Why is there much excitement about molnupiravir, the investigational new drug for COVID-19?
Pharmaceutical major Merck and Ridgeback Biotherapeutics announced via a press release on October 1 the early results from Phase-3 trials that its anti-viral drug molnupiravir halved the chances of hospitalisation in COVID-19 patients with mild or moderate disease.
Placebo trials involve testing a drug on thousands of people, in which some of them get the drug and some — who are in a placebo group — do not. In the placebo arm, 53 patients of 14% were either hospitalised or had died, whereas in the group that got the drug, 28 — or 7.3% — were hospitalised or succumbed to the infection.
After 29 days of monitoring, no deaths were reported in patients who received molnupiravir, as compared to eight deaths in those who received placebo.
Several noted clinicians have said that these are promising results, and what is particularly encouraging is that molnupiravir is a pill, unlike other drugs — with similar efficacy — used in COVID-19 treatment, which needs to be administered intravenously.
Gilead Sciences, the makers of Remdesivir, too have recently reported better data, compared to last year, on the efficacy of their treatment in mild to moderate COVID-19 patients, but it continues to be an intravenous medicine.
Is molnupiravir a breakthrough for COVID-19 treatment?
While the hospitalisation-avoidance rates are reassuring, there is still much that is unknown about molnupiravir. Complete phase-3 trial data is pending, a publication in a peer-reviewed medical journal is awaited that will explain the process of the trial in the degree of detail that will inspire more confidence among practitioners and drug authorities everywhere.
The company will soon be submitting data to the United States Food and Drugs Administration for a review, after which the drug may be approved for emergency use authorisation. So far, it being a drug that can be administered as pills as part of a five-day regimen is its biggest strength.
The drug has so far been tested only in patients with mild-to-moderate COVID-19, had started treatment within five days of testing positive and had at least one risk factor that increased their risk for severe disease. These include obesity, older age (>60 years), diabetes mellitus and heart disease.
Another positive factor is that recruitment for the phase-3 trial, that originally envisaged recruiting 1,500 patients for testing the drug’s potency, was halted early by an independent data monitoring committee because the data appeared so encouraging that it would be unethical to delay making the drug more widely available.
About 40% of participants had their genomes sequenced to detect the specific variant they were affiliated by and molnupiravir reportedly demonstrated “consistent efficacy” across viral variants Gamma, Delta and Mu.
Adverse events in molnupiravir and placebo groups were 35% and 40%, respectively and incidence of drug-related adverse events were 12% and 11%, respectively. Fewer subjects discontinued study therapy due to an adverse event in the molnupiravir group (1.3%), compared to the placebo group (3.4%).
How does molnupiravir work?
The company name for molnupiravir is ‘EIDD 2801’ the ‘E’ indicating it was developed at Emory University. Antiviral drugs, and this includes the much-in-demand Remdesivir, work by inhibiting the process by which the virus replicates. In the case of molnupiravir, when tested on cultured cells, it works by altering critical enzymes that are necessary for the virus to begin replicating in the body’s host cells.
A key challenge has been that many such antivirals, following a similar mechanism, are not effective as oral pills. However, the Merck pill reportedly appears to have overcome this barrier and adds to its promise as a ‘game-changing’ pill amid the COVID-19 crisis.
Dean Li, Merck’s head of research and development, told medical news website Statnews that the name molnupiravir was also a tangential reference to the weapon of Thor, who is one of the Avengers and a fictional hero of the Marvel Comics Universe. Thor’s hammer is called Mjolnir. “This is a hammer against SARS-CoV-2 regardless of the variant,” said Li. The suffix ‘-avir’ is a common one used for anti-viral drugs
What are the next steps for the drug?
Presumably on the back of encouraging data from Phase-1 and Phase-2 trials, Merck has reportedly begun production of the drug in large numbers. In its statement, it said it expected to produce 10 million courses of treatment by the end of 2021, with more doses expected to be produced in 2022.
Earlier this year, Merck entered into a procurement agreement with the U.S. government, under which Merck will supply approximately 1.7 million courses of molnupiravir to the U.S. government, upon EUA or approval from the U.S. FDA.
The New York Times reports that a course of treatment for the drug could cost $700 (₹50,000 approx.). This is cheaper than the monoclonal antibody therapy, which while being more effective, is a more involved treatment and is not as convenient as popping a pill. Though vaccine availability has improved, hundreds continue to die every day — some despite vaccination — and so an effective drug continues to be very much in demand.
Additionally, Merck has entered into supply and purchase agreements for molnupiravir with other governments worldwide, pending regulatory authorisation, and is currently in discussions with other governments. It is also in talks with generic drug manufacturing companies in 100 low and middle companies to accelerate production.
molnupiravir is also being evaluated for whether it can help prevent transmission of virus, or as prophylaxis, in MOVe-AHEAD, a global, multicentre, randomised, double-blind, placebo-controlled Phase-3 study, which is evaluating the efficacy and safety of molnupiravir in preventing the spread of COVID-19 within households.
