Molnupiravir (MK-4482, EIDD-2801) Antiviral Description
Molnupiravir (MK-4482/EIDD-2801) is an experimental oral antiviral drug originally developed to treat influenza. It is an orally active prodrug of the synthetic nucleoside derivative N4-hydroxycytidine and exerts its antiviral action by introducing copying errors during viral RNA replication.
MK-4482/EIDD-2801 consists of the nucleoside analogue N4-hydroxycytidine (NHC). Molnupiravir has been evaluated against coronaviruses (CoVs), including SARS-1, MERS-CoV, and SARS-CoV-2.
Molnupiravir [USAN] RN: 2349386-89-4. UNII: YA84KI1VEW, InChIKey: HTNPEHXGEKVIHG-QCNRFFRDSA-N; PubChem CID145996610
Molnupiravir (MK-4482, EIDD-2801) Antiviral History
Molnupiravir was originally developed at Emory University by its drug innovation company, Drug Innovation Ventures at Emory (DRIVE). It was later acquired by Ridgeback Biotherapeutics, which has 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 anti-viral 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 severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection within 144 hours of polymerase chain reaction confirmation and are 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 7 days of onset of symptoms.
On July 1, 2020, Merck and Ridgeback Biotherapeutics LP announced 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.
A study published by the journal Nature on December 3, 2020, identified oral MK-4482/EIDD-2801 as a promising antiviral countermeasure to break SARS-CoV-2 community transmission chains.
On January 25, 2021, Merck stated Molnupiravir is currently being evaluated in Phase 2/3 clinical trials in both the hospital and out-patient 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.
Ridgeback Biopharmaceuticals was co-founded by CEO Wendy Holman and Dr. Wayne Holman, a scientific advisor to the company, focusing on developing anti-viral medications for diseases with epidemic and pandemic risk.
Molnupiravir (MK-4482, EIDD-2801) Antiviral Indication
Molnupiravir (MK-4482/EIDD-2801) antiviral is indicated to mitigate SARS-CoV-2 infection and block transmission, preventing COVID-19 disease.
Molnupiravir (MK-4482, EIDD-2801) Antiviral News
March 6, 2021 - Ridgeback Biotherapeutics and Merck Announce Preliminary Findings from a Phase 2a Trial of Investigational COVID-19 Therapeutic Molnupiravir. The findings reported on a secondary objective to reduce time to 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 LP. 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 pharmaceutical firm Merck.
December 5, 2020 - Researchers in the Institute for Biomedical Sciences at Georgia State University, led by Dr. Richard Plemper, found treating 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 analogue 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. This study identified oral MK-4482/EIDD-2801 as a promising antiviral countermeasure to break SARS-CoV-2 community transmission chains.'
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 anti-viral to be studied in the AGILE platform.
July 1, 2020 - Miami-based Ridgeback Biotherapeutics LP 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.
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.
Molnupiravir (MK-4482, EIDD-2801) Antiviral Clinical Trials
Clinical Trial NCT04746183: AGILE (Early Phase 1 Platform Trial for COVID-19)Last Update Posted on February 9, 2021. Estimated study completion: February 9, 2021
The AGILE platform master protocol allows incorporating a range of identified and yet-to-be-identified candidates as potential treatments for adults with COVID-19 into the trial. 200 Candidates will be added to the trial via candidate-specific trial (CST) protocols of this master protocol as appendices. Having one master protocol ensures different candidates are evaluated consistently, and opening up new trials for new candidates is more efficient. The inclusion of new candidates will be determined by the AGILE Scientific Advisory Board based on pre-clinical data, evidence in the clinical setting, and GMP capabilities.
Clinical Trial NCT04405739: The Safety of Molnupiravir (EIDD-2801) and Its Effect on Viral Shedding of SARS-CoV-2 (END-COVID) - Last Update Posted: February 21, 2021.
Phase 2a randomized, placebo-controlled, double-blinded clinical trial of EIDD-2801 in adult men and women who have tested positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection within 48 hours of polymerase chain reaction (PCR) confirmation and are 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 7 days of onset of symptoms. Stratified randomization of participants will receive remdesivir at enrollment and those who will not receive remdesivir at enrollment.
Clinical Trial NCT04405570: A Safety, Tolerability, and Efficacy of Molnupiravir (EIDD-2801) to Eliminate Infectious Virus Detection Persons With COVID-19. Last Update Posted: February 23, 2021.
This is a phase IIa, double-blind, placebo-controlled, randomized trial designed to compare the safety, tolerability, and antiviral activity of EIDD-2801 versus placebo as measured by infectious virus detection symptomatic adult outpatients with COVID-19. The study is a multicenter trial conducted in the United States. In this study, up to approximately 108 participants will be randomized to receive EIDD-2801 or Placebo orally twice a day (BID) for 5 days. The study may enroll up to 5 parts with subsequent doses that may be higher or lower than doses studied in previous cohorts and will be doses that have been studied for safety in a Phase 1 study. Doses will be chosen based on emerging virology and safety data from this and ongoing studies.
Clinical Trial NCT04575584: Efficacy and Safety of Molnupiravir (MK-4482) in Hospitalized Adult Participants With COVID-19 (MK-4482-001). Last Update Posted: March 5, 2021.
This study evaluates the safety, tolerability, and efficacy of molnupiravir (MK-4482) compared to placebo. The primary hypothesis is that molnupiravir is superior to placebo as assessed by the rate of sustained recovery through Day 29.
Clinical Trial NCT04575597: Efficacy and Safety of Molnupiravir (MK-4482) in Non-Hospitalized Adult Participants With COVID-19 (MK-4482-002). Last Update Posted: February 25, 2021.
This study evaluates the safety, tolerability, and efficacy of molnupiravir (MK-4482) compared to placebo. The primary hypothesis is that molnupiravir is superior to placebo as assessed by the percentage of hospitalized and/or dead participants through Day 29.