Molnupiravir Antiviral Description
Molnupiravir (MK-4482, EIDD-2801) is an experimental oral antiviral developed initially to treat influenza at Emory University. 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.
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.
In July 2021, a study focused on how Molnupiravir promotes SARS-CoV-2 mutagenesis via the RNA template. Preclinical data in cell culture revealed a dose-dependent increase in G to A and C to U transition mutations that correlated with increases in antiviral effects against coronaviruses. Molnupiravir is therefore classified as a mutagenic nucleotide analogue. Here we studied the underlying biochemical mechanisms with the purified RdRp complex of SARS-CoV-2. Based on our data, we developed a model that describes effects on both efficiency and fidelity of RNA synthesis.
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' totality indicates that molnupiravir is not mutagenic or genotoxic in vivo mammalian systems.
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. In addition, Merck plans to initiate a clinical program to evaluate molnupiravir for post-exposure prophylaxis in the second half of 2021.
"These data are promising, and we are pleased to be able to present the Phase 2 interim results for molnupiravir while we proceed with the Phase 3 portion of MOVe-OUT in non-hospitalized patients," said Wendy Holman, CEO, Ridgeback Biotherapeutics, in a press statement issued on Jul 12, 2021. "There remains a great need for a range of solutions for the pandemic, and we are hopeful that molnupiravir will play a role in helping patients."
"As the (COVID-19) pandemic continues to evolve and surges are being reported in many places around the world, it is important that we investigate new ways to protect individuals exposed to the (SARS-CoV-2) virus from becoming infected with symptomatic disease," said Dr. Nick Kartsonis, SVP, vaccines, and infectious diseases, clinical research, Merck Research Laboratories, in a press statement issued on September 1, 2021.
The MOVe-AHEAD study is a Phase 3 multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating the efficacy and safety of orally administered molnupiravir compared to placebo in preventing the spread of SARS-CoV-2, the virus that causes COVID-19, within households. Last updated on October 1, 2021.
Merck confirmed plans on October 1, 2021, to seek Emergency Use Authorization in the U.S.and regulatory agencies worldwide. If Authorized, Molnupiravir could be the first oral antiviral medicine for COVID-19.
Molnupiravir [USAN] RN: 2349386-89-4. UNII: YA84KI1VEW, InChIKey: HTNPEHXGEKVIHG-QCNRFFRDSA-N; PubChem CID145996610; CAS Number 2349386-89-4; DrugBank DB15661; Chemical Formula: C13H19N3O7; Molecular Formula: C13H19N3O7; CHEBI: 180653
Molnupiravir Antiviral History
Molnupiravir was originally 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. It was later acquired by Ridgeback Biotherapeutics, which partnered with Merck & Co. to continue developing the antiviral.
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 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. The Phase 2a randomized, placebo-controlled, double-blinded clinical trial of EIDD-2801 in adult men and women tested positive for SARS-CoV-2 infection within 144 hours of polymerase chain reaction confirmation and were hospitalized with a diagnosis of COVID-19. Rapid enrollment and treatment will be initiated such that the first dose of EIDD-2801 or placebo will be administered as soon as possible and within seven days of onset of symptoms.
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.
On January 25, 2021, Merck stated that Molnupiravir is currently being evaluated in Phase 2/3 clinical trials in hospital and outpatient settings. The primary completion date for the Phase 2/3 studies is May 2021. The company anticipates initial efficacy data in the first quarter of 2021, which Merck plans to share publicly if clinically meaningful.
On March 6, 2021, Merck and Ridgeback Biotherapeutics announced preliminary results from the Phase 2a study evaluating the safety, tolerability, and efficacy to eliminate SARS-CoV-2 viral RNA of molnupiravir. Of the 182 participants with an evaluable nasopharyngeal swab, 42% (78/182) showed detectable levels of cultured virus at baseline. The companies also reported findings on one secondary objective from the Phase 2a study, showing a reduction in time (days) to the negativity of infectious virus isolation in nasopharyngeal swabs from participants with symptomatic SARS-CoV-2 infection, as determined by isolation in Vero cell line culture. On day 5, there was a reduction (nominal p=0.001, not controlled for multiplicity) in positive viral culture in subjects who received molnupiravir (all doses) compared to placebo: 0% (0/47) for molnupiravir and 24% (6/25) for placebo.
