Merck Sharp and Dohme (MSD) developed molnupiravir in collaboration with Ridgeback Biotherapeutics.
“Molnupiravir is the oral prodrug of beta-D-N4-hydroxycytidine (NHC), a ribonucleoside that has shown antiviral activity against SARS-CoV-2 in vitro and in clinical trials. NHC uptake by viral RNA-dependent RNA-polymerases results in viral mutations and lethal mutagenesis.” – REF
LAGEVRIO (molnupiravir) (MK-4482) is an investigational, orally administered nucleoside analog that inhibits the replication of SARS-CoV-2. It is a prodrug of beta-D-N4-hydroxycytidine (NHC), a ribonucleoside that has shown antiviral activity against SARS-CoV-2 in vitro and in clinical trials. NHC uptake by viral RNA-dependent RNA-polymerases results in viral mutations and lethal mutagenesis.” – REF
Interim phase III trial results, released by MSD via press release on October 1, 2021 conclude molnupiravir reduced the risk of admission to hospital or death by around 50% in non-hospitalised adults who had mild to moderate COVID-19 and were at risk of poor outcomes.
The Phase 3 clinical trial, referred to as the MOVe-OUT study, looked at the “treatment of non-hospitalized patients with laboratory-confirmed COVID-19 and at least one risk factor associated with poor disease outcomes”.
On November 4, 2021, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) was the first to authorise molnupiravir with the trade name Lagevrio, for the treatment of mild to moderate COVID-19 in adults with at least one risk factor for severe illness. The reasoning being to reduce symptom severity and ease pressure on the National Health Service over winter.
- Merck’s Molnupiravir – WEBSITE
- Merck’s product pipeline – HERE
- NIH Therapeutic Management of Non-hospitalized Adults With COVID-19 – READ, ARCHIVE
- Running analysis of all Molnupiravir studies for COVID-19 – HERE
Molnupiravir links in reverse chronological order
2023
July 3, 2023 – BMJ Open: Platform adaptive trial of novel antivirals for early treatment of COVID-19 In the community (PANORAMIC): protocol for a randomised, controlled, open-label, adaptive platform trial of community novel antiviral treatment of COVID-19 in people at increased risk of more severe disease – Gbinige and Chris Butler et al – READ, CV19 analysis – READ, Prof Butler was also chief investigator for ivermectin trial, comment by Dr Kory – HERE
2022
December 22, 2022 – The Lancet: Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial – Christopher Butler et al – READ, CREDIT
- Amazingly high enrolment with “26,411 patient RCT in the UK, showing faster recovery but no significant difference in hospitalization/death or transmission. Improved recovery may be in part due to the open label design with self-reported symptomatic data. Viral load initially declined more quickly, but was higher at 14 days.” – CV19 analysis – READ
October 17, 2022 – SSRN Pre-Print: Molnupiravir Plus Usual Care Versus Usual Care Alone as Early Treatment for Adults with COVID-19 at Increased Risk of Adverse Outcomes (PANORAMIC): Preliminary Analysis from the United Kingdom Randomised, Controlled Open-Label, Platform Adaptive Trial by Butler et al – READ, PDF
October 11, 2022 – MedPage: Authorized COVID Antiviral Fails to Cut Hospitalization Risk — Recovery moderately faster with molnupiravir, but risks may outweigh benefit – READ
October 11, 2022 – BMJ: Covid-19: Antiviral purchased by UK government does not lower risk of hospital admission, trial shows by Jacqui Wise – READ
- “Molnupiravir, a covid-19 antiviral drug bought by the UK government in the amount of 2.23 million doses, is no better than placebo at lowering the risks of death and hospital admission, a pivotal UK trial has found.”
