But efficacy declined following emergence of SARS-CoV-2 Delta variant

Early treatment with the antiviral pill molnupiravir was associated with a roughly 30% reduction in hospitalization or death in non-hospitalized Covid-19 patients at increased risk for progression to severe disease in a planned interim analysis from the phase III, randomized MOVe-OUT trial.

The study was conducted to explore the safety and efficacy of the oral Covid-19 drug in non-hospitalized, unvaccinated patients with mild-to-moderate disease when given within five days of symptom onset.

The peer-reviewed interim trial findings were published online December 16 in the New England Journal of Medicine.

Previously, molnupiravirwas widely considered to be a potential game-changer therapy for the early treatment of at-risk patients with Covid-19, but the MOVe-OUT findings were less robust than anticipated among patients treated following the emergence of the highly transmissible Delta variant.

Patients in the trial treated with molnupiravir prior to Delta’s emergence showed a 50% reduction in hospitalization risk, compared to placebo-treated patients.

Based on the interim MOVe-OUT data, an FDA advisory committee narrowly recommended emergency use authorization (EUA) for molnupiravir in late November by a vote of 13 to 10.

The FDA has not formally acted on the advisory committee’s recommendation, and new concerns about the drug’s safety for use during pregnancy made headlines in the weeks following the committee meeting. Pregnant women were excluded from the MOVe-OUT trial.

The study included patients with newly laboratory confirmed Covid-19 with at least one risk factor for progression to severe disease who were randomized 1:1 to treatment with 800 mg of molnupiravir or placebo twice a day for 5 days.

The primary efficacy endpoint was hospitalization or death within 29 days, and the interim analysis was performed after half of the target enrollment population had been followed for 29 days or more, wrote researcher Carisa De Anda, PharmD, of Merck, Kenilworth, New Jersey, and colleagues.

A total of 1,433 patients underwent randomization, including 716 treated with molnupiravir and 717 treated with placebo. Women were randomly assigned to the active treatment group at a higher rate than men in the interim analysis (difference, 7.6 percentage points). Other characteristics were similar in the two groups.

Among the other main findings:

  • The risk of hospitalization for any cause or death through day 29 was lower in the molnupiravir-treated patients (28 of 385 participants [7.3%]) than in the placebo group (53 of 377 [14.1%]) (difference, −6.8 percentage points; 95% CI, −11.3 to −2.4; P=0.001).
  • In an analysis involving all participants who had undergone randomization, the percentage of patients who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% versus 9.7%; difference, −3.0 percentage points; 95% CI, −5.9 to −0.1).
  • Among certain subgroups, including patients with previous SARS-CoV-2 infection, low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo.

One death was reported in the molnupiravir-treated patients and 9 were reported in the placebo group through day 29, and adverse events were reported in roughly 30% of the molnupiravir-treated patients and 33% of the placebo-treated patients.

“The most frequently reported adverse events (those that occurred in ≥2% of participants in either group) were Covid-19 pneumonia (which occurred in 6.3% of participants in the molnupiravir group as compared with 9.6% of those in the placebo group), diarrhea (2.3% versus 3.0%), and bacterial pneumonia (2.0% versus 1.6%); worsening of Covid-19 was reported as an adverse event in 7.9% as compared with 9.8%,” the study authors wrote. The most frequently reported adverse events (occurring in ≥1% of participants in either group) that were deemed to be related to the trial regimen were diarrhea (1.7% versus 2.1%), nausea (1.4% versus 0.7%), and dizziness (1.0% versus 0.7%).”

Because only unvaccinated patients were included in the trial, it is not clear if the oral antiviral would benefit vaccinated patients with breakthrough infections.

De Anda and colleagues concluded that while vaccination remains the most important medical intervention to reduce Covid-19 hospitalizations and death, “early treatment soon after the onset of symptoms has also been shown to be effective.”

“The monoclonal antibodies bamlanivimab–etesevimab, casirivimab–imdevimab, and sotrovimab are currently authorized treatments for at-risk outpatients with Covid-19,” they wrote.

“Because monoclonal antibodies require administration by means of infusion or injection in a medical setting, oral agents such as molnupiravir that can be administered by the patient at home shortly after diagnosis may be more practical and patient-friendly for non-hospitalized persons; such agents would be important new tools in the Covid-19 treatment armamentarium.”

  1. Early treatment with the antiviral pill molnupiravir was associated with a roughly 30% reduction in hospitalization or death in non-hospitalized Covid-19 patients patients at increased risk for progression to severe disease.

  2. Be aware the the trial’s findings were less robust following the emergence of the Delta variant.

Salynn Boyles, Contributing Writer, BreakingMED™

The MOVe-OUT trial was funded by Merck Sharp and Dohme. Corresponding researcher Carisa De Anda and other MOVe-OUT researchers were employed by Merck. Dr. De Anda reports personal fees and other from Merck Sharp and Dohme Corp, a subsidiary of Merck & Co., Inc. Kenilworth, NJ, outside the submitted work. Other researchers reported receiving personal and other fees from Merck.

Cat ID: 190

Topic ID: 79,190,730,933,190,926,192,927,151,928,925,934