Molnupiravir: a key step in the world’s Covid-19 battle?

By Gabriel Ferrante

On October 1st 2021 the pharmaceutical company Merck announced in a press release that their new drug — molnupiravir was able to halve the risk of death or hospitalisations in cases of at risk non-hospitalised patients with mild to moderate Covid-19. The Stage 3 clinical trial was stopped, due to the success of the drug and the potential for this pill to go far in helping others.

Following this Merck has applied for emergency approval from various drug regulatory agencies worldwide in the hope to roll out this new weapon in the antiviral arsenal against the pandemic. On October 20th the UK government announced a deal with Merck to secure 480,000 courses of molnupiravir, with regulatory approval still pending.

The antiviral drug works by cleverly sabotaging the genetic information of coronavirus particles. It is a type of molecule called a nucleoside analogue, meaning it looks very similar to the RNA building blocks of the coronavirus genome, but once it sneaks in it wreaks havoc.

Molnupiravir at first passes for the genomic letter A (Adenine) but once it enters the virus’ RNA genome it shifts configuration, shapeshifting so that it then resembles another letter U (Uracil) causing mutations to build up in the genomes of the virus particles where it was inserted.

This happens until the virus cannot replicate anymore due to the molecular sabotage of its proteins by the sheer number of mutations in its genetic code.

An essential feature of molnupiravir is that it is the only major treatment for early stage Covid-19 which is a pill

For this to be effective the drug needs to be taken very soon after a person develops symptoms. Once a coronavirus patient develops worse symptoms of the disease the immune system, not the virus, is more responsible for causing the damage to your body by overreacting and unleashing a storm of inflammation.

An essential feature of molnupiravir is that it is the only major treatment for early stage Covid-19 which is a pill. Pills are very useful; they can be easily transported, taken at home and don’t need specialists to help you take them. The two other main drugs for early stage Covid-19 are remdesivir by Gilead, and Regeneron’s monoclonal antibody cocktail. Both of which are expensive and can only be used in a hospital because they need to be injected or given through an IV.

The ability to take molnupiravir at home could mean that major pressure on hospitals can be lifted by reducing the load of patients delivered by waves of coronavirus transmission. This is particularly relevant in lower-income countries which haven’t had the same access to vaccines compared to richer nations.

The potential impact of molnupiravir on the continuing pandemic in lower income countries can reduce the impact of the catastrophic unbalance in vaccine coverage caused by the vaccine-greed and lack of solidarity with lower income nations by wealthier nations.

The pricing for the drug would be tiered according to each country’s world bank status

On the other hand, the need for molnupiravir to be used correctly for coronavirus cases and to prevent overuse causes an issue in many nations, where rapid diagnosis of Covid-19 is still quite difficult.

Regarding the potential distribution of the drug Merck announced in a press statement that it has entered procurement agreements with the US Government and has entered supply and purchasing agreements with other governments worldwide for distribution after US FDA or EUA approval.

Additionally, Merck has entered into non-exclusive voluntary licensing agreements with eight general drug manufacturers in India to allow cheap and widespread distribution of the drug in middle- and low-income countries.

The pricing for the drug would be tiered according to each country’s world bank status, which could cause issues with distribution within nations meaning that poorer individuals have less access. However, this lack of access could be compensated for by the higher vaccination rates within richer nations.

It remains to be seen if molnupiravir is approved for emergency use against Covid-19

A week after the press announcement by Merck, controversy occurred. Aurobindo Pharma Ltd and MSN Laboratories, two general drug manufacturers based in India halted their independent clinical trials for molnupiravir. This occurred due to the pill not showing “significant efficacy” against moderate Covid-19 according to a source with the Drug Controller General of India speaking to Reuters.

This seems to have resulted from differences in clinical trial design and standards of measurement. For example, Merck conducted its trials with non-hospitalised patients after ending a clinical trial with hospitalised patients earlier on in the year as antivirals don’t work for late-stage coronavirus.

However, the design of Aurobindo and MSN clinical trials showed ambiguity as to whether they did or didn’t include people in hospital. Additionally, the Merck trial operated under the FDA’s definition for mild to moderate Covid-19 which was measured by blood oxygen levels as being no lower than 93%, and yet the trials by MSN and Aurobindo defined this as blood oxygen levels of 90-93%.

This discrepancy means that selecting patients who are sicker and may be at a later stage of Covid-19 will reduce the efficacy of molnupiravir in preventing severe disease. Continuing and finished trials in India by 6 other companies will be able to provide further results to clarify this issue.

It remains to be seen if molnupiravir is approved for emergency use against Covid-19, but this isn’t the be all and end all. Now pharmaceutical companies have an incentive to develop more coronavirus relevant antiviral therapeutics many companies are stepping up their game. Gilead is developing a pill version of remdesivir, Pfizer, Atea and Roche are also working towards the development of more antiviral drugs. Eventually, the world’s anti-coronavirus medicinal cupboard will be full.

Image: Volodymyr Hryshchenko on Unsplash

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