The Medicines and Healthcare products Regulatory Agency (MHRA)’s decision on Thursday makes the UK the first country in the world to approve molnupiravir, just weeks after the UK secured a supply of 480,000 courses of the drug.
Molnupiravir, to be branded Lagevrio in the UK, has been in the global spotlight as a promising Covid-19 treatment since recent interim Phase III trial data showed it reduced the risk of hospitalisation or death by almost 50%.
The pill, which has been touted as a potential game-changer in the fight against the pandemic, works by entering the RNA of the virus and introducing mutations that prevent it from replicating.
MHRA chief executive Dr June Raine said: “Lagevrio is another therapeutic to add to our armoury against Covid-19. It is also the world’s first approved antiviral for this disease that can be taken by mouth rather than administered intravenously.
“This is important, because it means it can be administered outside of a hospital setting, before Covid-19 has progressed to a severe stage.”
Who will receive the treatment?
Clinical trial data indicates that molnupiravir is most effective when administered in the early stages of infection. The MHRA has recommended that individuals begin treatment as soon as possible after a positive Covid-19 test, and within five days of the onset of symptoms.
The regulator has authorised molnupiravir for use in people who have mild to moderate Covid-19 and at least one risk factor for developing severe illness – such as obesity, old age, diabetes or heart disease. The precise characterisation of these risk factors and how they affect patients’ eligibility for the drug will be a defining aspect of molnupiravir’s rollout and its presence in the market.
The drug is to be taken orally, twice a day for five days.
Long-term safety questions
While governments have been largely enthusiastic about molnupiravir’s potential to tackle Covid-19, some experts have expressed concerns about the drug’s safety in humans. One study has suggested that molnupiravir’s mutagenicity – the ability to make genetic changes to a cell – could potentially have harmful long-term effects, such as cancer or birth defects.
Merck said its antiviral was given to lab animals for longer and at higher doses than administered in human studies, and that data showed the drug “is not mutagenic or genotoxic in in vivo mammalian systems”.
Nonetheless, participants in Phase III trials of molnupiravir were instructed to avoid heterosexual sex – or use highly effective contraception – and refrain from donating sperm. MHRA documents on molnupiravir’s regulatory approval also say the drug is not recommended for use in pregnant people, and recommend that those of childbearing potential “use effective contraception for the duration of treatment and for four days after the last dose of Lagevrio”.
In a statement, the MHRA said molnupiravir was approved after “rigorous review of its safety, quality and effectiveness by the UK regulator and the government’s independent expert scientific advisory body”. The regulator has concluded that the drug is “of low risk for genotoxicity or mutagenicity in clinical use”.
Where else will molnupiravir be approved?
Merck has filed for emergency approval for molnupiravir in the US and Canada, and the European Medicines Agency has begun a rolling review of the antiviral. In addition to its supply deal with the UK, the drugmaker has sold 1.7 million treatment courses to the US for approximately $1.2bn.
Other countries, including Australia, South Korea and Singapore, have also made deals to purchase courses of the drug ahead of its pending approval.
With wealthy countries rushing to buy up supplies of molnupiravir, however, there are concerns that poorer nations will once again be left behind.
To boost availability of molnupiravir in lower-income countries, Merck has partnered with several Indian generics makers, and recently entered a voluntary licensing agreement with the Medicines Patent Pool (MPP) to provide affordable international access to the treatment.
Despite the company’s efforts to accelerate global access to molnupiravir, experts have noted that most of Latin America and the Caribbean – not covered by the MPP agreement – have been left without a reliable source of access to the medicine.
Merck plans to manufacture 10 million courses of molnupiravir by the end of the year, and at least 20 million in 2022.