FDA NewsPerspective

FDA approves two, once-daily doravirine treatments for HIV

The FDA has approved Delstrigo and Pifeltro as once-daily oral medications for treating HIV-1 infection in adults with no prior ART experience, Merck announced.

Delstrigo is a fixed-dose combination tablet of doravirine (DOR, 100 mg), lamivudine (3TC, 300 mg) and tenofovir disoproxil fumarate (TDF, 300 mg), and Pifeltro (DOR, 100 mg) is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) to be used in combination with other antiretroviral medications.

“A new HIV medication that is effective and well-tolerated and has a relatively high barrier to resistance and can be coformulated with other HIV medications is to be welcomed,” David Alain Wohl, MD, a professor in the division of infectious disease at the University of North Carolina at Chapel Hill and site leader of the UNC AIDS Clinical Trials Unit at Chapel Hill, told Infectious Disease News. “Doravirine is a nice addition to the non-nucleoside class, and it is active even against virus that is resistant to older agents in this class. The coformulation with TDF and 3TC may allow some people on two or more pills to switch to a single tablet a day.”

The FDA approved the drugs based on findings from two randomized, double-blind, active-controlled phase 3 trials — DRIVE-AHEAD and DRIVE-FORWARD.

According to Merck, 728 treatment-naive patients participated in the DRIVE-AHEAD study, in which they were randomly assigned to receive at least one dose of DOR/3TC/TDF or efavirenz/emtricitabine/tenofovir disoproxil fumarate (EVF 600 mg/FTC 200 mg/TDF 300 mg) once daily. Patients being treated with DOR/3TC/TDF demonstrated sustained viral suppression through week 48 compared with the patients treated with EFV/FTC/TDF, meeting primary endpoint of noninferior efficacy (84% in the DOR/3TC/TDF cohort achieved viral suppression of HIV-1 RNA < 50 copies/mL vs. 81% in the EVC/FTC/TDF cohort).

The rate of discontinuation of treatment was lower for patients in the DOR/3TC/TDF treatment group (3%) compared with the EFV/FTC/TDF treatment cohort (6%), according to Merck.

In the DRIVE-FORWARD trial, 766 patients were randomly assigned to receive at least one dose of DOR 100 mg or darunavir 800 mg plus ritonavir 100 mg (DRV+r) once daily in combination with FTC/TDF or ABC/3TC. Following 48 weeks of treatment, patients taking DOR 100 mg demonstrated sustained viral suppression and the drug met its primary endpoint of noninferior efficacy compared with DVR+r, each in combination with FTC/TDF or ABC/3TC, according to a press release.

“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 in the release. – by Bruce Thiel

Disclosure: Wohl reports having served on advisory boards for Gilead Sciences, Janssen, Merck, and ViiV Healthcare.

The FDA has approved Delstrigo and Pifeltro as once-daily oral medications for treating HIV-1 infection in adults with no prior ART experience, Merck announced.

Delstrigo is a fixed-dose combination tablet of doravirine (DOR, 100 mg), lamivudine (3TC, 300 mg) and tenofovir disoproxil fumarate (TDF, 300 mg), and Pifeltro (DOR, 100 mg) is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) to be used in combination with other antiretroviral medications.

“A new HIV medication that is effective and well-tolerated and has a relatively high barrier to resistance and can be coformulated with other HIV medications is to be welcomed,” David Alain Wohl, MD, a professor in the division of infectious disease at the University of North Carolina at Chapel Hill and site leader of the UNC AIDS Clinical Trials Unit at Chapel Hill, told Infectious Disease News. “Doravirine is a nice addition to the non-nucleoside class, and it is active even against virus that is resistant to older agents in this class. The coformulation with TDF and 3TC may allow some people on two or more pills to switch to a single tablet a day.”

The FDA approved the drugs based on findings from two randomized, double-blind, active-controlled phase 3 trials — DRIVE-AHEAD and DRIVE-FORWARD.

According to Merck, 728 treatment-naive patients participated in the DRIVE-AHEAD study, in which they were randomly assigned to receive at least one dose of DOR/3TC/TDF or efavirenz/emtricitabine/tenofovir disoproxil fumarate (EVF 600 mg/FTC 200 mg/TDF 300 mg) once daily. Patients being treated with DOR/3TC/TDF demonstrated sustained viral suppression through week 48 compared with the patients treated with EFV/FTC/TDF, meeting primary endpoint of noninferior efficacy (84% in the DOR/3TC/TDF cohort achieved viral suppression of HIV-1 RNA < 50 copies/mL vs. 81% in the EVC/FTC/TDF cohort).

The rate of discontinuation of treatment was lower for patients in the DOR/3TC/TDF treatment group (3%) compared with the EFV/FTC/TDF treatment cohort (6%), according to Merck.

In the DRIVE-FORWARD trial, 766 patients were randomly assigned to receive at least one dose of DOR 100 mg or darunavir 800 mg plus ritonavir 100 mg (DRV+r) once daily in combination with FTC/TDF or ABC/3TC. Following 48 weeks of treatment, patients taking DOR 100 mg demonstrated sustained viral suppression and the drug met its primary endpoint of noninferior efficacy compared with DVR+r, each in combination with FTC/TDF or ABC/3TC, according to a press release.

“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 in the release. – by Bruce Thiel

Disclosure: Wohl reports having served on advisory boards for Gilead Sciences, Janssen, Merck, and ViiV Healthcare.

    Perspective
    Paul A. Volberding

    Paul A. Volberding

    The care of our patients has long depended on an expanding array of effective and well-tolerated medications. Having choices among different drug classes and of pills with differing individual component drugs allows us to choose an optimum regimen that is individualized, depending on each patient’s prior treatment history, tolerance for side effects and need to avoid interactions with other chronic medication use.

    The announcement that Merck has received approval of two new drugs — an NNRTI either alone or in a three-drug single tab regimen — is another cause of hope for our patients and welcomed additions to our set of treatment tools. It is definitely more good news.

    • Paul A. Volberding, MD
    • Director, University of California, San Francisco’s AIDS Research Institute
      Co-director of the UCSF-Gladstone Center for AIDS Research
      Infectious Disease News Chief Medical Editor

    Disclosures: Volberding reports being the chair of the Merck Data Monitoring Committee for doravirine.