Lagevrio (Molnupiravir, Movfor, MK-4482) COVID-19 Oral Antiviral For 2022
Merck's Lagevrio (Molnupiravir) (Molxvir) (emorivir) is an oral antiviral developed initially to treat influenza. Lagevrio 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. Lagevrio is a mutagenic nucleotide analogue, the underlying biochemical mechanisms with the purified RdRp complex of SARS-CoV-2.
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.
Lagevrio consists of the nucleoside analog N4-hydroxycytidine. Lagevrio has been evaluated against coronaviruses, including SARS-1 and MERS-CoV. In addition, Lagevrio s active in several models of SARS-CoV-2, including for prophylaxis, treatment, and prevention of transmission.
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 Lagevrio 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 U.K. 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 13 to 10 to endorse Lagevrio. 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 Lagevrio 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 February 1, 2022, the U.S. NIH issued an updated version of the statement that the COVID-19 Treatment Guidelines Panel for non-hospitalized people released on December 23, 2021. The WHO's ninth update included a conditional recommendation on March 3, 2022, for the treatment with molnupiravir to those at the highest risk of hospitalization and clarified who should not receive this investigational drug.
The NEJM published an Original Research funded by Merck on February 10, 2022 that concluded 'Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19 about 50%. A related Correspondence published by the NEJM on March 16, 2022, stated the efficacy later decreased to approximately 30%.
A WHO published on March 11, 2022, a master study protocol: 'Safety monitoring of molnupiravir for treating mild to moderate COVID-19 infection in low and middle-income countries using cohort event monitoring.' The WHO has provided a conditional recommendation for molnupiravir for those at the highest risk of hospitalization.
On April 1, 2022, the companies announced results from the phase 3 MOVe-OUT clinical trial: for participants with infectious virus isolated at baseline and for whom post-baseline infectivity data were available, molnupiravir was associated with more rapid elimination of infectious virus than placebo. At Day 3 of treatment, among patients with the infectious virus at baseline, infectious SARS-CoV-2 was detected in 0.0% (n=0/92) of patients who received LAGEVRIO, compared with 21.8% (n=20/96) of patients who received placebo. At Day 5, infectious virus was detected in 0.0% (n=0/91) of patients in the LAGEVRIO arm compared with 2.2% (n=2/89) in the placebo arm. And at Day 10, no infectious virus was detected in either arm for patients with the infectious virus at baseline. Molnupiravir was also associated with greater mean reductions from baseline in SARS-CoV-2 RNA than placebo from Days 3 through 10, though molnupiravir and placebo were associated with comparable rates of viral RNA clearance through Day 29.
And the Annals of Internal Medicine, published on June 6, 2022, findings suggest there are additional clinical benefits of molnupiravir beyond the reduction in hospitalization or death. Participants receiving molnupiravir showed faster normalization of CRP and Spo2, with improvements observed on day 3 of therapy, compared with placebo. Molnupiravir-treated participants had a decreased need for respiratory interventions versus placebo-treated participants (relative risk reduction [RRR], 34.3% [95% CI, 4.3% to 54.9%]), with similar findings in participants who were hospitalized after randomization (RRR, 21.3% [CI, 0.2% to 38.0%]). Hospitalized participants who received molnupiravir have discharged a median of 3 days before those who received placebo. Acute care visits (7.2% vs. 10.6%; RRR, 32.1% [CI, 4.4% to 51.7%]) and COVID-19–related acute care visits (6.6% vs. 10.0%; RRR, 33.8% [CI, 5.6% to 53.6%]) were less frequent in molnupiravir- versus placebo-treated participants.
Since December 13, 2021, the ASPR has released about 3,700,000 Molnupiravir doses to U.S. states, territories, and agencies, including (109,876) released on June 21, 2022.
Lagevrio 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.
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 its 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.
Lagevrio Omicron, BA.x sublineages
As of June 2, 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. As does the U.K.'s CoVariants resource.
Merck announced on January 28, 2022, data from six preclinical studies demonstrated molnupiravir was active against the SARS-CoV-2 variant Omicron (B1.1.529) in vitro. And the UK's RECOVERY Trial confirmed testing molnupiravir on January 24, 2022. The oral COVID-19 drug has yet to be evaluated against Omicron in human clinical studies.
On March 1, 2022, the NIH updated the COVID-19 Treatment Guidelines Panel to address the Omicron variant's dominance in the U.S. Department of Health and Human Services' ten regions.
Merck entered into a procurement agreement with the U.S. Government in November 2021. Merck announced it would manufacture 10 million courses of Lagevrio by the end of 2021. In early February 2022, it shipped about 4 million therapy courses to more than 30 markets, including approximately 3.4 million courses to the U.S. Government. 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.
