Molnupiravir (Lagevrio, MK-4482) COVID-19 Oral Antiviral Description
Molnupiravir (Lagevrio) (Molxvir) (emorivir) is an oral antiviral developed initially to treat influenza. Molnupiravir is an orally bioavailable form of a potent ribonucleoside analog that inhibits replicating multiple RNA viruses, including SARS-CoV-2, the causative agent of COVID-19.
Initially developed at Emory University, Miami, Florida-based Ridgeback Biotherapeutics L.P., and its partner Merck conducted a comprehensive nonclinical program to characterize the safety profile of molnupiravir, including assays such as Big Blue and PIG-a, which are designed to provide a robust measure of a drug or chemical's ability to induce mutations in vivo. In addition, animals were administered molnupiravir for more extended and higher doses (mg/Kg) than those employed in human studies. These studies indicate that molnupiravir is not mutagenic or genotoxic in vivo mammalian systems.
Merck's Molnupiravir (MK-4482) consists of the nucleoside analog N4-hydroxycytidine. Molnupiravir has been evaluated against coronaviruses, including SARS-1, MERS-CoV. In addition, Molnupiravir is active in several models of SARS-CoV-2, including for prophylaxis, treatment, and prevention of transmission. Molnupiravir is a mutagenic nucleotide analogue, the underlying biochemical mechanisms with the purified RdRp complex of SARS-CoV-2.
The U.S. NIH highlighted a non-peer-reviewed phase 2 study on June 17, 2021, that concluded by saying, 'Molnupiravir is the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.'
And on October 23, 2021, the NIH PubMed reported the phase 2/3 NCT04575597 study recently released that molnupiravir significantly reduced the risk of hospitalization or death in adults experiencing mild or moderate COVID-19. To benefit individual and public health, clinical applications of molnupiravir to promptly treat COVID-19 patients and prevent SARS-CoV-2 virus transmission may be expected.
On November 4, 2021, the U.K. Medicines and Healthcare products Regulatory Agency granted authorization in the United Kingdom for molnupiravir, known locally as Lagevrio. In addition, the U.K. published a Summary of Product Characteristics for Lagevrio 200 mg hard capsules on November 4, 2021. Form: Swedish Orange, opaque, size 0 (approximately 21.7 mm x 7.6 mm) hard capsule, printed with MSD corporate logo on the cap and "82" on the body in white ink.
The U.S. FDA's Antimicrobial Drugs Advisory Committee met on November 30, 2021, and voted to 13 to 10 to endorse Molnupiravir. Merck's presentation and the meeting agenda were posted on November 26, 2021. And on December 16, 2021, Data from the MOVe-AHEAD phase 3 study demonstrated that early treatment with molnupiravir significantly reduced the risk of hospitalization or death in high-risk, unvaccinated adults with COVID-19.
On December 23, 2021, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) to Merck Sharp & Dohme Corp. for molnupiravir for the treatment of mild-to-moderate COVID-19 in adults with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate. It is not authorized for the pre-exposure or post-exposure prevention of COVID-19. Under the EUA, fact sheets that provide essential information about using molnupiravir to treat COVID-19 as authorized must be made available to healthcare providers, patients, and caregivers. An updated FAQ was also published by the FDA.
On January 12, 2022, the U.S. Clinician Outreach and Communication Activity conducted a digital call - 'What Clinicians Need to Know About the New Oral Antiviral Medications for COVID-19.'
Molnupiravir [USAN] RN: 2349386-89-4. Lagevrio (PLGB 53095/0089); UNII: YA84KI1VEW, InChIKey: HTNPEHXGEKVIHG-QCNRFFRDSA-N; PubChem CID145996610; CAS Number 2349386-89-4; DrugBank DB15661; Chemical Formula: C13H19N3O7; Molecular Formula: C13H19N3O7; CHEBI: 180653
Molnupiravir (Lagevrio, MK-4482) COVID-19 Oral Antiviral Use With SARS-CoV-2 Virus Variants (Omicron)
Preclinical and clinical data have shown molnupiravir to be active against the most common SARS-CoV-2 variants. The oral drug is yet to be evaluated against Omicron in clinical studies. As of January 20, 2022, the U.S. NIH's OpenData Portal reported in vitro Therapeutic Activity against the Omicron variant. But, given the breaking nature of these releases, Omicron data should be interpreted with caution. And the CViSB Team at Scripps Research is tracking the prevalence of SARS-CoV-2 (hCoV-19) variants with lineage and mutation reports.
On January 19, 2022, the NIH updated the COVID-19 Treatment Guidelines Panel addresses the fact that the B.1.1.529 (Omicron) variant is now the dominant SARS-CoV-2 variant in all U.S. Department of Health and Human Services' ten regions. The purpose of this statement is to provide clinicians with guidance on the use of Molnupiravir for the treatment of nonhospitalized patients with COVID-19 who are at high risk of progressing to severe disease.