"We are very pleased to share our initial Phase 2 infectivity data at this important conference, which remains at the forefront for critical clinical scientific information in infectious diseases," shared Dr. Wendy Painter, Chief Medical Officer of Ridgeback Biotherapeutics, in a press release. "We continue to make progress in our Phase 2/3 clinical programs evaluating molnupiravir in both outpatient and hospital settings and plan to provide updates when appropriate," added Dr. Roy Baynes, SVP and head of global clinical development CMO, Merck Research Laboratories.
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.'
"To advance a drug quickly and across the globe in all the countries where it is needed, you need the capacity of a company like Merck," said George Painter, Ph.D., CEO of the non-profit Emory-owned DRIVE, at a media briefing on April 27, 2021. "It's gratifying to see how quickly they moved and how they're getting this into the hands of people in India to meet this threat."
Wendy Holman, CEO, Ridgeback Biotherapeutics, said in a related press release, "We are pleased that molnupiravir continues to show promise as a potential treatment for non-hospitalized patients with COVID-19. Data from Ridgeback Bio's EIDD-2801-2003 study (MK-4482-006) coupled with Merck's MK-4482-002 study provides compelling evidence of molnupiravir's antiviral. We look forward to the initiation and completion of the Phase 3 portion of the MOVe-OUT study."
On June 9, 2021, Merck confirmed in a press statement 'it plans to submit applications for emergency use or approval to regulatory bodies outside of the USA and is currently in discussions with other countries interested in advance purchase agreements for molnupiravir. Merck is committed to providing timely access to molnupiravir globally. As part of its access strategy, Merck has also entered into non-exclusive voluntary licensing agreements for molnupiravir with established generic manufacturers to accelerate the availability of molnupiravir in 104 low- and middle-income countries following approvals or authorization by regulatory agencies.
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.'
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.
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 Antiviral Indication
Molnupiravir (MK-4482/EIDD-2801) antiviral is indicated to mitigate SARS-CoV-2 betacoronavirus infection and block transmission, preventing COVID-19 disease.
The U.S. NIH updated Therapeutic Management of Nonhospitalized Adults With COVID-19 on September 24, 2021.
Molnupiravir Antiviral Use With SARS-CoV-2 Virus Variants
Pre-clinical and clinical data have shown molnupiravir to be active against the most common SARS-CoV-2 variants.
A Merck spokesperson said in a statement to The Hill on September 29, 2021, "As emerging variants worsen the COVID-19 pandemic across the globe, we must evaluate potential treatments with these variants in mind. These in-vitro data suggest that molnupiravir is effective against SARS-CoV-2 variants, particularly when initiated early in the course of illness. Jay Grobler, head of infectious disease and vaccines at Merck, said at the conference Wednesday, "It's a really nice observation because it gives us confidence that it will work the same across the variants that are already out there, and potentially against any new variants that may emerge," Bloomberg reported.
Molnupiravir Antiviral Side Effects
May 2020 - Former Head of U.S. Biomedical Advanced Research and Development Authority Rick Bright wrote that “similar experimental drugs in this class had been shown to cause reproductive toxicity in animals."
May 2021 - β-D-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells.
A non-peer-reviewed phase 2 study results published on June 17, 2021, found Molnupiravir and placebo were associated with few, and mainly low-grade, adverse events. The incidence of treatment-associated adverse events was lowest in the molnupiravir 800 mg group. The only adverse events reported by more than 4 participants were headache, insomnia, and increased alanine aminotransferase. Two (1.4%) adverse events led to discontinuation of molnupiravir compared with 1 (1.6%) for placebo. Grade 3 or higher adverse events occurred in 5.0% and 8.1% in the molnupiravir and placebo groups, respectively. There were no treatment- or dose-related trends in hematology or clinical chemistry data during the study. And, four serious adverse events occurred and resulted in hospitalization, comprising one (1.6%) participant administered placebo who had hypoxia, two (3.2%) participants administered 400 mg molnupiravir (cerebrovascular accident and decreased oxygen saturation), and one (1.8%) participant administered 800 mg molnupiravir who had an acute respiratory failure. Treatment was discontinued in all 4 participants.
