Molnupiravir (Lagevrio) is a potent ribonucleoside analog that blocks SARS-CoV-2 replication by acting as a competitive substrate of virally encoded RNA-dependent RNA polymerase.
Molnupiravir (Lagevrio) is the first-ever experimental oral antiviral therapy for the treatment of SARS-CoV-2 (COVID-19) in non-hospitalized adult patients. It is a potent ribonucleoside analog that blocks SARS-CoV-2 replication by acting as a competitive substrate of virally encoded RNA-dependent RNA polymerase. The inhibition leads to rapid mutations of the virus during multiple viral replication cycles, resulting in an antiviral effect.1
Molnupiravir was invented at Drug Innovations at Emory (DRIVE), LLC – a nonprofit biotechnology company wholly owned by Emory University – and is being developed by Merck & Co, Inc, in partnership with Ridgeback Biotherapeutics.2
Current outpatient therapies for COVID-19 include monoclonal antibodies (casirivimab-imdevmiab, bamlanivumab-etesevimab, or sotrovimab), which are subcutaneous or intravenous injections.3 This means that, while considered outpatient therapy, patients still need to go to an outpatient setting for help with administration by a healthcare professional, creating a logistical barrier for patients and health systems.
Merck has filed for Emergency Use Authorization (EUA) with the FDA. The submission is supported by hopeful results from the planned interim analysis of the ongoing MOVe-OUT clinical trial.4
MOVe-OUT is an ongoing phase 3, randomized, placebo-controlled, double-blind, multi-site study that aims to investigate the efficacy and safety of molnupiravir in non-hospitalized adult patients with mild to moderate COVID-19.4 The current primary outcomes of the study are the percentage of participants who are hospitalized and/or die, the percentage with adverse reactions (AEs) and the percentage who discontinue the study intervention because of an AE.
The secondary outcomes of the study were time to sustained resolution or improvement of each targeted sign/symptom at 29 days, time to progression of each sign/symptom, and WHO 11-point outcome score on a scale to categorize clinical progression up to 29 days. Inclusion criteria include adults over 18 years of age, with confirmed documentation of positive COVID-19 test results by polymerase chain reaction (PCR) testing with sample collection <10 days prior to the day of randomization and who had the first signs/symptoms attributable to COVID-19 within 5 days of study randomization.2.4
Exclusion criteria include dialysis patients with estimated glomerular filtration rate <30 ml/min/1.73 m22 and have critical COVID-19 with respiratory failure or are on non-invasive positive pressure ventilation or extracorporeal membrane oxygenation.2.4 Eligible participants will then be randomized to receive a 1:1 ratio of molnupiravir 200 mg or placebo, 3:1 molnupiravir (400 mg or 800 mg) or oral placebo capsules every 12 hours for 5 days, respectively.2.4
In the planned interim analysis of this phase 3 study, 775 patients initially enrolled in the MOVe-OUT study were assigned to 385 in the molnupiravir group and 385 in the placebo group.4 The results show that molnupiravir reduced the risk of hospitalization or death by approximately 50% in all subgroups.
Twenty-eight patients (7.3%) in the molnupiravir group were hospitalized through Day 29, versus 53 patients (14.1%) in the placebo group who either were hospitalized or died; p = 0.0012.4 With an absolute risk reduction of 6.8%, relative risk reduction of 48% and a number of treatments required of 15, this drug provides compelling data to support its use in the treatment of COVID-19.
In an analysis of the 40% participants who had viral sequence data, molnupiravir was shown to be consistently effective against the viral variants of COVID-19, Gamma, Delta and Mu. For key secondary outcome measures, adverse events between molnupiravir (35%) and placebo (40%) were similar and the molnupiravir group (1.3% vs. 3.4%) had fewer participants who discontinued the study due to an adverse event.4
While the Phase 3 MOVe-OUT trial is not expected to be completed until May 2022, the positive results from the interim analysis are promising for molnupiravir. Recently, the European Medicines Agency has also started a rolling review of molnupiravir for the treatment of COVID-19 in adult patients.2
The start could lead to the clinical viability needed for use in the European Union. In November 2021, the United Kingdom was the first to approve molnupiravir.5
Since Merck has committed to allow global access of molnupiravir, they have agreed to enter into a non-exclusive licensing agreement to accelerate the process of its availability in low- and middle-income countries. Merck has also filed an EUA with the FDA for approval of molnupiravir for high-risk adults. This would provide the opportunity for the first oral treatment for COVID-19 at home for patient convenience.2
About the Authors
Kevin Nguyen, PharmD, is a PGY-1 dispensary located at Albert Einstein Medical Center Philadelphia, Pennsylvania.
Nathan Nguyen, PharmD candidate 2023 at Temple University School of Pharmacy.
Mya Yee, PharmD candidate 2023 at Temple University School of Pharmacy.
Katherine Kim, PharmD Candidate 2023 at Temple University School of Pharmacy.
- Fischer W, Eron JJ, Holman W, Cohen MS, Fang L, Szewczyk LJ, Sheahan TP, Baric R, Mollan KR, Wolfe CR, Duke ER, Azizad MM, Borroto-Esoda K, Wohl DA, Loftis AJ, Alabanza P, Lipansky F, Painter WP. Molnupiravir, an oral antiviral treatment for COVID-19. medRxiv [Preprint]. 2021 June 17:2021.06.17.21258639. doi: 10.1101/2021.06.17.21258639. PMID: 34159342; PMCID: PMC8219109.
- Merck and Ridgeback’s oral antiviral drug molnupiravir reduced the risk of hospitalization or death by approximately 50 percent compared to placebo for patients with mild or moderate COVID-19 in positive interim analysis of phase 3 study. Available at Merck.com. Access November 2021.
- Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC, Edwards KM, Gandhi R, Gallagher J, Muller WJ, O’Horo JC, Shoham S, Murad MH, Mustafa RA, Sultan S, Falck-Ytter Y. Guidelines of the Infectious Diseases Society of America for the treatment and management of patients with COVID-19. Infectious Diseases Society of America 2021;
- Efficacy and safety of molnupiravir (MK-4482) in non-hospitalized adult participants with COVID-19 (MK-4482-002). ClinicalTrials.gov Identifier NCT04575597. Updated November 1, 2021. Accessed November 7, 2021. https://clinicaltrials.gov/ct2/show/NCT04575597
- Regulatory body for pharmaceuticals and health care products. (2021, Nov. 4). First oral antiviral for covid-19, Lagevrio (molnupiravir), approved by MHRA. GOV.UK. Retrieved on 8 November 2021 from https://www.gov.uk/government/news/first-oral-antiviral-for-covid-19-lagevrio-molnupiravir-approved-by-mhra.