Molnupiravir (Lagevrio, MK-4482) COVID-19 Oral Antiviral Availability
Merck entered into a procurement agreement with the U.S. Government in November 2021 for three million doses. The U.S. Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response (ASPR) oversees the allocations of Paxlovid to state and territorial health departments, and select Health Resources & Services Administration funded health clinics and pharmacies. AmerisourceBergen is the sole distributor of molnupiravir in the U.S.
Since December 13, 2021, the ASPR released about 700,000 Molnupiravir doses to U.S. states, territories, and agencies, including 399,920 released on January 11, 2022.
As of January 20, 2022, Merck has shipped molnupiravir to 30 countries where Molnupiravir is authorized: Denmark, Europe, India, Sri Lanka, and Taiwan, and has limited availability in the USA, Canada, India; Thailand, Australia, Philippines, Singapore, South Korea, Vietnam, Japan. And Merck announced on January 18, 2022, it will allocate up to 3 million courses of molnupiravir to UNICEF throughout the first half of 2022 for distribution in more than 100 low- and middle-income countries following regulatory authorizations.
Merck previously announced in October 2021, that the company has entered into non-exclusive voluntary licensing agreements for molnupiravir with established generic manufacturers to accelerate the availability of molnupiravir in more than 100 low- and middle-income countries following approvals or emergency authorization by local regulatory agencies.
Molnupiravir COVID-19 Oral Antiviral Brands
Molnupiravir is the original generic brand; in Europe and the U.K. (Lagevrio); in India (Molxvir) (Molnulup, Molulife, Molena).
Molnupiravir (Lagevrio, MK-4482) COVID-19 Oral Antiviral History
On October 1, 2021, Merck and Ridgeback Biotherapeutics announced that molnupiravir significantly reduced the risk of hospitalization or death at a planned interim analysis of the Phase 3 MOVe-OUT trial in at-risk, non-hospitalized adult patients with mild-to-moderate COVID-19.
On June 19, 2020, Miami-based Ridgeback Biotherapeutics announced the launch of two Phase 2 clinical trials to test the efficacy of EIDD-2801 as an antiviral treatment for COVID-19. On July 1, 2020, Merck and Ridgeback Biotherapeutics L.P. announced that the U.S. Federal Trade Commission granted early termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act. As a result, all closing requirements have been completed for the previously announced partnership transaction to advance the development of EIDD-2801, an investigational orally-available antiviral agent currently in early clinical development to treat patients with COVID-19.
A study published on April 29, 2020, found the potency of NHC/EIDD-2801 against multiple CoVs, and oral bioavailability highlights its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic CoVs.
On April 15, 2021, the companies announced, 'Based on a planned interim analysis of data from the Phase 2, a dose-finding portion (Part 1) of two ongoing placebo-controlled Phase 2/3 trials evaluating molnupiravir administered twice a day for five days in outpatients (MOVe-OUT) and hospitalized patients (MOVe-IN) with COVID-19, and from a previously completed Phase 2a dose-ranging study in outpatients, the decision has been made to proceed with the Phase 3 portion (Part 2) of MOVe-OUT in outpatients with COVID-19, evaluating the 800 mg dose of molnupiravir twice daily. Data from MOVe-IN indicate that molnupiravir is unlikely to demonstrate a clinical benefit in hospitalized patients, who generally had a longer duration of symptoms before study entry; therefore, the decision has been made not to proceed to Phase 3.'
It was developed at Emory University in Georgia by its drug innovation company, Drug Innovation Ventures at Emory. When the COVID-19 pandemic began, DRIVE quickly repurposed a broad-spectrum antiviral drug it had been developing for infectious diseases. Emory University President Gregory L. Fenves discussed Emory's role in this discovery and the university's long history of research excellence on October 18, 2021. The oral antiviral was later acquired by Ridgeback Biotherapeutics, which partnered with Merck & Co. to continue developing the antiviral.
New Jersey-based Merck (NYSE: MRK), known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world's most challenging diseases in pursuit of their mission to save and improve lives.
Florida-based Ridgeback Biopharmaceuticals was co-founded by CEO Wendy Holman and Dr. Wayne Holman, a scientific advisor, focusing on developing antiviral medications for epidemic and pandemic risk diseases.
Molnupiravir (Lagevrio, MK-4482) COVID-19 Oral Antiviral Indication
Molnupiravir oral antiviral is indicated to mitigate SARS-CoV-2 betacoronavirus infection and block transmission, for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate.
Molnupiravir is not authorized for use in patients younger than 18 years of age because molnupiravir may affect bone and cartilage growth. It is not authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in patients hospitalized due to COVID-19 because the benefit of treatment has not been observed in people when treatment started after hospitalization due to COVID-19. Furthermore, before initiating treatment with molnupiravir, it should be assessed whether an individual of childbearing potential is pregnant or not, if clinically indicated.
Molnupiravir is available by prescription only and should be initiated as soon as possible after a diagnosis of COVID-19 and within five days of symptom onset. No drug interactions have been identified based on the limited available data on the emergency use of molnupiravir. And no clinical drug-drug interaction trials of molnupiravir with concomitant medications, including other treatments for mild to moderate COVID-19, have been conducted.