As of June 2022, Merck has shipped molnupiravir to about 30 countries where Molnupiravir (Lagevrio) is authorized: Cyprus, Denmark, Europe, India, Greece, Sri Lanka, Taiwan, USA, Canada, India, Thailand, Australia, Philippines, Singapore, South Africa, South Korea, Vietnam, Japan, Ukraine, Turkey, New Zealand, and the UK. And Merck announced it would 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 is the original generic brand; in Europe and the U.K. (Lagevrio); in India (Molxvir) (Molnulup, Molulife, Molena).
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. The oral antiviral was later acquired by Ridgeback Biotherapeutics, which partnered with Merck & Co. to continue developing the antiviral.
In the U.S. and select markets outside the U.S., LAGEVRIO is the approved trademark for molnupiravir.
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 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 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.
The WHO announced on March 3, 2022, that pregnant and breastfeeding women should not be given the drug. People who take molnupiravir should have a contraceptive plan, and health systems should ensure access to pregnancy testing and contraceptives at the point of care.
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., 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.
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 four days after the final dose. 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 the offspring of treated males have not been completed. The risk beyond three months after the last dose of molnupiravir is unknown.
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.
Lagevrio Side Effects
There are limited clinical data available for molnupiravir. No contraindications have been identified based on the limited available data on the emergency use of molnupiravir authorized under its EUA. Serious and unexpected adverse events may occur that have not been previously reported with molnupiravir use. In 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 about the potential risk of molnupiravir-induced tumorigenesis and the emergence of detrimental mutations in sperm precursor cell generation and embryo development.
On January 5, 2022, Indian Council for Medical Research (ICMR) Chief Dr. Balram Bhargava said 'that 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.
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/per patient. This price equals 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.
Lagevrio 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 administer COVID-19 products once they become available. CMS identified specific code(s) for each COVID-19 product for Medicare payment.
On April 28, 2022, New Jersey-based Merck Inc. announced LAGEVRIO sales were $3.2 Billion in the first quarter of 2022. For the full year, Merck forecasts molnupiravir revenues up to $5.5 billion.
Merck & Co. announced on February 3, 2022, that sales of Molnupiravir were $952 million in the fourth quarter of 2021, primarily consisting of sales in the U.S., the U.K., and Japan. Merck expects up to $6 billion in molnupiravir sales in 2022. Merck shares the profits equally with Ridgeback Biotherapeutics.
Lagevrio News For 2021 - 2022
June 7, 2022 - Merck and Ridgeback Biotherapeutics announced the Annals of Internal Medicine published additional data from the Phase 3 MOVe-OUT trial evaluating LAGEVRIO™. Conclusion: The findings suggest there are additional important clinical benefits of molnupiravir beyond the reduction in hospitalization or death. “The analyses add to our understanding of the clinical profile of LAGEVRIO and help to reinforce the importance of LAGEVRIO as part of the response to the COVID-19 pandemic,” said Dr. Dean Y. Li, president of Merck Research Laboratories.
May 10, 2022 - ICER Independent appraisal committee votes 11-2 that the evidence is not adequate to demonstrate a net health benefit for molnupiravir over symptomatic care alone.
April 26, 2022 - The BMJ published: Merck’s Move-Out trial of molnupiravir raises important concerns about the approval of molnupiravir to treat outpatients with covid-19 in the United Kingdom. Molnupiravir has not yet been approved in Europe.
April 16, 2022 - The Singapore Health Sciences Authority approved molnupravir to treat adult COVID-19 patients.
April 6, 2022 - The San Francisco Chronicle reported about 3,500 doses of unused, no-cost, COVID-19 oral antivirals are being returned.
April 1, 2022 - Merck and Ridgeback Biotherapeutics announced that data evaluating LAGEVRIO™(molnupiravir) would be presented at the 2022 European Congress of Clinical Microbiology & Infectious Diseases Abstract #4514.
March 24, 2022 - Time published an article: Why You Still Can’t Just Walk Into a Pharmacy and Get a Prescription for a COVID-19 Pill.
March 18, 2022 - The Scoop reported Molnupiravir distribution would be limited as not all individuals are eligible, according to Brinui's deputy permanent secretary of health, Dr. Ang Swee Hui.
March 18, 2022 - Local media reported a Thailand medical expert urged the government to switch from favipiravir to molnupiravir as Thailand now plans to declare Covid-19 endemic.
March 10, 2022 - Local media reported Cyprus Deputy head of pharmaceutical services Elena Panagiotopoulou stated the anti-Covid oral pill Molnupiravir /Lagevrio 200mg had been administered to 984 patients, and only 7% of them had to be admitted to the hospital.
