The approvals of Delstrigo and Pifeltro are based on findings from 2 phase 3 clinical trials.
Officials with the FDA today approved Merck’s doravirine/lamivudine/tenofovir disoproxil fumarate (Delstrigo) tablet and doravirine (Pifeltro) for the treatment of HIV-1, the company announced in a prepared statement.
Both drugs are indicated for oral, once-daily treatment in adult patients with HIV-1 infection who have had no prior antiretroviral treatment experience.
Delstrigo is a once-daily fixed-dose combination tablet of doravirine (100 mg), lamivudine (3TC, 300 mg) and tenofovir disoproxil fumarate (TDF, 300 mg). Pifeltro, a new non-nuceloside reverse transcriptase inhibitor, is to be administered in combination with other antiretroviral medications.
The approvals are based on phase 3 trials DRIVE-AHEAD and DRIVE-FORWARD, which evaluated the efficacy and safety of the 2 treatments, respectively, in adults with HIV-1 who had no antiretroviral treatment history.
In the DRIVE-AHEAD clinical trial, 728 patients were randomized to receive at least 1 dose of either doravirine/3TC/TDF or efavirenz/emtricitabine/TDF (EFV 600 mg/FTC 200 mg/TDF 300 mg) once daily. Patients treated with doravirine/3TC/TDF demonstrated sustained viral suppression through 48 weeks compared with those treated with EFV/FTC/TDF, meeting its primary endpoint.
Additionally, of the 21% of patients with a high viral load at baseline, 77% in the group treated with doravirine/3TC/TDF and 72% in the EFV/FTC/TDF group achieved HIV-1 RNA <50 copies/mL at week 48. Patients treated with doravirine/3TC/TDF also showed statistically significant superior lipid profiles at this time, as measured by changes from baseline in LDL-cholesterol and non-HDL-cholesterol. A statistically significant lower number of patients treated with doravirine/3TC/TDF reported neuropsychiatric adverse events such as dizziness, sleep disorders and disturbances, and altered sensorium.
In the DRIVE-FORWARD study, 766 patients were randomized and received at least 1 dose of either doravirine once daily or darunavir 800 mg plus ritonavir 100 mg (DRV+r),once daily, each in combination with FTC/TDF or abacavir (ABC)/3TC.
According to the results, doravirine-treated patients demonstrated sustained viral suppression through 48 weeks. Of the 20% of patients with a high viral load at baseline, 77% in the doravirine group and 74% in the DRV+r group achieved HIV-1 RNA <50 copies/mL at week 48. Patients treated with doravirine also showed statistically significant lipid profiles at week 48, as well.
Adverse effects reported by doravirine-treated patients in the trial included nausea, headache, fatigue, diarrhea, and abdominal pain.
Both doravirine/3TC/TDF and doravirine can be co-adminstered with a wide range of non-antiretroviral agents, and doravirine may be co-administered with a wide range of antiretroviral agents, according to Merck. Doravirine/3TC/TDF contains a boxed warning regarding post-treatment acute exacerbations of hepatitis B virus infection.
Doravirine/3TC/TDF and doravirine are contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers, as it may result in decreased effectiveness.
Merck anticipates that both drugs will be stocked through wholesalers within 1 month, according to the press release.
FDA Approves Merck’s DELSTRIGO™ (doravirine / lamivudine / tenofovir disoproxil fumarate), a Once-Daily Fixed-Dose Combination Tablet as a Complete Regimen and PIFELTRO™ (doravirine), an NNRTI, Both for the Treatment of HIV-1 in Appropriate Patients [news release]. Merck’s website. https://www.mrknewsroom.com/news-release/research-and-development-news/fda-approves-mercks-delstrigo-doravirine-lamivudine-tenof. Accessed August 30, 2018.