Molnupiravir (Lagevrio, MK-4482) COVID-19 Oral Antiviral Use While Pregnant, Breastfeeding or Reproductive Age
In the U.S., UK, and India, Lagevrio is not recommended during pregnancy. Women of childbearing potential should use effective contraception for the duration of treatment and four days after the last dose of Lagevrio (molnupiravir). And in the U.S. and Molnupiravir is not recommended for use in patients who are pregnant. Based on findings from animal reproduction studies, molnupiravir may cause fetal harm when administered to pregnant individuals. There are no available human data on the use of molnupiravir in pregnant individuals to evaluate the risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
There is a pregnancy surveillance program that monitors pregnancy outcomes in individuals exposed to molnupiravir during pregnancy. Moreover, patients exposed to molnupiravir during pregnancy should report the exposure by contacting Merck by phone at 1-877-888-4231, or online at pregnancyreporting.msd.com.
Nonclinical studies to fully assess the potential for molnupiravir to affect offspring of treated males have not been completed. The risk beyond three months after the last dose of molnupiravir is unknown.
And there are no data on the presence of molnupiravir or its metabolites in human milk. It is unknown whether molnupiravir has an effect on the breastfed infant or effects on milk production. Based on the potential for adverse reactions in the infant from molnupiravir, breastfeeding is not recommended during treatment with molnupiravir and for 4 days after the final dose.
Molnupiravir (Lagevrio, MK-4482) COVID-19 Oral Antiviral Dosage
The recommended dose of Lagevrio is 800 mg (four 200 mg capsules) taken orally every 12 hours for five days. The safety and efficacy of molnupiravir when administered for periods longer than five days have not been established. Therefore, Lagevrio should be administered as soon as possible after a diagnosis of COVID-19 has been made and within five days of symptom onset. If the patient misses a dose of Lagevrio within 10 hours of the time it is usually taken, the patient should take it as soon as possible and resume the normal dosing schedule. If a patient misses a dose by more than 10 hours, the patient should not take the missed dose and instead take the next dose at the regularly scheduled time. The patient should not double the dose to make up for a missed dose.
Pediatric population: The safety and efficacy of Lagevrio in patients below 18 years of age have not been established. No data are available.
Molnupiravir (Lagevrio, MK-4482) COVID-19 Oral Antiviral Side Effects
There are limited clinical data available for molnupiravir. Serious and unexpected adverse events may occur that have not been previously reported with molnupiravir use. No contraindications have been identified based on the limited available data on the emergency use of molnupiravir authorized under EUA.
An analysis of a phase 3 trial of subjects with mild to moderate COVID-19 treated with molnupiravir (n=386), the most common adverse reactions (≥1% of subjects) reported during treatment and during 14 days after the last dose were diarrhea (3%), nausea (2%), dizziness (1%) and headache (1%) all of which were Grade 1 (mild) or Grade 2 (moderate). Serious AEs occurred in 7% of subjects receiving molnupiravir and 10% receiving placebo; most serious AEs were COVID-19 related.
In July 2021, a study discussed decoding molnupiravir-induced mutagenesis in SARS-CoV-2 - Available evidence suggests that molnupiravir could become a paradigmatic example in the use of lethal mutagenesis as an antiviral strategy. However, there are inherent risks in this approach. NHC can be metabolized by the host cell to the 2′-deoxyribonucleoside form by the ribonucleotide reductase and then incorporated into the host cell DNA. The mutagenic effect of NHC has been shown in animal cell cultures, raising concerns on the potential risk of molnupiravir-induced tumorigenesis and the emergence of detrimental mutations in sperm precursor cell generation and embryo development.
The University of North Carolina researchers recently published a study in The Journal of Infectious Diseases on August 1, 2021, exposing hamster cells to the drug for 32 days. Molnupiravir was found about 100-fold more active than ribavirin or favipiravir against severe SARS-CoV-2, with antiviral activity correlated to the level of mutagenesis in virion RNA. However, NHC also displays host mutational activity in an animal cell culture assay, consistent with RNA and DNA precursors sharing a common intermediate of a ribonucleoside diphosphate. These results indicate highly active mutagenic ribonucleosides may hold risk for the host.
On January 5, 2022, Indian Council for Medical Research (ICMR) Chief Dr. Balram Bhargava said 'the antiviral drug Molnupiravir has major safety concerns. It can cause teratogenicity, mutagenicity, and cartilage damage, and can also be damaging to muscles. Contraception will have to be done for three months if this drug is given because the child born could have problems due to teratogenic influence," he told media in India.
VAERS is a passive reporting system, meaning it relies on individuals to send in reports of their experiences. However, anyone can submit information to VAERS, including parents and patients. And submit adverse event and medication error reports, using FDA Form 3500, to FDA MedWatch.
