Indian antiviral manufacturers are getting increasingly pivotal as the rollout of the first-ever COVID-19 oral treatment molnupiravir promises to quicken the world’s recovery from the coronavirus pandemic.

Molnupiravir cut the risk of hospitalization or death in fifty percent of people with mild to moderate COVID-19, based on interim phase 3 data. According to Merck & Co, its maker, the efficacy of molnurapiravir was so compelling that clinicians stopped enrollment early in consultation with the FDA. The experimental pill reduced the risk of hospitalization or death across all key subgroups and the efficacy was not affected by the timing of symptom onset or underlying risk factors. On top of it, the yet-to-be-approved drug demonstrated consistent efficacy across SARS-CoV-2 variants Gamma, Delta and Mu.

The pill, which can be taken at home, opens up a broader population to COVID-19 treatments in a true outpatient setting, and the accessibility and affordability of this treatment to all sections of the world becomes a challenge.

Certainly, the orally-consumed molnurapiravir tablets will be far cheaper than the infusion drugs such as remdesivir or mAb cocktails currently used to treat COVID-19. But, the pills could still remain out of reach for much of the global population, experts say. 

And that is where the Indian contract manufacturing organizations (CMOs) come in, as usual, with their unequivocal forte: cost-optimized manufacturing prowess and scalable production capabilities.

Already, Merck, known as MSD in India, has struck voluntary licensing deals with at least eight Indian manufacturers to make low-cost versions of the investigational antiviral. The first-time move allows the firms to manufacture molnupiravir pills not only for the Indian population but also for more than 100 other low- and lower-middle-income countries also.

In another unprecedented move, five of Merck’s partnering firms—Cipla, Sun Pharma, Dr. Reddy’s Lab, Emcure Pharma and Torrent Pharmaceuticals—have reached an agreement to join hands for clinical trials using molnupiravir on Indian patients.

As per the directions of the Subject Expert Committee of India’s regulatory body, one of them (Dr. Reddy’s) will conduct the clinical trial using its version of molnupiravir. The other four companies are required to demonstrate the equivalence of their products to the one used in the clinical trial.

Clearly, the idea is produce as many pills of this desperately needed treatment as possible in the shortest timeframe.

Hetero Drugs, another licensed company, announced interim data from its own late-stage trial of generic molnupiravir in mild COVID-19 patients in early July and submitted an application to regulators for its emergency use.

For APIs, Merck has chosen Divi’s Labs as the authorized manufacturer and is allowed to supply this raw material to its manufacturing partners in India. A leading player in APIs, the Hyderabad-based CMO was in the news recently for successfully developing four key intermediates used in the synthesis of remdesivir, an injectable antiviral.

Many others operating in the API space have also started making molnupiravir, anticipating a huge demand for thepill in the coming days. Hyderabad-based Everest Organics, which announced the commencement of production of molnupiravir API in October, is an example.

Cost estimation studies to arrive at a sustainable generic price for molnupiravir show that the API can be synthesized at a fraction of the current market price through highly cost-efficient processes by Indian CMOs.
“Assuming optimization of molnupiravir synthesis, and a resulting drop in API cost, the U.S. price would be equal to about 161 times the estimated sustainable generic price,” points out a yet-to-be peer-reviewed paper based on Indian API makers jointly written by Melissa Barber, a Harvard University researcher and Dzintars Gotham of Kings College Hospital London.

The U.S. government has ordered 1.7 million treatment courses of molnupiravir, at about $700 per patient.

Merck, which has developed molunapiravir in association with the Miami-based Ridgeback Bio, said it plans to implement a tiered pricing approach based on the World Bank country income criteria to reflect countries’ relative ability to finance their health response to the pandemic.

Reportedly, a large number of players are in a race to launch the pill as they see an urgent need for therapeutics that could keep patients out of hospitals because large swathes of the global population is yet to get immunized against the pandemic virus.

A potent ribonucleoside analog that inhibits the replication of SARS-CoV-2, molnupiravir is also being evaluated for post-exposure prophylaxis. MOVe-AHEAD, a global phase 3 study, is ongoing to assess the efficacy and safety of molnupiravir in preventing the spread of COVID-19 within households.