Merck's Novel Anti-HIV Drug Doravirine Approved in China

On November 27, the latest public announcement from China’s National Medical Products Administration (NMPA) indicated that the new drug application for doravirine tablets, an antiretroviral therapy for human immunodeficiency virus (HIV) infection developed by Merck Sharp & Dohme (MSD), has been approved. According to earlier disclosures by the NMPA’s Center for Drug Evaluation (CDE), the approved indication is for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adult patients who have no prior or current evidence of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Screenshot source: References

Doravirine is a once-daily oral innovative non-nucleoside reverse transcriptase inhibitor developed by Merck Sharp & Dohme. It binds to the reverse transcriptase of HIV-1, preventing the virus from converting RNA into DNA, thereby blocking HIV-1 replication.

In August 2018, doravirine as a monotherapy and its fixed-dose combination formulations were approved by the U.S. FDA for the treatment of adult patients with HIV-1 infection who had not previously received antiretroviral therapy. This medication can be flexibly combined with other antiretroviral therapies as a single-tablet regimen, or formulated as a fixed-dose combination with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF).

The doravirine monotherapy tablet has been approved for marketing in China, and its marketing application was previously included in the priority review by the CDE. The clinical efficacy of doravirine in anti-HIV infection had already been validated in a pivotal Phase 3 clinical trial named DRIVE-FORWARD.

Source: CDE Official Website

In this study, a total of 766 treatment-naïve patients with HIV-1 infection received doravirine or ritonavir-boosted darunavir (DRV/r). These patients also received other antiretroviral agents as part of their regimen, such as emtricitabine/tenofovir or abacavir/lamivudine.

The results showed that the doravirine group demonstrated sustained viral suppression over 48 weeks, meeting the primary endpoint of non-inferiority compared with the DRV+r control group. In the trial group, 84% of patients achieved HIV-1 RNA levels <50 copies/mL, versus 80% in the control group. Among patients with high baseline viral load (HIV-1 RNA >100,000 copies/mL), the proportion achieving viral suppression was 77% in the trial group versus 74% in the control group.

After 96 weeks of treatment, 73.1% of patients in the experimental group achieved plasma HIV-1 RNA levels below 50 copies/mL (vs. 66%). Among patients with high baseline viral loads, doravirine therapy suppressed viral replication in 65.4% of patients (vs. 65.2%).

In terms of safety, the rate of treatment discontinuation due to adverse events was low in both treatment groups (2% in the experimental group and 3% in the control group). Common clinical adverse reactions in the experimental group included nausea (7%), headache (6%), fatigue (6%), diarrhea (5%), and abdominal pain (5%).

As described in Merck’s earlier press release, the data from the DRIVE-FORWARD study demonstrated the efficacy and safety of doravirine, indicating that it provides an important innovative treatment option for patients with HIV-1 infection.

AIDS is a severe disease caused by HIV infection, once considered an incurable and fatal condition. However, with the establishment of combination antiretroviral therapy (commonly known as "cocktail therapy") in the late 20th century, AIDS has become a manageable chronic disease. Although current treatments cannot completely cure HIV infection, they can significantly reduce viral load in patients, maintain immune function, and prevent the transmission of HIV. Through antiretroviral therapy, people living with AIDS can achieve life expectancy comparable to that of the general population.

References:

[1] National Medical Products Administration Government Service Portal. Retrieved Nov 27, 2020, from https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20201127083905173.html

[2] 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. Retrieved August 30, 2018, from https://www.businesswire.com/news/home/20180830005793/en/FDA-Approves-Merck%E2%80%99s-DELSTRIGO%E2%84%A2-doravirine-lamivudine-tenofovir

[3] Merck Announces Week 96 Data from Pivotal Phase 3 DRIVE-FORWARD Study of Its Investigational HIV Therapy Doravirine. Retrieved July 24, 2018, from https://www.businesswire.com/news/home/20180724005161/en/Merck-Announces-Week-96-Data-Pivotal-Phase

Source: Pharma Outlook

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