Molnupiravir (Lagevrio, MK-4482) COVID-19 Oral Antiviral Pricing
Merck confirmed plans to implement a tiered pricing approach on November 10, 2021, based on World Bank country income criteria to reflect countries' relative ability to finance their health response to the pandemic. The Bill & Melinda Gates Foundation announced plans to create generic versions of Molnupiravir for low-income countries on October 19, 2021. The WHO 'welcomed the signing of a voluntary licensing agreement by the Medicines Patent Pool and MSD to facilitate affordable access to molnupiravir' on October 27, 2021.
On January 4, 2022, Dr Reddy's Laboratories announced that it would sell a course of its version of molnupiravir in India for 1400 rupees (US$18·85).
A modeling study published on October 1, 2021, conducted by researchers from Harvard T. H. Chan School of Public Health and King's College Hospital estimated cost-based generic prices for molnupiravir for the treatment of COVID-19 infection. The U.S. government has already ordered 1.7 million treatment courses, at about $700/patient. This price equals about 35 times the estimated sustainable generic price using current market prices for the active ingredient (API) observed in our analysis. Assuming optimization of molnupiravir synthesis and a resulting drop in API cost, the U.S. price would equal about 161 times the estimated sustainable generic price.
Molnupiravir COVID-19 Oral Antiviral Payments in the U.S.
CMS has released a set of toolkits for providers, states, and insurers to help the health care system prepare and assist in swiftly administering COVID-19 products once they become available. CMS identified specific code(s) for each COVID-19 product for Medicare payment.
Molnupiravir (Lagevrio, MK-4482) COVID-19 Oral Antiviral News
January 20, 2022 - The Medicines Patent Pool announced today that it has signed agreements with 27 generic manufacturing companies for the manufacturing of the oral COVID-19 antiviral medication molnupiravir and supply in 105 low- and-middle-income countries.
January 20, 2022 - The Therapeutic Goods Administration in Australia issued a provisional Approval for Lagevrio® (molnupiravir). Australia has secured access to 300,000 treatment courses of Lagevrio.
January 18, 2022 - Merck and Ridgeback Biotherapeutics announced the signing of a long-term supply agreement with the United Nations Children's Fund (UNICEF) to facilitate broad global access for molnupiravir. Under the agreement, Merck will allocate up to 3 million courses of molnupiravir to UNICEF throughout the first half of 2022.
January 13, 2022 - The Lancet published: The role of antiviral treatment in the COVID-19 pandemic.
January 7, 2022 - Lupin Limited announced the launch of Molnupiravir in India under the brand name Molnulup.
January 7, 2022 - Media reported Merck announced a phase 3 study that found Molnupiravir effective. The drug is yet to be evaluated against Omicron in clinical studies, it added.
January 5, 2022 - Yale Medicine published an article: 9 Things You Need To Know About Molnupiravir, a New COVID-19 Pill.
December 29, 2022 - Walmart, Inc. confirmed certain Walmart and Sam's Club pharmacies will dispense the FDA-authorized Molnupiravir as supplies allow.
December 28, 2021 - Molnupiravir will be manufactured by 13 companies for restricted use in India for the treatment of adult patients with COVID-19 and people at high risk of progression of the disease.
December 23, 2021 - The U.S. Food and Drug Administration issued an emergency use authorization for molnupiravir to Merck Sharp & Dohme Corp.
December 22, 2021 - Merck and Ridgeback Biotherapeutics announced that the U.K. Government would purchase an additional 1.75 million patient courses of molnupiravir (LAGEVRIO®). With this additional procurement agreement, which follows a previously announced agreement for 480,000 courses of treatment, the U.K. has now committed to purchasing a total of 2.23 million courses of molnupiravir. Molnupiravir is currently available in the U.K., and patients have started to receive treatment.
December 22, 2021 - France announced canceling its order for Merck & Co's COVID-19 antiviral pill.
December 16, 2021 - Merck and Ridgeback Biotherapeutics announced the NEJM published findings from the Phase 3 MOVe-OUT trial evaluating molnupiravir in non-hospitalized high-risk adults with mild to moderate COVID-19. Data from MOVe-OUT demonstrated that early treatment with molnupiravir significantly reduced the risk of hospitalization or death in high-risk, unvaccinated adults with COVID-19.
December 16, 2021 - Reuters reported Denmark approved the molnupiravir antiviral pill for COVID-19 patients at risk of serious illness, including the elderly.
December 13, 2021 - The journal Nature published a news article: Merck's COVID pill loses its luster: what that means for the pandemic.
December 8, 2021 - Researchers from the University of Oxford started recruiting participants for a first-of-its-kind clinical trial to test novel antiviral COVID-19 treatments for use early on in the illness by people in the community with COVID-19 and those who are at higher risk of complications.
December 4, 2021 - India media reported the drug regulator's subject expert committee is meeting on December 6, 2021, to examine applications of drugmakers seeking marketing authorization for molnupiravir for Covid-19 treatment.
December 3, 2021 - Health Canada announced an agreement with Merck for up to 500,000 courses of its treatment, with an option to add 500,000 more pending approval.
