The investigational oral antiviral drug molnupiravir is shown to reduce the risk of hospitalization and death in patients with mild or moderate covid-19 by approximately 50%. Pharma companies MERCK (Merck Sharpe Dohme (MSD)) and Ridgeback Biotherapeutics have communicated the results of the interim analysis of phase III of the MOVe-OUT trial and expressed their intention to request the authorization for emergency use (EUA) in the United States as soon as possible and, at the same time, request authorization from other regulatory agencies worldwide. If approved, molnupiravir could be the first antiviral drug to treat Covid-19, say the companies.
The Analysis
Based on data from the interim analysis, 7.3% of patients administered molnupiravir were hospitalized or died within day 29 of randomization (28/385), compared with 14.1% for patients treated with placebo (53/377). In addition, up to the 29th day of dosing, no deaths were reported in patients administered with molnupiravir, compared with eight dying patients treated with placebo. Based on these positive results, the two companies explain, patient recruitment was stopped early, following the recommendation of an independent data monitoring committee and in consultation with the US FDA.
“The pandemic urgently requires new therapeutic options and treatments – said Robert M. Davis, Chief Executive Officer and President of MSD – We are confident that molnupiravir can represent an important treatment option and an essential component of the global effort to combat the pandemic. “
The results of the planned Interim Analysis evaluated the data of 775 patients initially involved in the phase III trial by August 5, 2021. The eligibility criteria required that all patients have a laboratory-confirmed diagnosis of mild or moderate Covid-19, with onset of symptoms within five days of randomization into the study. Molnupiravir reduced the risk of hospitalization and/or death in all major study subgroups; the efficacy was not impacted by the date of onset of symptoms or by the underlying risk factors.
Furthermore, based on the participants enrolled with viral sequencing data (approximately 40%), molnupiravir demonstrated significant efficacy in the viral variants Gamma, Delta and Mu. The incidence of each adverse event was comparable in the molnupiravir and placebo groups (35% and 40%, respectively). At the same time, the incidence of drug-related adverse events was similar (12% and 11%, respectively). Fewer patients discontinued therapy in the molnupiravir control group (1.3%) than in the placebo group (3.4%). “Antiviral therapies that can be taken at home without a patient hospitalization – Wendy Holman, Chief Executive Officer of Ridgeback Biotherapeutics – represent a key therapeutic option today.”
Molnupiravir Production
To ensure access to treatment, even before obtaining the study results, MSD has started production of molnupiravir and intends to produce 10 million doses by the end of 2021and a greater number of doses will be produced in 2022. The company has entered into a procurement agreement with the US government (for approximately 1.7 million doses after the regulatory green light). It is entering into purchase and supply agreements with other governments worldwide, always conditional on the green light to the drug.
Molnupiravir Pricing
Both the companies have expressed their intention to adopt a differentiated pricing policy, capable of reflecting the differing ability of individual states to finance the healthcare response to the pandemic. Another move is voluntary non-exclusive licensing agreements with generic drug manufacturers to accelerate the availability of molnupiravir in more than 100 low- or middle-income countries.
Molnupiravir in India
Merck and Indian generics manufacturers have entered into voluntary license agreements for molnupiravir. A generics manufacturer Hetero Drugs says that it has “accumulated positive data from an open label clinical study of molnupiravir and has submitted these data to the Drug Controller General of India (DCGI).” Some Indian companies that have agreed with MERCK are Cipla Limited, Dr Reddy’s Laboratories Ltd, Emcure Pharmaceuticals Ltd, Sun Pharmaceutical Industries and Torrent Pharmaceuticals Ltd.