Molnupiravir Could Become the First Authorized COVID-19 Pill

Unpublished, interim phase 3 data show an approximate 50% reduction in hospitalizations and deaths versus placebo. Merck is expediting FDA application for the antiviral drug.

An orally administered antiviral pill showed significant benefit for adults with mild-to-moderate COVID-19 in a phase 3 trial, according to Merck, and its supporting data is now being used in the company’s application for Emergency Use Authorization (EUA) through the US Food and Drug Administration (FDA).

Molnupiravir, invented at Drug Innovations at Emory (DRIVE) and developed by Merck and Ridgeback Biotherapeutics, is an oral ribonucleoside analog that has been shown to inhibit SARS-CoV-2 replication. In previous research, the investigative drug has shown activity in several preclinical models of SARS-CoV-2 response, including prophylaxis, treatment, and prevention of transmission.

But Merck and Ridgeback will be pursuing an indication similar to antivirals granted EUA in the past: for the treatment and prevention of severe outcomes associated with COVID-19. On the basis of guidance from an independent data monitoring committee and the FDA, the companies have stopped recruitment for the phase 3 study due to the positive interim results, and are planning to produce 10 million treatment courses by the end of the year.

Molnupiravir Phase 3 Interim Trial Results

The phase 3 MOVe-OUT trial was a global, randomized, controlled, double-blinded assessment of molnupiravir versus placebo in non-hospitalized adults with mild to moderate COVID-19. Eligible trial participants had ≥1 risk factor associated with poor COVID-19 outcomes and symptom onset within 5 days prior to their randomization.

Investigators sought a primary efficacy outcome of percentage of participants who are hospitalized and/or who have died through 29 days post-randomization.

At the time of non-peer reviewed, unpublished interim data being shared, the Delta, Gamma, and Mu SARS-CoV-2 variants accounted for approximately 80% of the evaluable cases in MOVe-OUT. Global trial recruitment prominently included patients from Latin America (55%), Europe (23%), and Africa (15%).

The most commonly observed severe COVID-19 risk factors in participants included obesity, older age (≥60 years), diabetes mellitus, and heart disease.

Investigators planned to evaluate interim data from 775 MOVe-OUT participants who were enrolled prior to August 5 of this year.

The interim analysis showed molnupiravir reduced patient risk of COVID-19 hospitalization or death by approximately 50%. Just 28 (7.3%) of patients to receive molnupiravir experienced either outcome, versus 53 (14.1%) patients administered placebo (P = .0012). No patients to receive molnupiravir had died through 29 days post-randomization, versus 8 patients to receive placebo.

Based on available viral sequencing data from approximately 40% of trial participants, investigators observed consistent efficacy of the oral antiviral across Gamma, Delta, and Mu variants.

Adverse events occurred in 35% and 40% of all molnupiravir and placebo patients, respectively, with fewer molnupiravir patients reporting trial discontinuation due to an adverse event (1.3%) than placebo patients (3.4%).

The Future for Molnupiravir

Merck entered a procurement agreement with the federal government this year, whereby the company would supply approximately 1.7 million molnupiravir courses to the US upon EUA or approval from the FDA. The company additionally reached non-exclusive voluntary licensing agreements of the agent with generic manufacturers, for the accelerated availability of the molecule in low- and middle-income companies.

Phase 3 assessments for molnupiravir as a post-exposure prophylactic drug for COVID-19 patients in their household are underway.

The availability of an oral antiviral therapy, which could be prescribed for at-home used in recently diagnosed COVID-19 patients, has been an exciting prospect for infectious disease investigators. In an interview with Contagion® during IDWeek 2021 this week, remdesivir trial author Joshua A. Hill, MD, Assistant Professor at the Fred Hutchinson Cancer Research Center, University of Washington, emphasized the need for proven COVID-19 drugs that could be administered “quickly, easily, readily at home and in primary care clinics.”

“Orals are on the horizon,” Hill said. “I don’t know when, but soon, I hope.”