November 30, 2021 - Merck and Ridgeback Biotherapeutics provided the following statement - "The positive outcome of today's FDA Advisory Committee meeting, following a comprehensive review of molnupiravir, including the compelling data from the MOVe-OUT study demonstrating a significant reduction in hospitalizations and deaths, is a critical step toward bringing this promising oral medicine for COVID-19 to appropriate patients in the U.S."
November 30, 2021 - The Drug Evaluation and Research Antimicrobial Drugs Advisory Committee digitally met to review clinical information regarding Merck's Molnupiravir; Introduction, John Farley, MD, MPH Director; Merck Introduction, Sean Curtis, MD, MPH Senior Vice President, Global Regulatory Affairs and Clinical Safety Merck & Co., Inc.; Questions. The FDA committee voted positive, with 13 yes and ten no votes.
November 26, 2021 - The U.S. FDA Center for Drug Evaluation and Research Antimicrobial Drugs Advisory Committee Meeting agenda and for November 30, 2021, was posted, as was Merck's presentation.
November 26, 2021 - Merck and Ridgeback Biotherapeutics provided an update on the MOVe-OUT phase 2/3 clinical study of molnupiravir. Data are now available from all enrolled participants (n=1433); molnupiravir reduced the risk of hospitalization or death from 9.7% in the placebo group (68/699) to 6.8% (48/709) in the molnupiravir group, for an absolute risk reduction of 3.0% (95% confidence interval [CI]: 0.1, 5.9; nominal p-value=0.0218) and a relative risk reduction of 30% (relative risk 0.70; 95% CI: 0.49, 0.99). Nine deaths were reported in the placebo group and one in the molnupiravir group. The adverse event profile for molnupiravir remained consistent with the profile reported at the planned interim analysis. Based on the study design, the definitive evaluation of efficacy was considered complete at the planned interim analysis, when the statistical criterion for success was met, and enrollment in the study was discontinued at the recommendation of the external Data Monitoring Committee and agreed to by the U.S. FDA.
November 23, 2021 - The EMA is evaluating an application for marketing authorization for Lagevrio (molnupiravir) and will assess the benefits and risks of under a reduced timeline and could issue an opinion within weeks if the data submitted are sufficiently robust and complete to show the efficacy, safety, and quality of the COVID-19 oral antiviral.
November 19, 2021 - The EMA announced that adults with COVID-19 who do not require supplemental oxygen and are at increased risk of developing severe COVID-19 could be administered Lagevrio as soon as possible after a diagnosis within five days of the start of symptoms. The medicine, available as capsules, should be taken twice a day for five days. About one month after treatment started, 7.3% of patients (28 out of 385) who took Lagevrio compared with 14.1% (53 out of 377) of patients who took placebo had been hospitalized or had died; none of the patients in the Lagevrio group died compared with eight patients in the placebo group.
November 17, 2021 - Merck and Ridgeback Biotherapeutics announced that new Phase 3 data for molnupiravir will be presented as a late-breaking poster (#LB-5319) at the American Society of Tropical Medicine and Hygiene 2021 Annual Meeting. The data will be available on Nov. 17 at 9 a.m. E.T. and presented during Poster Session C from 11 a.m.-12:30 p.m. E.T. on Saturday, Nov. 20.
The presentation will include data from the molnupiravir clinical development program, emphasizing the interim results from the MOVe-OUT trial, including baseline characteristics of the study population and additional details on efficacy and safety. The companies previously announced positive results from a planned interim analysis of the trial, which evaluated molnupiravir 800 mg twice-daily in non-hospitalized, unvaccinated adult patients with laboratory-confirmed mild-to-moderate COVID-19, symptom onset within five days of study randomization, and at least one risk factor associated with poor disease outcomes (e.g., heart disease, diabetes).
November 11, 2021 - Sun Pharmaceutical Industries Limited announced that Merck and Ridgeback's molnupiravir under the brand name Molxvir® in India.
November 10, 2021 - Merck and Ridgeback Biotherapeutics announced that the Japanese government would purchase, upon authorization or approval, approximately 1.6 million courses of molnupiravir (MK-4482, EIDD-2801).
November 9, 2021 - Merck and Ridgeback Biotherapeutics announced that the U.S. government would exercise two of its options to purchase a total of 1.4 million additional courses of molnupiravir if the U.S. FDA grants the oral antiviral medicine EUA or Approval for approximately $1 billion.
November 8, 2021 - The EMA and the Heads of Medicines Agencies have agreed on the need for additional guidance on COVID-19 treatments across the E.U. The EMA's Executive Director requested the review under Article 5(3) of Regulation 726/2004 following preliminary discussions with EMA's COVID-19 pandemic task force.
November 8, 2021 - Thailand's Public Health Minister Anutin Charnviraku confirmed to local media the approval to buy 50,000 courses, equal to 2 million pills, of molnupiravir.
November 4, 2021 - The U.K. Medicines and Healthcare products Regulatory Agency announced today that the antiviral Lagevrio (molnupiravir) is safe and effective at reducing the risk of hospitalization and death in people with mild to mild-moderate COVID-19 who are at increased risk of developing severe disease. Molnupiravir has been authorized for use in people with mild to moderate COVID-19 and at least one risk factor for developing severe illness.