March 3, 2022 - The WHO updated its treatment guidelines to include molnupiravir. Because of concerns and data gaps, molnupiravir should be provided only to non-severe COVID-19 patients with the highest risk of hospitalization. These are typically people who have not received a COVID-19 vaccination, older people, people with immunodeficiencies, and people living with chronic diseases.
March 3, 2022 - The BMJ published an Editorial written by [email protected] - Molnupiravir’s authorization was premature.
February 19, 2022 - India-based media reported Hetero Pharma announced positive results of Phase III trials of Movfor (Molnupiravir). The results, presented as an Oral Abstract at the Conference on Retroviruses and Opportunistic Infections demonstrated that Molnupiravir along with the standard of care (SOC) reduced the risk of hospitalization by over 65% compared to SOC alone.
February 16, 2022 - Local media reported: “Molnupiravir could be useful in non-pregnant unvaccinated adults with Covid-19 at increased risk of severity, including hospitalization,” said Awadesh Singh at the GD Hospital and Diabetes Institute, Calcutta, India, and his co-reviewers wrote in the medical journal Diabetes and Metabolic Syndrome: Clinical Research and Reviews.
February 4, 2022 - Anadolu Agency reported Turkey would soon administer molnupiravir to coronavirus patients, according to Professor Alper Şener, a member of the Health Ministry’s Coronavirus Scientific Advisory Board.
January 28, 2022 - Merck issued a press release stating: “These findings from multiple independent in vitro studies showing that molnupiravir has consistent antiviral activity against Omicron, the primary variant circulating globally, provide additional confidence in the potential of molnupiravir as an important treatment option for certain adults with mild to moderate COVID-19 who are at high risk for progressing to severe disease,” said Dr. Dean Y. Li, president, Merck Research Laboratories. The in vitro studies were independently conducted in Belgium, the Czech Republic, Germany, Poland, the Netherlands, and the U.S.
January 24, 2022 - The RECOVERY Trial announced it would begin testing molnupiravir. The study is open to all patients hospitalized with severe COVID-19 and the study is taking place in 177 NHS hospital sites across the UK.
January 20, 2022 - The Medicines Patent Pool announced today that it had 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 12, 2022 - In its second warning against the use of Molnupiravir, the Indian Council of Medical Research stated the harms of the antiviral pill far outweigh its benefits, reported local media.
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. It added that the drug is yet to be evaluated against Omicron in clinical studies.
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 would 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 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 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
Merck announced on April 1, 2022, a presentation includes final analyses evaluating virologic outcomes throughout and following a five-day course of LAGEVRIO as part of the Phase 3 MOVe-OUT trial, which studied LAGEVRIO versus placebo for the treatment of COVID-19 in non-hospitalized adults with mild to moderate COVID-19 who were at high risk for progressing to severe disease. Among study participants for whom samples were available, viral infectivity was assessed via a plaque-forming assay in Vero cells. Prespecified exploratory virologic outcomes included changes from baseline in SARS-CoV-2 RNA levels and the percentage of study participants with viral clearance (i.e., undetectable SARS-CoV-2 RNA) and undetectable infectious SARS-CoV-2 through Day 29 in the modified intent-to-treat (mITT) population (≥1 dose of study intervention and not hospitalized prior to first dose). In participants with infectious virus isolated at baseline and for whom post-baseline infectivity data were available, molnupiravir was associated with more rapid elimination of infectious virus than placebo. At Day 3 of treatment, among patients with infectious virus at baseline, infectious SARS-CoV-2 was detected in 0.0% (n=0/92) of patients who received LAGEVRIO, compared with 21.8% (n=20/96) of patients who received placebo. At Day 5, infectious virus was detected in 0.0% (n=0/91) of patients in the LAGEVRIO arm compared with 2.2% (n=2/89) in the placebo arm. At Day 10, no infectious virus was detected in either arm for patients with infectious virus at baseline. Molnupiravir was also associated with greater mean reductions from baseline in SARS-CoV-2 RNA than placebo from Days 3 through 10, though molnupiravir and placebo were associated with comparable rates of viral RNA clearance through Day 29.
On January 24, 2022, the UK's RECOVERY Trial confirmed that Molnupiravir would be investigated as a potential treatment for patients hospitalized with COVID-19. RECOVERY will compare molnupiravir (800 mg twice daily for five days) with the usual standard of hospital care in adult patients who are hospitalized because of COVID-19. Molnupiravir is also being investigated as an at-home treatment by the PANORAMIC Trial, led by Oxford University's Nuffield Department of Primary Care Health Sciences.
The MOVe-AHEAD trial (MK-4482-002) (NCT04575597) found early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19. Merck Sharp and Dohme funded the MOVe-OUT study. 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.