Merck, Ridgeback File First EUA Application for an Oral Antiviral to Treat COVID-19

Merck and Ridgeback Biotherapeutics have become the first companies to file an application seeking Emergency Use Authorization (EUA) for an oral antiviral that treats COVID-19 — which could transform treatment of infections with the deadly virus.

The companies announced their filing yesterday and said a phase 3 trial showed the investigational antiviral molnupiravir, which they co-developed, cut the risk of hospitalization or death by 50 percent in COVID-19 patients with mild or moderate infections (DID, Oct. 4).

“The extraordinary impact of this pandemic demands that we move with unprecedented urgency, and that is what our teams have done by submitting this application for molnupiravir to the FDA within 10 days of receiving the data,” said Merck CEO Robert Davis.

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.

Molnupiravir appeared effective against variants of concern, including Gamma, Delta and Mu, the companies said. 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.

Some are already getting behind the oral drug.

In June, Merck entered into a procurement agreement with the U.S. government to supply about 1.7 million courses of molnupiravir at a price of $700 per course upon EUA or approval from the FDA.

Also, Merck entered into nonexclusive voluntary licensing agreements for molnupiravir with Indian generic manufacturers to make the drug in about 100 low- and middle-income countries following approvals or emergency authorization by local regulatory agencies.

Additionally, the company said it has struck supply and advance purchase agreements for molnupiravir with other governments, pending regulatory authorization, and is currently in discussions with additional governments.

Merck said it plans to implement a tiered pricing approach based on World Bank country income criteria to reflect countries’ relative ability to finance their health response to the pandemic.

In anticipation of a potential authorization, Merck said it has been producing molnupiravir at risk and expects to produce 10 million courses of treatment by the end of 2021 and expects to increase that number in 2022.

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 were 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.

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 authorized emergency use of several monoclonal antibody treatments for COVID-19 for the treatment of mild or moderate cases in adults and kids age 12 and over who are at high risk for progressing to severe COVID-19 and/or hospitalization. And 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 oral 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 is developing oral treatments for nonhospitalized COVID-19 patients and hopes to file investigational new drug applications with the FDA by early next year (DID, Sept. 24). — Suz Redfearn