October 8, 2022 – Observational Study not randomised: Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalisation, and in-hospital outcomes among community-dwelling, ambulatory patients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study by Wong et al – READ
October 6, 2022 – Merck PRESS RELEASE: Merck and Ridgeback Biotherapeutics Provide Update on New Clinical and Non-Clinical Studies of LAGEVRIO™ (molnupiravir) – READ
September 25, 2022 – UK NHS – COVID-19 Therapeutics: Antivirals and neutralising-monoclonal antibodies (AVs and nMABs): Non-hospitalised treatments – NATIONAL SUMMARY – EXCEL, ARCHIVE
- “Only 13 944 of the UK’s 2.23 million doses of molnupiravir have been administered outside clinical trials in the UK, according to NHS data up to the week ending 25 September 2022” – REF
- “The NHS has used less than 1% of the antiviral treatments it ordered, and it is not clear how the other 99% will be used before they pass their expiry dates,” said Hill.
August 2022 – Annals of Internal Medicine: Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19 – A Randomized, Placebo-Controlled Trial by Johnson et al – READ
June 7, 2022 – Merck PRESS REALEASE: Merck and Ridgeback Announce New Data For Investigational LAGEVRIO™ (molnupiravir) From Phase 3 MOVe-OUT Study – READ
April 1, 2022 – Merck PRESS RELEASE: Merck and Ridgeback to Present Data Demonstrating That Treatment With LAGEVRIO™ (molnupiravir) Was Associated With More Rapid Elimination of Infectious SARS-CoV-2 Than Placebo – READ
March 31, 2022 – Update on Progress of LAGEVRIO™ (molnupiravir) Supply and Access Strategy – PDF
As of March 31, 2022, we have committed to providing approximately 10 million courses of LAGEVRIO™ (molnupiravir) through nearly 40 supply and purchase agreements.
March 9, 2022 – The Conversation: Molnupiravir: why are there potential safety issues around this COVID antiviral? – READ
February 8, 2022 – TGA Regulatory Decision Notice: Australian Public Assessment Report (AusPAR): Molnupiravir- ARCHIVE
February 24, 2022 – NIH COVID-19 Treatment Guidelines – Molnupiravir – READ, ARCHIVE
Feburary 19, 2022 – Merck PRESS RELEASE: Merck and Ridgeback Statement on Clinical Trial of Hetero’s Generic Molnupiravir – In India a Global Efforts to Accelerate Access to Molnupiravir – READ – July 2021 clinical trial in india – READ
February 10, 2022 – NEJM: Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients – Bernal et al – (MOVeOUT study group) – READ
February 8, 2022 – Merck PRESS RELEASE: Merck and Ridgeback Announce That 3.1 Million Courses of Molnupiravir, an Investigational Oral Antiviral COVID-19 Medicine, Have Been Supplied to the U.S. Government for Use in the United States – READ
February 3, 2022 – Merck PRESS RELEASE: Merck Announces Fourth-Quarter and Full-Year 2021 Financial Results – READ
- “Merck will have shipped more than 4 million courses of therapy to more than 25 countries, including approximately 3 million courses to the U.S. Government as part of its procurement agreement.”
January 28, 2022 – Merck PRESS RELEASE: Merck and Ridgeback’s Molnupiravir, an Investigational Oral Antiviral COVID-19 Medicine, Demonstrated Activity Against Omicron Variant in In Vitro Studies – READ
January 20, 2022 – TGA: TGA provisionally approves two oral COVID-19 treatments, molnupiravir (LAGEVRIO) and nirmatrelvir + ritonavir (PAXLOVID) – READ
January 18, 2022 – TGA provisionally approves Merck Sharp & Dohme (Australia) Pty Ltd’s oral COVID-19 treatment, LAGEVRIO (molnupiravir) – READ, TGA Documents molnupiravir – READ
January 18, 2022 – Merck PRESS RELEASE”: Merck and Ridgeback Announce Supply Agreement with UNICEF for Molnupiravir – READ
2021
December 30, 2021 – NIH: The COVID-19 Treatment Guidelines Panel’s Statement on Therapies for High-Risk, Nonhospitalized Patients With Mild to Moderate COVID-19 – ARCHIVE
- “As a mutagenic ribonucleoside antiviral agent, there is a theoretical risk that molnupiravir will be metabolized by the human host cell and incorporated into the host DNA, leading to mutations”
- “The FDA concluded that, based on the available genotoxicity data and the 5-day duration of treatment, molnupiravir has a low risk for genotoxicity.”
