Molnupiravir vs Covid-19: Will the drug live up to the hype?

A global trial, led by the pharmaceutical company Merck — known as MSD outside the United States and Canada — and Ridgeback Therapeutics, has found that the companies’ experimental antiviral drug molnupiravir reduces the risk of hospital admission or death from Covid-19 by approximately 50 percent.

Although this was a small-scale trial, these positive results have led to countries rushing to sign up for supplies of the drug.

In the randomized, phase 3 trial, scientists gave molnupiravir or a placebo to 775 people. All the participants had tested positive for SARS-CoV-2 infections and experienced mild to moderate Covid-19 symptoms that had begun no more than five days earlier.

Every participant had at least one risk factor for severe Covid-19 but had not been admitted to a hospital. Risk factors included obesity, an age of over 60 years, diabetes, and heart disease.

The scientists allocated each of the 775 participants randomly to one of two groups. One group received molnupiravir and the other a placebo. The participants took the capsules twice a day for five days.

Of the 385 patients taking molnupiravir, 28 were admitted to a hospital, compared with 53 of those in the placebo group. Eight of the placebo group participants died, while all those receiving the antiviral were alive at the end of the 29-day study period.

Recruitment into the study has now been halted because of these overwhelmingly positive results. The manufacturer, Merck, is applying for emergency use authorisation from the Food and Drug Administration (FDA).

The Singapore health ministry has signed a purchase agreement for molnupiravir, and the European Medicines Agency is considering a rolling review of the drug.

Merck plans to produce 10 million courses of the treatment in 2021 and more in 2022.

The study results have been greeted with optimism. Prof. Tim Spector, a professor of genetic epidemiology at King’s College London, told MNT: “This is an exciting result from a randomised study of 775 patients, showing major effects in reducing severity and death from a simple pill given at the onset of infection.”

What is molnupiravir?

Molnupiravir belongs to a class of antivirals called mutagenic ribonucleosides. These change the viral genetic material and introduce errors to prevent replication and transcription of the viral genome.

Inside the host cell, molnupiravir is converted to molnupiravir triphosphate. When the virus tries to replicate, molnupiravir triphosphate is incorporated into the viral RNA instead of the nucleoside cytidine, causing a mutation.

The mutation stops the virus from replicating. This keeps numbers of the virus in the body low and should reduce the severity of the disease.

Other drugs that interfere with viral RNA have shown potential as Covid-19 treatments. Remdesivir, an intravenously administered drug that interferes with an enzyme essential for replicating viral RNA, showed early promise.

Although the FDA has granted approval to remdesivir, the World Health Organisation (WHO) no longer recommends it as a Covid-19 treatment, due to insufficient evidence to support its use.

The advantage of molnupiravir is that, unlike all the other potential treatments so far, it is an oral tablet that a person can take outside a clinical setting. At a projected cost of around $700 per person for a 5-day course, it is also more affordable than other drugs. However, this cost is still likely to limit its use.

‘Not a magic pill’

Prof. Sir Peter Horby, a professor of emerging infectious diseases and global health at the University of Oxford, is largely optimistic: “A safe, affordable, and effective antiviral would be a huge advance in the fight against Covid.”

However, he retained a note of caution: “It is important to remember that the absolute risks were 14 percent reduced to 7 percent, so quite a lot of people need to be treated to prevent one hospitalization or death. This means the drug needs to be very safe and affordable.”

This caution was echoed by Prof. William Schaffner, a professor of infectious diseases at the Vanderbilt University School of Medicine, who said: “In the studies in very high risk patients, it reduced the level of serious disease by only half. It’s not a magic pill.”

He added: “In research settings, you can ensure that people take the pill as directed. In practice, there is usually a lower success rate than in clinical trials.”

Dr Peter English, a retired consultant in communicable disease and a past chair of the

British Medical Association Public Health Medicine Committee, has also expressed doubts:

“The problem for antivirals like Merck’s molnupiravir is that they would have to be used before people are (usually) deemed ill enough to need anything other than symptomatic self-care treatment.”

“Unless an antiviral medication could be made so cheap and so safe that it can be used ‘on spec’ by people who might have Covid-19, [it is] unlikely to be widely useful,” he adds.

Safety concerns

Despite widespread optimism following the study results, some experts have raised concerns about the safety of a drug that works by causing mutations.

As molnupiravir causes viral RNA to mutate, there are concerns that it might cause mutations in host cells, as well. One study in animal cell cultures found mutations in cells treated with molnupiravir.

This has led to worries that the drug might cause cancers or birth abnormalities. The authors of the animal cell study recommend that this mutagenic potential be assessed in vivo, focusing on rapidly dividing cells. Additionally, they recommend monitoring to assess potential genotoxic side effects.

Cautious optimism

In this trial, molnupiravir was effective against all variants, including the Delta variant, which was shown in a recent study to have a 235 percent increased risk of intensive care unit admission, compared with the original variant.

These positive results applied to people who had received molnupiravir soon after the onset of mild

to moderate symptoms. A previous trial showed no benefit in giving the drug to patients already in hospital with Covid-19.

As an early treatment, molnupiravir could, Prof. Schaffner agrees, “offer another opportunity to prevent serious disease.”

So, is molnupiravir the drug we have been waiting for to bring Covid-19 under control? Perhaps, but the evidence is not yet conclusive.

Prof. Spector is among those keen to see more trial results. “We are told there were few side effects, but it would be good to know more details and see a full peer-reviewed publication,” he said. “But if this pans out, it will be a major game-changer for [Covid-19] treatment and possibly other viruses.”- Extracted from Medical News Today

You Might Also Like

Comments

Take our Survey

We value your opinion! Take a moment to complete our survey