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Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation  jcm9144@gmail.com 

SPECIAL REPORT #21.24

The United Kingdom approves Molnupiravir for the treatment of COVID-19

The United Kingdom is the first country in the world to approve molnupiravir for the treatment of mild COVID-19. The drug, which has been known for almost forty years, has been developed, in this indication by Ridgeback Biotherapeutics and Merck.

“Molnupiravir has been authorized for use in people who have mild to moderate COVID-19 and at least one risk factor for developing severe illness” U.K. regulator Medicines and Healthcare products Regulatory Agency (MHRA) said on November 4. In the most recent study molnupiravir was shown to reduce the risk of hospitalisation and death by 50%.

Rollout will begin in the U.K. later this month.

Molnupiravir (MK-4482, EIDD-2801) is an orally administered prodrug form of a synthetic nucleoside derivative called EIDD-1931 which inhibits the replication of SARS-COV-2. Molnupiravir inhibits viral replication by promoting mutations in the replication of viral RNA by RNA-directed RNA polymerase. Molnupiravir was invented at Drug Innovation Ventures at Emory (DRIVE) a not-for-profit company wholly owned by Emory University in Atlanta (USA). Molnupiravir was originally tested to find an antiviral drug targeting Venezulean equine encephalitis virus (VEEV).  When the prodrug was further evaluated it showed activity against a series of other RNA viruses including influenza and coronaviruses.  In 2020, a group led by Plemper published in Nature Microbiology the first demonstration that molnupiravir was active against SARS-COV-2 in an animal model. At the time DRIVE had already licensed the drug to Ridgeback Biotherapeutics. In July 2020 Merck, which had been partnering with Ridgeback Biotherapeutics in the past, announced its intention to move molnupiravir into late stage clinical trial and began a one-year phase 2/3 study focusing on hospitalised patients.

In October 2021, Merck reported a preliminary positive outcome of its clinical trial which evaluated molnupiravir 800 mg twice-daily, with similar results of about 50% against various SARS-COV-2 variants and announced that it would be asking the U.S. FDA for an Emergency Use Authorisation (EUA) on October 11.

Several other countries have reported interest in the drug and have placed orders to procure stocks. In October 2021 Merck started a rolling review at the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA).

The development of the drug has been linked with some controversial issues. In November 2019, a few months before the COVID-19 outbreak in Wuhan, Rick Brigth which was directing BARDA since 2016 and moved back to NIH since,  had expressed concerns about the safety of the active metabolite of molnupiravir, claiming it was mutagenic in mice.

On November 6, Pfizer announced that PAXLOVID (PF-07321332 or ritonavir), its  own COVID-19 designed antiviral drug, showed an impressive 89% efficiency in preventing hospitalisation and death. In the overall study population through Day 28, no deaths were reported in patients who received PAXLOVID as compared to 10 deaths in patients who received placebo. The company announced its plan to submit the data as part of its ongoing rolling submission to the U.S. FDA for Emergency Use Authorisation (EUA) as soon as possible 

“Today’s news is a real game-changer in the global efforts to halt the devastation of this pandemic. These data suggest that our oral antiviral candidate, if approved or authorised by regulatory authorities, has the potential to save patients’ lives, reduce the severity of COVID-19 infections and eliminate up to nine out of ten hospitalisations” said Albert Bourla, Chairman and Chief Executive Officer, Pfizer.

Indeed, if these two antiviral drugs prove to be as effective in a real world setting, one can imagine a paradigm shift in the treatment of COVID-19, which we have been advocating since the emergence of the pandemic:

• People at risk should be vaccinated
• Infected subjects should be treated with potent and safe antiviral drugs.

 Paris, November 9, 2021  

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