November 2, 2021 - The Wire in India published: Everything You Need To Know About Molnupiravir, Merck's New High-hope COVID Drug.
November 1, 2021 - The media magazine Forbes published an article: Supercharging New Viral Variants: The Dangers of Molnupiravir (Part 1). Harming Those Who Receive It: The Dangers Of Molnupiravir (Part 2).
October 29, 2021 - Barron's reported - Merck's Covid Antiviral Isn't Just a Quick Win. It Could Lift Revenue for Years.
October 28, 2021 - India-based OPTIMUS group announced the successful completion of the Molnupiravir oral capsule phase 3 clinical trial. On May 25, 2021, Optimus Pharma confirmed having internally developed the active pharmaceutical ingredient and the formulations for the product; it had filed for clinical trials in India.
October 27, 2021 - The Medicines Patent Pool (MPP) and Merck announced a voluntary licensing agreement to facilitate affordable global access for molnupiravir. Merck, Ridgeback Biotherapeutics, and Emory University will not receive royalties for sales of molnupiravir under this agreement for as long as COVID-19 remains classified as a Public Health Emergency of International Concern by the WHO.
October 25, 2021 - Merck and Ridgeback Biotherapeutics announced that the EMA initiated a rolling review for molnupiravir. Merck plans to work with the EMA's Committee for Medicinal Products for Human Use (CHMP) to complete the rolling review process to facilitate initiating the formal review of the Marketing Authorization Application.
October 19, 2021 - The Bill & Melinda Gates Foundation announced a commitment of up to $120 million to accelerate access to the investigational antiviral drug molnupiravir for lower-income countries. The funding will support the range of activities required to develop and manufacture generic versions of the drug.
October 19, 2021 - A World Health Organization-led program to ensure poorer countries get fair access to COVID-19 treatments aims to secure antiviral drugs for patients with mild symptoms for as little as $10 per course, a draft document was seen by Reuters says.
October 19, 2021 - Thailand media reported Yong Poovorawan, chief of the Centre of Excellence in Clinical Virology at Chulalongkorn University, has said that Molnupiravir can help reduce the risk of hospitalization or death among people suffering from Covid-19.
October 18, 2021 - In this JHU this Q&A, Carl Dieffenbach, Ph.D., director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, and Joshua Sharfstein, M.D., talk about the development of the medication, how soon could it be approved, and how it might change the trajectory of the pandemic.
October 14, 2021 - The U.S. Food and Drug Administration announced an upcoming meeting of its Antimicrobial Drugs Advisory Committee (AMDAC) to discuss Merck and Ridgeback's request for an emergency use authorization (EUA) for molnupiravir, an investigational antiviral drug to treat COVID-19. On Nov. 30, the AMDAC will meet to discuss the available data supporting the use of molnupiravir to treat mild-to-moderate COVID-19 in adults who have tested positive for COVID-19 and who are at high risk for progression to severe COVID-19, including hospitalization or death.
October 13, 2021 - STAT News published: This video explains exactly how this drug works in the body to combat the coronavirus.
October 11, 2021 - Merck and Ridgeback Biotherapeutics announced that Merck had submitted an Emergency Use Authorization (EUA) application to the U.S. Food and Drug Administration (FDA) for molnupiravir, an investigational oral antiviral medicine, for the treatment of mild-to-moderate COVID-19 in adults who are at risk for progressing to severe COVID-19 and/or hospitalization.
October 9, 2021 - The journal Nature published: How antiviral pill molnupiravir shot ahead in the COVID drug hunt. Molnupiravir, like remdesivir, is a nucleoside analogue, which means it mimics some of the building blocks of RNA. But the compounds work in entirely different ways.
October 8, 2021 - NDTV reported Aurobindo Pharma Ltd and MSN Laboratories in India plan to continue late-stage trials for Molnupiravir for those with mild COVID-19.
October 7, 2021 - PhilStar reported the Philippines FDA director-general Eric Domingo confirmed four hospitals in Manila had been granted a compassionate special permit to use Molnupiravir to treat their COVID-19 patients.
October 6, 2021 - VOI reported South Korea Prime Minister Kim Boo-kyum said they had secured 20,000 Merck COVID-19 antiviral pills.
October 4, 2021 - The journal BMJ reported: Peter Horby, professor of emerging infectious diseases at the University of Oxford, said, "The proportional reduction in the risk of hospitalization or death is impressive, but it is important to remember that the absolute risks were 14% reduced to 7%, so quite a lot of people need to be treated to prevent one hospitalization or death. This means the drug needs to be very safe and affordable. The safety data also look good, so again this is encouraging." However, he warned, "We need to watch for resistance and think from the outset about the potential role of combination antiviral therapies."
October 1, 2021 - Merck and Ridgeback announced at the Interim Analysis of a Phase 3 study, 7.3 Percent of Patients Who Received Molnupiravir Were Hospitalized Through Day 29, Compared With 14.1 Percent of Placebo-Treated Patients Who were Hospitalized or Died.
