Indian generic drug manufacturers are poised to make the antiviral pill, molnupiravir, which halved hospitalisations in a trial of high-risk people with COVID-19.

Merck, which developed molnupiravir in collaboration with Ridgeback Biotherapeutics, has awarded non-exclusive, voluntary licensing agreements to eight generic companies in India since April in anticipation of positive trial results.

According to Merck, it has been producing molnupiravir “at risk” and expects to produce 10 million courses of treatment by the end of 2021, the company said a media release last Friday.

Merck cut short the trial of molnupiravir in the light of the good results, and will make an application for emergency use authorisation (EUA) with the US Food and Drug Administration (FDA), “as soon as possible”, the company said.

It will also submit “marketing applications to other regulatory bodies worldwide”, it added.

Australia’s Therapeutic Goods Administration (TGA) granted provisional determination for molnupiravir in August.

Meanwhile, in anticipation of regulatory approval, the Access to COVID-19 Tools (ACT) Accelerator is working to “secure volumes” of the pills for people in LMICs, according to ACT-Accelerator partner Unitaid.

“Effective, simple to use, oral treatments that can avert the progression to severe illness are exactly the kind of breakthroughs we need to get the pandemic under control. Deployed alongside vaccines, such medicines could drive down hospitalizations and deaths due to COVID-19,” said Dr Philippe Duneton, Executive Director of Unitaid shortly after the Merck announcement.

Few treatment options

At present, there are very few treatment options for people infected with COVID-19, and those that exist – such as remdesivir and dexamethasone – are expensive, given intravenously or by injections and only for severely ill people already in hospital. 

White House medical adviser Dr Anthony Fauci told CNN on Sunday that the medicine was “extremely important”.

“It’s a pill that’s given by mouth, so you don’t need anything special other than taking a pill the way you take any pill. And the results are really quite impressive,” said Fauci.

However, he said that it only halved the risk of hospitalisation and to cut this risk by 100% people should “not get infected in the first place”.

Back in April, Merck entered into voluntary licensing agreements with five Indian companies – Cipla, Dr Reddy’s Laboratories, Emcure Pharmaceuticals, Hetero Labs and Sun Pharmaceutical Industries. All are World Health Organization (WHO) pre-qualified manufacturing facilities. 

It has since licensed Aurobindo Pharma, Torrent Pharmaceuticals, and Viatris, to manufacture the drug.

At least four of the companies are already manufacturing generic molnupirvir, which they have been supplying to a trial in India and all eight are ready for global supply, according to MSD India.

When it announced the licensing back in April, Merck said the intention was to enable the manufacturers to “supply molnupiravir to India and more than 100 low and middle-income countries (LMICs)”.

No deaths in trial

The molnupiravir trial involved 775 unvaccinated adults with mild-to-moderate COVID-19 with at least one risk factor for serious illness – most commonly, obesity, being over the age of 60, and living with diabetes and heart disease. 

Only 7,3% of those taking molnupiravir ended up in hospital in comparison to 14,1% of those on the placebo, announced Merck (known as MSD outside the US and Canada) in a media release last Friday.

“Twenty-nine days into the trial, no deaths were reported in patients who received molnupiravir, as compared to eight deaths in patients who received placebo,” it added.

The trial was conducted globally, including at sites in Argentina, Brazil, Canada, Chile, Colombia, Egypt, France, Germany, Guatemala, Israel, Italy, Japan, Mexico, Philippines, Poland, Russia, South Africa, Spain, Sweden, Taiwan, Ukraine, the United Kingdom and the US. 

Meanwhile, in June the US government ordered approximately 1.7 million courses of molnupiravir at a cost of $1.2 billion – about $700/patient – according to a June media release from Merck. 

However, this price is equal to about 35 times the estimated sustainable generic price using current market prices for the active pharmaceutical ingredients (API), according to Melissa J Barber from Harvard University’s Department of Global Health and Population and Dzintars Gotham from King’s College Hospital in London.

“Assuming optimization of molnupiravir synthesis, and a resulting drop in API cost, the US price would be equal to about 161 times the estimated sustainable generic price,” the two researchers noted in a brief published last Friday.

They identified that three companies appeared to be exporting API for molnupiravir –  Optimus Drugs Private, Honour Lab, and Maithri Laboratories. 

Meanwhile, Pfizer and Roche are also racing to develop an antiviral pill for COVID-19, according to Reuters.