July 2021 - 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.
University of North Carolina researchers published a study in The Journal of Infectious Diseases on August 1, 2021, where they exposed 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.
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Molnupiravir Antiviral Availability
As of October 11, 2021, Merck confirmed it has been producing molnupiravir at risk and expects to produce 10 million courses of treatment by the end of 2021, with more courses expected to be produced in 2022. The U.S. NIH Updated COVID-19 Treatment Guidelines Panel’s Statement on the Prioritization of Anti-SARS-CoV-2 Monoclonal Antibodies for the Treatment or Prevention of SARS-CoV-2 Infection When There Are Logistical or Supply Constraints, on October 7, 2021.
On October 12, 2021, Everest Organics confirmed it is producing ingredients for Merck's Molnupiravir Covid-19 treatment pill. Divi's Laboratories is also an API produced for Merck's experimental oral drug.
As of October 13, 2021, the Molnupiravir antiviral is available in the USA, Canada - pending, UK - pending, India - pending; Thailand - pending, Australia, Philippines, Singapore, South Korea, and Vietnam.
Molnupiravir Antiviral Pricing
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 US government has already ordered 1.7 million treatment courses, at about $700/patient. This price is equal to 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 US price would be equal to about 161 times the estimated sustainable generic price.
Molnupiravir Antiviral News
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 has 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. “The extraordinary impact of this pandemic demands that we move with unprecedented urgency, and that is what our teams have done by submitting this application for molnupiravir to the FDA within 10 days of receiving the data,” said Robert M. Davis, chief executive officer and president, Merck.
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 have 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 have secured 20,000 Merck COVID-19 antiviral pills.
October 6, 2021 - Reuters reported Merck signed with Singapore to provide its COVID-19 antiviral pill. Update: Yahoo News Singapore's media queries, the Ministry of Health confirmed that it had signed an agreement with MSD Pharma (Singapore) to purchase the drug which will be available for use after MSD obtains authorization for use in Singapore.
October 4, 2021 - Local media reported the Thailand government is in talks with Merck & Co to purchase 200,000 courses of the company's experimental COVID-19 pill.
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. Merck Plans to Seek Emergency Use Authorization in the U.S. as Soon as Possible and to Submit Applications to Regulatory Agencies Worldwide. If Authorized, Molnupiravir Could be the First Oral Antiviral Medicine for COVID-19.
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 (NYSE: MRK) and Ridgeback Biotherapeutics announce 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 resides 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 (LCP) 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. The hospitals need a total of 35 patients. The LCP has already recruited 15 patients, and it needs 10 more participants, while the QMMC needs 10 participants.
August 13, 2021 - Merck announced the initiation of a rolling submission to Health Canada for molnupiravir.
August 10, 2021 - The Therapeutic Goods Administration granted provisional determination to Merck Sharp & Dohme (Australia) Pty Ltd (MSD) in relation to 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), an investigational oral antiviral therapeutic. The data were presented during the late-breaking clinical trials session at the European Congress of Clinical Microbiology & Infectious Diseases. 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. In addition, Merck plans to initiate a clinical program to evaluate molnupiravir for post-exposure prophylaxis in the second half of 2021. "These data are promising, and we are pleased to be able to present the Phase 2 interim results for molnupiravir while we proceed with the Phase 3 portion of MOVe-OUT in non-hospitalized patients," said Wendy Holman, CEO, Ridgeback.
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 approximately 1.7 million courses of molnupiravir to the U.S. government. Merck has been investing at risk to scale up production of molnupiravir and expects to have more than 10 million courses of therapy available by the end of 2021.
June 6, 2021 - Antiviral molnupiravir enters phase 3 clinical trial vs. COVID-19 at Lung Center of the Philippines, reported local media. Among those qualified to be included in the trial are symptomatic patients who tested positive within the past five days, aged 18 and above, and have yet to be vaccinated.
May 25, 2021 - MSN Laboratories Pvt. Ltd. confirmed it is initiating a phase III clinical trial of Molnupiravir capsules to treat Covid-19 in India, with about 2,400 subjects suffering from mild-to-moderate Covid-19.
