Merck Submits New Drug Application in China for Doravirine, an NNRTI for HIV-1 Treatment

By Holly

Today (September 27), the Center for Drug Evaluation (CDE) of the National Medical Products Administration accepted the marketing application for Merck’s HIV drug Doravirine tablets, with the acceptance number JXHS1900114.

Doravirine, developed by Merck Sharp & Dohme (MSD), is one of the active ingredients in Delstrigo and Pifeltro.

Pifeltro (doravirine, 100 mg) is a novel, once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI) that can be used in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults with no evidence of resistance to NNRTIs, either historically or at present.

Delstrigo is a once-daily, oral, fixed-dose, triple-combination tablet composed of doravirine (100 mg), lamivudine (3TC, 300 mg), and tenofovir disoproxil fumarate (TDF, 300 mg).

In August and November 2018, Delstrigo and Pifeltro were approved by the U.S. FDA and the European Union, respectively, for the treatment of adult patients with HIV-1 infection who have no history of antiretroviral therapy.

The approvals of Delstrigo and Pifeltro were based on the results of the pivotal randomized, double-blind, multicenter, active-controlled Phase 3 clinical trials named DRIVE-AHEAD and DRIVE-FORWARD, respectively.

In the DRIVE-AHEAD study, 728 antiretroviral-naïve patients with HIV-1 were enrolled and randomly assigned to receive either Delstrigo or a combination regimen of efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). Delstrigo demonstrated sustained viral suppression over 48 weeks, meeting the primary endpoint of non-inferiority compared to the control group. In the Delstrigo group, 84% of patients achieved HIV-1 RNA levels <50 copies/mL, versus 81% in the control group. Among patients with high baseline viral loads, 77% in the Delstrigo group achieved viral suppression, compared to 74% in the control group.

In the DRIVE-FORWARD trial, 766 antiretroviral-naïve patients were enrolled and randomized to receive either Pifeltro or darunavir plus ritonavir (DRV+r), in combination with emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) or abacavir (ABC)/lamivudine (3TC). Pifeltro met the primary endpoint of the trial, demonstrating non-inferiority compared to the control group. At Week 48 of treatment, 84% of patients in the Pifeltro group achieved HIV-1 RNA levels <50 copies/mL, compared with 80% in the control group. Among patients with high baseline viral load, the proportion achieving viral suppression was 77% in the Pifeltro group versus 74% in the control group.

Human immunodeficiency virus (HIV) has caused more than 35 million deaths worldwide. According to statistics, the annual number of new HIV cases in China in 2017 was three times that of 2010. It is hoped that Delstrigo and Pifeltro will be launched on the market as soon as possible to provide more treatment options for people living with HIV in China.