September 20, 2021 - BMJ published a Feature Article: The search for antivirals for covid-19. Chris Stokel-Walker asks what has been learned from a similar search nearly 20 years ago. Antivirals are one of the most sought-after, yet missing, tools to control SARS-COV-2.
September 13, 2021 - The journal Nature published: Molnupiravir: coding for catastrophe. Two recently published studies reveal the biochemical and structural bases of how molnupiravir disrupts the fidelity of SARS-CoV-2 genome replication and prevents viral propagation by fostering error accumulation in a process referred to as 'error catastrophe.'
September 13, 2021 - Merck & Co. Inc.'s CEO commented, "We expect to be able to see clinical data here in the back half of the year and still have the potential for an interim analysis and potential for emergency use authorization before year-end," Robert Davis told investors at the Morgan Stanley Global Healthcare Conference, reported MarketWatch.
September 1, 2021 - Merck and Ridgeback Biotherapeutics announces the initiation of Phase 3 MOVe-AHEAD clinical trial (MK-4482-013) (NCT04939428) to evaluate molnupiravir, an investigational oral antiviral therapeutic, for the prevention of COVID-19 infection. The global study enrolls individuals at least 18 years of age and reside in the same household as someone with laboratory-confirmed SARS-CoV-2 infection with symptoms.
August 24, 2021 - Local media in Vietnam reported the first batch of 16,000 doses of Molnupiravir for treatment of COVID-19 patients at home is scheduled to start in HCM City.
August 26, 2021 - The American Society for Biochemistry and Molecular Biology published an article: How an oral antiviral drug confuses the replication machinery of SARS-CoV-2.
August 17, 2021 - The Lung Center of the Philippines and the Quirino Memorial Medical Center are encouraging COVID-19 patients to participate in the clinical trial to test the effectiveness of the antiviral drug Molnupiravir.
August 13, 2021 - Merck announced the initiation of a rolling submission to Health Canada for molnupiravir.
August 10, 2021 - Australia's Therapeutic Goods Administration granted provisional determination to Merck Sharp & Dohme (Australia) Pty Ltd (MSD) concerning Molnupiravir.
July 29, 2021 - Merck (NYSE: MRK) announced financial results for the second quarter of 2021.
July 12, 2021 - Merck and Ridgeback Biotherapeutics announced the previously announced Phase 2 interim results from two Phase 2/3 clinical trials (MOVe-OUT and MOVe-IN) molnupiravir (MK-4482/EIDD-2801). The Phase 3 portion of the global MOVe-OUT trial studying molnupiravir in non-hospitalized adult patients with laboratory-confirmed COVID-19 and at least one risk factor associated with poor disease outcomes is underway.
June 29, 2021 - Pharmaceutical companies in India announced they would collaborate for the clinical trial of Molnupiravir to treat mild Covid-19 in an outpatient setting. These firms include Cipla Limited, Dr. Reddy's Laboratories Ltd, Emcure Pharmaceuticals Limited, Sun Pharmaceutical Industries Limited, and Torrent Pharmaceuticals Limited.
June 9, 2021 - Merck announced it has entered into a procurement agreement with the U.S. government for molnupiravir. Through the agreement, if molnupiravir receives Emergency Use Authorization or Approval by the U.S. FDA, Merck will receive approximately $1.2 billion to supply about 1.7 million courses of molnupiravir to the U.S. government.
June 6, 2021 - Antiviral molnupiravir enters phase 3 clinical trial vs. COVID-19 at Lung Center of the Philippines, reported local media.
May 25, 2021 - MSN Laboratories Pvt. Ltd. confirmed initiating a phase III clinical trial of Molnupiravir capsules to treat Covid-19 in India.
May 18, 2021 - Optimus Pharma announced it received approval from the Drugs Controller General of India to conduct late-stage Phase III clinical trials for Molnupiravir treating COVID-19 patients.
May 11, 2021 - A journal article: Molnupiravir promotes SARS-CoV-2 mutagenesis via the RNA template found 'the biochemical data support a mechanism of action of molnupiravir that is primarily based on RNA mutagenesis mediated via the template strand.'
May 10, 2021 - A University of Alberta virology lab has uncovered how an oral antiviral drug works to attack the SARS-CoV-2 virus, published in the Journal of Biological Chemistry. The researchers demonstrated the underlying mechanism of action by which the antiviral drug molnupiravir changes the viral genome, a process known as excessive mutagenesis or "error catastrophe."
April 27, 2021 - Merck announced that the company has entered into non-exclusive voluntary licensing agreements for molnupiravir with five established Indian generics manufacturers.
April 27, 2021 - Emory University article: Antiviral drug invented by Emory's DRIVE licensed in India for COVID-19 emergency.
April 26, 2021 - India-based Natco Pharma Limited (NSE: NATCOPHARM; BSE: 524816) applied to the Central Drugs Standard Control Organization (CDSCO) in India for approval of Phase-III clinical trial of Molnupiravir Capsules for the treatment of COVID-19 positive patients. NATCO hopes that the CDSCO would give emergency approval of this drug based on "compassionate use" for patients.