- “In the MOVe-OUT trial, molnupiravir reduced the rate of hospitalization or death by 30% compared to placebo.”
December 24, 2021 – Merck PRESS RELEASE: Merck and Ridgeback’s Molnupiravir, an Investigational Oral Antiviral COVID-19 Treatment, Receives Special Approval for Emergency in Japan – READ
December 23, 2021 – Merck PRESS RELEASE: Merck and Ridgeback’s Molnupiravir Receives U.S. FDA Emergency Use Authorization for the Treatment of High-Risk Adults With Mild to Moderate COVID-19 – READ, FDA Fact Sheet – PDF, Merck Fact Sheet – READ
December 23, 2021 – FDA NEWS RELEASE: Coronavirus (COVID-19) Update: FDA Authorizes Additional Oral Antiviral for Treatment of COVID-19 in Certain Adults – READ,
FDA FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR MOLNUPIRAVIR – PDF
December 22, 2021 – Fox News: Ingraham Angle: Dr Stephen Smith and Dr Harvey Risch – 10 of the review committee on molmupiravir voted it down. This is a drug that makes the virus mutate like crazy and could create mutant strains across the world – ARCHIVE
December 22, 2021 – Merck PRESS RELEASE: Merck and Ridgeback Announce U.K. Government to Purchase Additional 1.75 Million Courses of Molnupiravir – READ
December 16, 2021 – Merck PRESS RELEASE: Merck and Ridgeback Announce Publication of Phase 3 Study of Molnupiravir, an Investigational Oral Antiviral COVID-19 Treatment, in the New England Journal of Medicine – READ
fully published Feb 10, 2022 – STUDY
November 17, 2021 – Merck PRESS RELEASE: Merck and Ridgeback to Present Phase 3 Data for Molnupiravir, an Investigational Oral COVID-19 Antiviral Medicine, at American Society of Tropical Medicine and Hygiene (ASTMH) 2021 Annual Meeting – READ
November 4, 2021 – BMJ: Covid-19: UK becomes first country to authorise antiviral molnupiravir – ” temporary authorisation” – READ
November 4, 2021 – Merck PRESS RELEASE: Merck and Ridgeback’s Molnupiravir, an Oral COVID-19 Antiviral Medicine, Receives First Authorization in the World – READ
November 4, 2021 – UK’s MHPA: Regulatory approval of Lagevrio (molnupiravir) – READ
November 4, 2021 – UK MHRA PRESS RELEASE: First oral antiviral for COVID-19, Lagevrio (molnupiravir), approved by MHRA – The antiviral was found to be safe and effective following a stringent review of the available evidence – READ
October 25, 2021 – BMJ: Covid-19: UK stockpiles two unapproved antiviral drugs for treatment at home – Molnupiravir & PF-07321332/ritonavir (Paxlovid) – READ
October 25, 2021 – Merck PRESS RELEASE: Merck and Ridgeback Announce Initiation of a Rolling Review by the European Medicines Agency for Molnupiravir – READ
October 11, 2021 – Merck PRESS RELEASE: Merck and Ridgeback Announce Submission of Emergency Use Authorization Application to the U.S. FDA for Molnupiravir… Submissions to Regulatory Agencies Worldwide Underway – READ
October 7, 2021 – TK News by Matt Taibbi Substack: The Cult of the Vaccine – The tone of the coverage on molnupiravir turned within a day – READ, WATCH
- i.e. NY Times & Fauci – “A pill that could potentially treat Covid-19 is a ‘game-changer,’ but experts are emphasizing that it’s not an alternative to vaccinations.” – WATCH
October 5, 2021 – Dr James Lyons-Weiler Substack: The Extraordinary Hypocrisy of Molnupiravir – The Representation of Merck’s Molnupiravir as a “Game Changer” Only Underscores a Bias – And Merck Has Other Data It Is Not Sharing – READ
- “Merck and NIH allowed 14.1% of people in the control arms to develop severe COVID-19 and die with no treatment. None. Just placebo. How did the NIH and the FDA let this happen in the face of the evidence of efficacy of early treatment? How could they?”
