Merck & Co. (NYSE: MRK) – known as MSD outside the United States and Canada – and Ridgeback Biotherapeutics today announced that molnupiravir (MK-4482, EIDD-2801), an oral antiviral in clinical trials, significantly reduced the risk of hospitalization or death based on the results of the interim analysis of the Phase III of the MOVe-OUT trial conducted on non-hospitalized adult patients at risk with mild or moderate COVID-19.
Based on the data from the interim analysis, molnupiravir reduced the risk of hospitalization or death by about 50%; 7.3% of patients who received molnupiravir were hospitalized or died within day 29 of randomization (28/385), compared with 14.1% for patients treated with placebo (53/377 ); p = 0.0012. Up to the 29th day of dosing, no deaths were reported in patients receiving molnupiravir, compared with 8 dying patients treated with placebo.
Based on the recommendation of an independent data monitoring committee and in consultation with the Food and Drug Administration (FDA), patient recruitment into the study was discontinued early based on these positive results.
Based on these data, MSD intends to apply for an Emergency Use Authorization (EUA) from the US FDA as soon as possible; at the same time, it intends to apply for a marketing authorization to other regulatory agencies worldwide.
“The COVID-19 pandemic urgently requires new therapeutic options and treatments – said Robert M. Davis, Chief Executive Officer and President of MSD – COVID-19 is now a leading cause of death and continues to have a significant impact on patients, their families, society at large as well as healthcare systems around the world. Based on these highly promising results, we are confident that molnupiravir could represent an important therapeutic option and an essential component of the global effort to combat the pandemic. At the same time – Robert M. Davis continues – molnupiravir will represent a new, important piece of the MSD tradition of providing patients with innovative therapeutic options in infectious diseases, precisely where the need is greatest. Consistent with MSD’s tireless commitment to saving and improving the quality of life of patients, we will continue to work with regulatory agencies around the world to ensure that molnupiravir can be available to patients as quickly as possible. “
“From all of us at MSD – concluded Robert M. Davis – I would like to express my heartfelt thanks to all MSD researchers and patients for their essential contribution to the development of molnupiravir”.
“With a virus that continues to circulate widely – ha dichiarato Wendy Holman, Chief Executive Officer di Ridgeback Biotherapeutics – the therapeutic options currently available are exclusively of the infusion type and require access to hospital facilities. This means that antiviral therapies that can be taken at home without hospitalization of the patient represent today a fundamental therapeutic option. The results of the interim analysis are strongly encouraging and we are confident that molnupiravir, if authorized for use, will have a major impact in keeping the pandemic under control. Our partnership with MSD is critical to ensuring timely global access should this drug be approved. We are really proud of this joint effort which has made it possible to achieve these important results in the drug development phase ”.
The results of the Interim Analysis
The results of the planned Interim Analysis evaluated data from 775 patients initially enrolled in the Phase III MOVe-OUT trial before or as of August 5, 2021.
By the time the decision was made to stop enrolling new patients based on the convincing efficacy results of the Interim Analysis, the trial had almost completed the enrollment of the expected 1,550 patients (almost 90% of the total patients being enrolled).
Eligibility criteria required all patients to have a laboratory-confirmed diagnosis of mild or moderate COVID-19, with symptoms appearing within 5 days of randomization into the study.
All patients had to have at least one of the risk factors associated with a low disease outcome upon enrollment in 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. Additionally, based on the participants enrolled with viral sequencing data (approximately 40% of patients enrolled), molnupiravir demonstrated important efficacy in the Gamma, Delta and Mu viral variants.
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 comparable (12% and 11%, respectively).
Fewer patients discontinued therapy in the molnupiravir control group (1.3%) than in the placebo group (3.4%).
MSD’s commitment to grant amolnupiravir, for emergency use or drug approval
Before obtaining the results of the MOVe-OUT study, MSD initiated the production of molnupiravir assuming the entire risk. MSD intends to produce 10 million doses by the end of 2021 and more doses will be produced in 2022.
In the months leading up to today’s announcement, MSD entered into a procurement agreement with the US government; Under this agreement, MSD will provide approximately 1.7 million doses of molnupiravir to the US government once an agreement is reached for emergency use or approval of the drug.
In addition to the agreement with the US government, MSD is entering into procurement and supply agreements with other governments worldwide, always conditional on regulatory clearance, and discussions are underway with many other governments.
About molnupiravir
Molnupiravir (MK-4482 / EIDD-2801) is an oral clinical development drug of a potent ribonucleoside analog that inhibits the replication of SARS-CoV-2, the causative agent of COVID-19.
Molnupiravir has been shown to be active in several preclinical models of SARS-CoV-2, including prophylaxis, treatment and prevention of transmission.
Furthermore, preclinical and clinical data have shown that molnupiravir is active against most of the more common variants of SARS-CoV-2.
Molnupiravir was discovered by Drug Innovations in Emory (DRIVE), LLC, a wholly owned non-for-profit biotech company of Emory University, and is developed by MSD in partnership with Ridgeback Biotherapeutics.
Ridgeback has received an upfront payment from MSD and subsequent payments will be made upon achievement of subsequent development stages and regulatory approvals.
Any profits from the collaboration will be divided equally.
Although the license is held by Ridgeback, all funds for the development of molnupiravir were provided by MSD and Ridgeback’s Wayne and Wendy Holman.
Molnupiravir is also currently being evaluated for post-exposure prophylaxis in the MOVe-AHEAD trial, a global, phase III, multicentre, randomized, double-blind, placebo-controlled study. The MOVe-AHEAD study is evaluating the safety and efficacy of molnupiravir in preventing the spread of COVID-19.