April 15, 2021 - Merck announces the discontinuation of MK-7110 to treat hospitalized patients. They are now going to focus their efforts on advancing molnupiravir.
April 2021 - The MIT Libraries published: Progress Toward a Large-Scale Synthesis of Molnupiravir (MK-4482, EIDD-2801) from Cytidine.
March 6, 2021 - Ridgeback Biotherapeutics and Merck Announce Preliminary Findings from a Phase 2a Trial of Investigational COVID-19 Therapeutic Molnupiravir. In addition, the findings reported a secondary objective to reduce the negativity of infectious SARS-CoV-2 virus isolation from nasopharyngeal swabs from participants with symptomatic COVID-19.
February 9, 2021 - Study published by Nature: SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801. 'Our results show that therapeutic and prophylactic administration of EIDD-2801, an oral broad-spectrum antiviral currently in phase II–III clinical trials, dramatically inhibited SARS-CoV-2 replication in vivo and thus has significant potential for the prevention and treatment of COVID-19.'
February 4, 2021 - Merck announced Fourth-Quarter and Full-Year 2020 Financial Results. Merck continued the clinical development of molnupiravir.
December 21, 2020 - The research by scientists at the Institute of Biomedical Sciences, Georgia State University, has been published in Nature Microbiology. And Indian researchers plan to apply to the drug regulator to conduct human trials with the drug.
December 5, 2020 - Researchers in the Institute for Biomedical Sciences at Georgia State University, led by Dr. Richard Plemper, treated a SARS-CoV-2 infection with a new antiviral drug, MK-4482/EIDD-2801 or Molnupiravir, completely suppresses virus transmission within 24 hours.
December 3, 2020 - Study: Therapeutically administered ribonucleoside analog MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. 'We demonstrate high SARS-CoV-2 burden in nasal tissues and secretions, which coincided with efficient transmission through direct contact. Treatment of infected animals with MK-4482/EIDD-2801 twice a day significantly reduced the SARS-CoV-2 load in the upper respiratory tract and completely suppressed spread to untreated contact animals. Thus, this study identified oral MK-4482/EIDD-2801 as a promising antiviral countermeasure to break SARS-CoV-2 community transmission chains.'
August 1, 2020 - Merck & Co. plans to begin two large clinical trials in September 2020 of an experimental oral antiviral therapy for Covid-19, pushing ahead with efforts to bring another treatment option to the market.
July 7, 2020 - Ridgeback Biotherapeutics announced the start of enrollment in a Phase 2 trial of potential COVID-19 treatment EIDD-2801.
July 1, 2020 - Miami-based Ridgeback Biotherapeutics L.P. announced an agreement with Merck that the U.S. Federal Trade Commission granted early termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.
Molnupiravir COVID-19 Oral Antiviral Clinical Trials
The MOVe-AHEAD trial (MK-4482-002) (NCT04575597) was a global Phase 3, randomized, placebo-controlled, double-blind, multi-site study of non-hospitalized adult patients with laboratory-confirmed mild to moderate COVID-19, at least one risk factor associated with poor disease outcomes, and symptom onset within five days before randomization. The primary efficacy objective of MOVe-OUT is to evaluate the efficacy of molnupiravir compared to placebo as assessed by the percentage of participants who are hospitalized and/or die from the time of randomization through Day 29.
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of MK-4482 for the Prevention of COVID-19 (Laboratory-confirmed SARS-CoV-2 Infection With Symptoms) in Adults Residing With a Person With COVID-19. The trial is being conducted globally in countries including Argentina, Brazil, Colombia, France, Guatemala, Hungary, Japan, Mexico, Peru, Philippines, Romania, Russia, South Africa, Spain, Turkey, Ukraine, and the USA.
The companies announced on April 15, 2021, based on a planned interim analysis of data from Phase 2, the dose-finding portion (Part 1) of two ongoing placebo-controlled Phase 2/3 trials evaluating molnupiravir administered twice a day for five days in outpatients (MOVe-OUT) and hospitalized patients (MOVe-IN) with COVID-19, and from a previously completed Phase 2a dose-ranging study in outpatients, the decision has been made to proceed with the Phase 3 portion (Part 2) of MOVe-OUT in outpatients with COVID-19, evaluating the 800 mg dose of molnupiravir twice daily.
Aurobindo Pharma Limited is conducting a Phase 3, Prospective, Open-Label, Randomized, Multicenter, Parallel Study CTRI/2021/08/035424 in India to evaluate the efficacy and safety of Molnupiravir capsules when administered along with Standard of Care compared to Standard of Care alone in Indian patients with Moderate COVID-19 disease.
On June 17, 2021, a non-peer-reviewed study reported Molnupiravir is the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile. Eligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase-polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs. Among 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). On Day 5, the virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups
For more clinical study information, please visit http://merckcovidresearch.com.