October 4, 2021 – News: Brand new oral Covid-19 treatment bound for Australian shores – Australians will soon have access to a brand new Covid treatment after Scott Morrison announced the purchase of 300,000 courses of the new drug – Molnupiravir – READ
October 4, 2021 – BMJ: Covid-19: Molnupiravir reduces risk of hospital admission or death by 50% in patients at risk, MSD reports – READ
October 2, 2021 – CNN: Covid-19 antiviral pill could be a game changer, but vaccines are still America’s way out of the pandemic, experts say – READ
October 1, 2021 – Associated Press: Merck Antiviral Pill’s Clinical Trial Success Is ‘Good News,’ Fauci Says – but stressed that vaccines remained the best tool to prevent infections. – WATCH
October 1, 2021 – NPR: A pill can reduce deaths by half in new coronavirus patients, company says – READ
October 1, 2021 – Merck PRESS RELEASE: Merck and Ridgeback’s Investigational Oral Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19 in Positive Interim Analysis of Phase 3 Study – READ – Based on 762 patients, 385 in the treatment group.
September 1, 2021 – Merck PRESS RELEASE: Merck and Ridgeback Biotherapeutics Announce Initiation of Pivotal Phase 3 MOVe-AHEAD Study Evaluating Molnupiravir for Post-Exposure Prophylaxis of COVID-19 Infection – Study Now Enrolling Participants Who Live in the Same Household as Someone With Symptomatic, Laboratory-Confirmed COVID-19 – READ
August 11, 2021 – Nature Structural & Molecular Biology: Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis – By Kabinger et al – READ
- “Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans.”
August 1, 2021 – The Journal of Infectious Diseases: β-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells by Zhou, Ralph Baric et al – READ, READ
July 12, 2021 – Merck PRESS RELEASE: Interim Results from Phase 2/3 Studies of Molnupiravir, an Investigational Oral Antiviral Therapeutic for Mild to Moderate COVID-19, Presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) – READ
June 9, 2021 – Merck PRESS RELEASE: Merck Announces Supply Agreement with U.S. Government for Molnupiravir, an Investigational Oral Antiviral Candidate for Treatment of Mild to Moderate COVID-19 – READ
April 15, 2021 – Merck PRESS RELEASE: Merck and Ridgeback Biotherapeutics Provide Update on Progress of Clinical Development Program for Molnupiravir, an Investigational Oral Therapeutic for the Treatment of Mild-to-Moderate COVID-19 – READ
March 6, 2021 – Merck PRESS RELEASE: Ridgeback Biotherapeutics and Merck Announce Preliminary Findings from a Phase 2a Trial of Investigational COVID-19 Therapeutic Molnupiravir – READ
January 25, 2021 – Merck PRESS RELEASE”: Merck Discontinues Development of SARS-CoV-2/COVID-19 Vaccine Candidates; Continues Development of Two Investigational Therapeutic Candidates – READ
2020
November 23, 2020 – Merck PRESS RELEASE: Merck to Acquire OncoImmune – READ
- OncoImmune’s lead product is CD24Fc, a first-in-class recombinant fusion protein that targets the innate immune system – Clinical Trial – READ, Study history – READ
October 5, 2020 – Clinical Trails: Efficacy and Safety of Molnupiravir (MK-4482) in Hospitalized Adult Participants With COVID-19 (MK-4482-001) – Sponsor MSD – READ – “Terminated (Business reasons)”, last updated on August 16, 2022!
- “For Business Reasons” is not a scientific or medical reason to terminate the study.” – SUBSTACK
October 5, 2020 – Clinical Trails: Efficacy and Safety of Molnupiravir (MK-4482) in Non-Hospitalized Adult Participants With COVID-19 (MK-4482-002) – READ