May 25, 2021 - Hyderabad- based Optimus Pharma stated, "Optimus is all geared to immediately begin clinical trials on Molnupiravir on COVID-19 patients in India. The clinical trial will let us know the efficacy of this molecule on COVID-19 patients," Chairman & Managing Director Dr. D Srinivas Reddy said.
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. Today's Optimus group employs directly about 950 people and provides indirect employment to about 600 across the group.
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." "The polymerase, or replication engine of the virus, mistakes molnupiravir molecules for the natural building blocks required for viral genome replication and mixes them in," explained Matthias Götte, professor and chair of the Department of Medical Microbiology & Immunology in the Faculty of Medicine & Dentistry and member of the Li Ka Shing Institute of Virology.
April 27, 2021 - Merck announced that the company has entered into non-exclusive voluntary licensing agreements for molnupiravir with five established Indian generics manufacturers. Merck entered into these agreements to accelerate the availability of molnupiravir in India and other low- and middle-income countries following approvals or emergency authorization by local regulatory agencies.
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. The company said it is ready to launch the product this month if approval is given.
April 26, 2021 - BMJ article: The U.K. government has launched an Antivirals Taskforce to identify treatments to be used at home by people who test positive for SARS-CoV-2 infection to stop the virus from spreading and speed up recovery time. The government's chief scientific adviser, Patrick Vallance, said, "Antivirals in tablet form are another key tool for responding. They could help protect those not protected by or ineligible for vaccines. They could also be another layer of defense in the face of new variants of concern. The task force will help ensure the most promising antivirals are available for deployment as quickly as possible."
April 15, 2021 - As Merck announces the discontinuation of MK-7110 to treat hospitalized patients, they are now going to focus their efforts on advancing molnupiravir. "Merck's commitment from the outset of the pandemic has been to deploy our expertise and capabilities where they can have the most impact," said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.
April 2021 - The MIT Libraries published: Progress Toward a Large-Scale Synthesis of Molnupiravir (MK-4482, EIDD-2801) from Cytidine.
March 8, 2021 - Study results: Early antiviral treatment in outpatients with COVID-19 (FLARE): a structured summary of a study protocol for a randomized controlled trial.
March 6, 2021 - Ridgeback Biotherapeutics and Merck Announce Preliminary Findings from a Phase 2a Trial of Investigational COVID-19 Therapeutic Molnupiravir. 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, an orally available antiviral candidate for the treatment of COVID-19, in collaboration with Ridgeback Biotherapeutics L.P. It is currently being evaluated in Phase 2/3 clinical trials in both the hospital and outpatient settings. The primary completion date for the Phase 2/3 studies is May 2021. The company anticipates interim efficacy data in the first quarter of 2021.
January 25, 2021 - Merck announced that the company plans to focus its SARS-CoV-2 / COVID-19 research strategy and production capabilities on advancing two therapeutic candidates, MK-4482 MK-7110. Merck stated in a press release it also continues to evaluate the potential of the measles-virus vector and vesicular stomatitis virus vector-based platforms and pursues broader pandemic-response capabilities.
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. The antiviral drug Molnupiravir, or MK-4482/EIDD-2801, is taken orally. Molnupiravir is being developed by the biotechnology firm Ridgeback Biotherapeutics in collaboration with the pharmaceutical firm Merck.
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 of an experimental oral antiviral therapy for Covid-19, pushing ahead with efforts to bring another treatment option to the market. There is a "profound medical need for an orally active treatment," Roger Perlmutter, the pharmaceutical giant's top scientist, said Friday on Merck's earnings conference call. The therapy, known as MK-4482.
July 7, 2020 - Ridgeback Biotherapeutics announced the start of enrollment in a Phase 2 trial of potential COVID-19 treatment EIDD-2801. The new trial will be conducted using the new COVID-19 drug testing platform, AGILE. AGILE will test multiple potential therapeutics, and EIDD-2801 was selected to be the first oral antiviral to be studied in the AGILE platform.
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. 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.
Molnupiravir 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 prior to 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, was last updated on October 1, 2021. 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.