The US Food and Drug Administration (FDA) has approved two new oral treatments for adults with HIV-1 infection, Pifeltro and Delstrigo, both from Merck & Co, according to a company news release.
Pifeltro contains doravirine (100 mg), a new non-nucleoside reverse transcriptase inhibitor to be given in combination with other antiretroviral medicines. Delstrigo is a once-daily fixed-dose combination of doravirine (100 mg), lamivudine (3TC; 300 mg), and tenofovir disoproxil fumarate (TDF; 300 mg).
Both drugs are indicated for the treatment of HIV-1 infection in adults with no prior antiretroviral treatment history and are taken once daily with or without food.
The FDA approved doravirine on the basis of the phase 3 DRIVE-FORWARD clinical trial, in which 766 patients with no antiretroviral treatment history were randomly assigned to once-daily treatment with doravirine or darunavir 800 mg plus ritonavir 100 mg (DRV+r), each in combination with emtricitabine (FTC)/TDF or abacavir (ABC)/3TC.
Treatment with doravirine led to sustained viral suppression through 48 weeks, meeting its primary endpoint of noninferiority compared with DRV+r, each in combination with FTC/TDF or ABC/3TC.
At week 48, 84% of the doravirine group and 80% of the DRV+r group had plasma HIV-1 RNA of less than 50 copies/mL.
Of the 20% of study participants with a high viral load at baseline (HIV-1 RNA > 100,000 copies/mL), 77% in the doravirine group and 74% in the DRV+r group achieved HIV-1 RNA of less than 50 copies/mL at week 48.
The rate of therapy discontinuation due to adverse events was low in both groups (2% in the doravirine group and 3% in the DRV+r group). Clinical adverse reactions of all grades occurring in at least 5% of participants in the doravirine group included nausea (7%), headache (6%), fatigue (6%), diarrhea (5%), and abdominal pain (5%). No adverse reactions of grade 2 or higher occurred in 2% or more of participants treated with doravirine.
The doravirine/3TC/TDF combination pill was approved on the basis of data from the phase 3 DRIVE-AHEAD trial, in which 728 patients naive to antiretroviral therapy were randomly assigned to once-daily treatment with doravirine/3TC/TDF or efavirenz (EFV)/emtricitabine/tenofovir disoproxil fumarate (EFV 600 mg/FTC 200 mg/TDF 300 mg).
The doravirine/3TC/TDF combination provided sustained viral suppression through 48 weeks, meeting its primary endpoint of noninferiority compared with EFV/FTC/TDF.
At week 48, 84% of the doravirine/3TC/TDF group had plasma HIV-1 RNA of less than 50 copies/mL, as did 81% of the EFV/FTC/TDF group.
Of the 21% of patients with a high viral load at baseline (HIV-1 RNA > 100,000 copies/mL), 77% in the doravirine/3TC/TDF group and 72% in the EFV/FTC/TDF group achieved HIV-1 RNA of less than 50 copies/mL at week 48.
A statistically significantly lower proportion of doravirine-treated patients reported neuropsychiatric adverse events in the three prespecified categories of dizziness (9% vs 37%), sleep disorders and disturbances (12% vs 26%), and altered sensorium (4% vs. 8%).
The rate of discontinuation of treatment due to adverse events was lower with doravirine/3TC/TDF than with EFV/FTC/TDF (3% vs 6%). Clinical adverse reactions of all grades occurring in at least 5% of patients in the doravirine group included dizziness (7%), nausea (5%), and abnormal dreams (5%). No adverse reactions of grade 2 or higher occurred in 2% or more of patients treated with doravirine.
Both of the new drugs "are contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of Delstrigo and Pifeltro. Delstrigo is contraindicated in patients with a previous hypersensitivity reaction to 3TC," the company said in its news 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," David Wohl, MD, from the AIDS Clinical Trials Unit at the University of North Carolina at Chapel Hill, said in the release. "Today's approvals of Delstrigo and Pifeltro provide two new options for the treatment of HIV-1 in appropriate treatment-naive adult patients."
Merck said it anticipates that both drugs will be stocked through wholesalers within 1 month.