamivudine (3TC, 300 mg), and tenofovir disoproxil fumarate (TDF, 300 mg) (DELSTRIGO), and a new non-nucleoside reverse transcriptase inhibitor (NNRTI) administered in combination with other ARTs (PIFELTRO) have been indicated as once-daily oral therapies for adult patients with HIV-1.

The FDA approvals of the 2 therapies are based on the results of pivotal, randomized, multicenter, double-blind active controlled phase 3 trials DRIVE-AHEAD and DRIVE-FORWARD, which evaluated the efficacy and safety of DELSTRIGO and PIFELTRO, respective, in the indicated patient population.

In DRIVE-AHEAD, investigators randomized 728 patients to receive at least 1 dose of DELSTRIGO or efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV 600 mg/FTC 200 mg/TDF 300 mg) once daily. Patients administered DELSTRIGO demonstrated sustained viral suppression through 48 weeks, reporting non-inferior efficacy versus patients administered EFV/FTC/TDF (84% achieved viral suppression of HIV-1 RNA <50 copies/mL vs 81%, respectively). Of the 21% of patients to report high viral load at baseline (HIV-1 RNA >100,000 copies/mL), more treated with DELSTRIGO reported HIV-1 RNA <50 copies/mL at week 48 than the comparative group (77% vs 72%).

In DRIVE-FORWARD, investigators randomized 766 patients to receive at least 1 dose of PIFELTRO once daily or darunavir 800 mg plus ritonavir 100 mg (DRV+r) once daily. Each therapy was administered in combination with emtricitabine (FTC)/TDF or abacavir (ABC)/3TC, as selected by investigators.

Patients administered PIFELTRO reported sustained viral suppression through 48 weeks and reported non-inferior efficacy versus patients on comparative therapy (84% reaching viral suppression of HIV-1 RNA <50 copies/mL vs 80%, respectively). Similarly to the DRIVE-AHEAD results, of the 20% of patients to report high viral load at baseline, 77% treated with PIFELTRO and 74% treated with comparative therapy achieved HIV-1 RNA <50 copies/mL at week 48.

Both therapies can be administered in combination with an array of non-ART agents, according to investigators, and PIFELTRO can also be co-administered with various ART agents as well. They are contraindicated when co-adminsitered with strong cytochrome P450 3A enzyme-inducing therapies; significant decreases in doravirine plasma concentrations are possible, which could then decrease the effectiveness of DELSTRIGO and PIFELTRO.

David Wohl, MD, of the Division of Infectious Diseases at the University of North Carolina Chapel Hill School of Medicine, noted the approvals provide 2 new options for the treatment of HIV-1—a welcome addition to a growing market of therapies.

“As a result of the remarkable strides made in the fight against HIV, clinicians and their patients have the opportunity to work together to identify treatment regimens that may be best for each individual, taking into account other aspects of that person’s health, including other medicines they may be taking,” Wohl said.

George Hanna, MD, vice president and therapeutic area head of infectious disease, Global Clinical Development, Merck Research Laboratories, believes the therapies will offer a “compelling clinical profile for clinicians and people living with HIV.”

“We are thankful to the researchers as well as those living with HIV and their communities for the collaboration that made today’s approval possible,” Hanna said.