Merck and Ridgeback Biotherapeutics stated on November 4 that the UK Medicines and Healthcare Products Regulatory Agency had approved Molnupiravir for the treatment of adult patients with mild to moderate COVID-19. This is the first oral drug against COVID-19 in the world!

On October 1 of this year, Molnupiravir presented promising data in Phase III clinical interim analysis, resulting in an early termination and an application to the U.S. Food and Drug Administration (FDA) for an Emergency Use Authorization (EUA). This UK approval is also based on the results of the interim analysis of the Phase III MOVe-OUT clinical trial.

Molnupiravir (MK-4482/EIDD-2801) is a nucleoside analog discovered by DRIVE, a non-profit organization affiliated with Emory University, which inhibits SARS-CoV-2 replication 3-10 times more actively than raltegravir and has shown activity in multiple preclinical SARS-CoV-2 prophylactic, therapeutic, and prophylactic transmission models. Merck and Ridgeback Biotherapeutics co-develop Molnupiravir, with Ridgeback receiving an initial payment from Merck and subsequent mileage payments dependent on clinical development and registration progress.

This trial was supposed to enroll 1,550 participants, but due to an early termination, only 775 have been enrolled so far.

Patients requesting inclusion had to meet all three of the following requirements at the same time.
* COVID-19 symptoms range from mild to moderate.
* At least one risk factor for serious disease (e.g., obesity, age over 60 years, diabetes, and heart disease).
* At the time of randomization, no more than 5 days had passed since the onset of symptoms.

The final patients recruited were composed of 55% Latin Americans, 23% Europeans, and 15% Africans, with about 80% infected with mutant Delta, Gamma, and Mu strains.

The primary indicator in the trial was the percentage of patients who were hospitalized or died of illness within 29 days of randomization to the group, and it was discovered that 7.3% (28/385) and 14.1% (53/377) were seriously ill or died in the Molnupiravir group, respectively. In this trial, eight patient died, but they were all in the control group. That is, Molnupiravir lowered the chances of progressing to severe disease or death by half and reduced the fatality rate to 0%.

The safety of Molnupiravir was also confirmed: for the adverse events, 35% and 40% in the Molnupiravir and control groups were observed, respectively, and for the adverse events related to drug, 12% and 11%, respectively, which were not statistically different. The percentage of discontinuation of treatment due to adverse effects was 1.3% and 3.4%, which was significantly lower in the Molnupiravir group.

What impact will Molnupiravir's approval have on the UK epidemic?

The advantages of Molnupiravir are outstanding. Firstly, its efficacy greatly reduces the chance of mild and moderate COVID-19 patients developing severe disease, which can largely reduce the chance of hospitalization of COVID-19 patients in the UK and effectively alleviate the crowding of medical resources.

Second, the price differential between an oral drug and an intravenous injection is significant, and Molnupiravir, as the first oral COVID-19 drug, may surely save the government a significant amount of medical expenditure. Simultaneously, Molnupiravir is effective against variant strains such as Delta, Gamma, and Mu, which can help limit the threat of SARS-CoV-2 variants.

However, Molnupiravir merely reduces the risk of severe disease and does not prevent infection, according to phase III clinical trials.

In any case, the fact that Molnupiravir was approved in the UK this time demonstrates that its efficacy and safety have been acknowledged. This is unquestionably a boon for the globe, particularly for those patients who may develop severe disease.