Merck, Ridgeback Likely to be First to Apply for an EUA for an Oral Antiviral to Treat COVID-19

Merck and Ridgeback Biotherapeutics have pulled ahead in the race to get the first Emergency Use Authorization (EUA) for an oral antiviral for COVID-19. They’re expected to file for approval this month.

The companies have announced that the investigational oral antiviral molnupiravir, which they developed together, cut the risk of hospitalization or death by 50 percent in COVID-19 patients with mild or moderate infections.

The results came from an interim report of the company’s phase 3 study. An independent data monitoring committee recommended that Merck stop the study early due to positive results, and the FDA agreed, the companies said. The decision to stop the trial was based on data from 762 patients.

DNA sequencing data on which variant of the SARS-CoV-2 caused COVID-19 was available in 40 percent of the cases in the study. Molnupiravir appeared effective against variants of concern, including Gamma, Delta and Mu, the companies said.

Merck and Ridgeback said they plan to apply for an EUA to the FDA “as soon as possible” based on these findings and plan to submit marketing applications to other regulatory bodies worldwide.

“We will continue to work with regulatory agencies on our applications and do everything we can to bring molnupiravir to patients as quickly as possible,” said Merck CEO Robert Davis.

Some are already getting behind the drug. In June, HHS committed to buy $1.2 billion worth of molnupiravir from Merck if it receives FDA approval.

In the study that was stopped, 7.3 percent of patients (28 people) who received molnupiravir were either hospitalized or died through day 29 following randomization, compared with 14.1 percent of placebo-treated patients (53 people). Through day 29, no deaths were reported in patients who received molnupiravir, compared to eight deaths in patients who received placebo, the companies said.

Study participants were within five days of symptom onset when given the drug or placebo, and had at least one risk factor predisposing them to poor disease outcomes.

But the drug’s safety could become an issue. Originally developed to treat influenza, molnupiravir exerts its antiviral action through introduction of copying errors during viral RNA replication. Some, such as former head of the Biomedical Advanced Research and Development Authority Rick Bright, have expressed concerns that the drug could be mutagenic, meaning it could lead to birth defects. The company Pharmasset had investigated the drug’s active ingredient and abandoned it over similar concerns.

Later, toxicity studies on molnupiravir were carried out and data was provided to regulators in the U.S. and UK, who permitted safety studies in humans to move forward in the spring of 2020.

Merck and Ridgeback said side effect rates in their study were similar between the placebo group and the group that got the study drug. The data aren’t yet peer-reviewed.

An oral drug for COVID-19 could transform treatment of the deadly virus.

Currently, the only approved drug that reduces hospital visits among those with COVID-19 if given early is administered intravenously, so it cannot be taken at home. That’s Gilead  Sciences’ remdesivir.

The FDA has issued an EUA for several monoclonal antibody treatments for COVID-19 for the treatment of mild or moderate cases in adults and kids 12 and over who are at high risk for progressing to severe COVID-19 and/or hospitalization. One monoclonal antibody has an EUA for treatment after exposure to the virus. But these all must be administered in a healthcare setting.

In late September, Pfizer announced that it was beginning a phase 2/3 study on a novel COVID-19 antiviral candidate — a protease inhibitor — administered with a low dose of ritonavir (an antiviral focused on HIV infection) for prevention of illness in adults living in the same household as someone with COVID-19. This is Pfizer’s third study on the candidate (DID, Sept. 28).

Also in late September, Gilead said it’s developing oral treatments for nonhospitalized patients with COVID-19 and hopes to file investigational new drug applications with the FDA by early next year (DID, Sept. 24). — Suz Redfearn