Merck and Ridgeback Biotherapeutics Announce Initiation of Phase 3 Study (MOVe-NOW) Evaluating LAGEVRIO™ (molnupiravir) for the Treatment of COVID-19 in High-Risk Adults

MOVe-NOW will build on existing LAGEVRIO data to assess efficacy in the current COVID-19 environment and support applications for licensure

Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the initiation of the Phase 3 MOVe-NOW clinical trial to evaluate LAGEVRIO^TM (molnupiravir), an investigational oral antiviral COVID-19 medicine, for the treatment of adults with COVID-19 at high risk for disease progression. This double-blind, placebo-controlled, global study is enrolling individuals who are at least 18 years of age, tested positive for SARS-CoV-2 infection, have had COVID-19 symptoms for four days or less, and are not hospitalized. Additionally, the study will only enroll adults who cannot receive nirmatrelvir/ritonavir (NMV/r) due to drug-drug interactions, allergy, previous adverse effects, or inaccessibility.

The MOVe-NOW study will use a different formulation of LAGEVRIO that includes two smaller 400-mg tablets per dose (four daily tablets) instead of the currently available four 200-mg capsules per dose (eight daily capsules). The smaller tablets are not currently approved for use in any country. For more information on the trial, visit clinicaltrials.gov.

“COVID-19 remains a leading cause of hospitalization and death around the world, and further studying LAGEVRIO may provide important insights into how it may be used to help prevent severe outcomes in the current COVID-19 environment,” said Dr. Paula Annunziato, senior vice president, infectious diseases and vaccines, Global Clinical Development, Merck Research Laboratories. “We continue to believe LAGEVRIO may be an important option for people with risk factors like older age, multiple comorbidities, and immunocompromising conditions, who are more likely to advance to severe COVID-19, and for whom other antiviral treatments may not be appropriate because of the potential for drug-drug interactions.”

LAGEVRIO is approved or authorized for use in several countries, including Japan, Australia, and available for use in the United States under emergency use authorization, for the treatment of certain adults who have been diagnosed with COVID-19. To date, LAGEVRIO has been used by more than 8.3 million patients worldwide.

About the MOVe-NOW Study

MOVe-NOW (MK-4482-023, NCT06667700) is a Phase 3 multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of orally administered LAGEVRIO compared with placebo in non-hospitalized adults with COVID-19 at high risk for disease progression. The trial is anticipated to enroll approximately 3,082 participants who will be randomized to receive either LAGEVRIO (800 mg) or placebo orally every 12 hours for five days. The study will enroll participants who are at least 18 years of age and have received a positive test for SARS-CoV-2 infection with signs or symptoms attributable to COVID-19 for four days or less and will only enroll adults who cannot receive nirmatrelvir/ritonavir (NMV/r) due to drug-drug interactions, allergy, previous adverse effects, or inaccessibility. The trial is being conducted in 25 markets around the world, including the United States, Japan, Korea, Taiwan, the United Kingdom, France, Italy, Spain, Ukraine, Poland, Mexico, and Colombia, among others.

Investigators may decide to treat some study participants with concomitant remdesivir, if available and clinically appropriate per local clinical practice, as local standard of care in addition to LAGEVRIO or placebo. Study investigators should aim to ensure that those who are most vulnerable to severe COVID-19 receive timely access to remdesivir as standard of care.

The primary efficacy and safety endpoints of the trial include the percentage of participants who were hospitalized or died for any reason or had a COVID-19-related medically-attended visit through Day 29; the percentage of participants with an adverse event; and the percentage of participants who discontinued LAGEVRIO due to an adverse event.

A key secondary endpoint is sustained alleviation without relapse of selected participant-reported COVID-19 signs and symptoms through Day 29. Additional secondary endpoints through Day 29 include evaluation of SARS-CoV-2 viral load, time to sustained resolution without relapse of COVID-19 signs and symptoms, and percentage of participants with clinically important medical interventions associated with a COVID-19-related medically attended visit or hospitalization, or who experienced hospitalization or death due to any cause. The study includes an extended follow up of approximately five and a half months after treatment ends to evaluate endpoints associated with post-acute sequelae of COVID-19 (PASC, or long COVID). Development of PASC will be assessed on Day 29 and during the extended follow-up period (i.e., Day 56, Day 112, and Day 168) based on self-reported COVID-19 signs/symptoms.

Authorized Use of LAGEVRIO^TM (molnupiravir) in the U.S.

LAGEVRIO (molnupiravir) is authorized for use under an Emergency Use Authorization (EUA) for the treatment of adults with mild-to-moderate coronavirus disease 2019 (COVID-19):

• who are at high risk for progression to severe COVID-19, including hospitalization or death, and
• for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate.

LAGEVRIO is not approved for any use, including the treatment of COVID-19, but is authorized for emergency use by the FDA under an Emergency Use Authorization (EUA).

The emergency use of LAGEVRIO is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the COVID-19 pandemic under Section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1) unless the declaration is terminated or authorization revoked sooner.

Limitations of Authorized Use

LAGEVRIO is not authorized:

• for use in patients who are less than 18 years of age
• for initiation of treatment in patients hospitalized due to COVID-19. Benefit of treatment with LAGEVRIO has not been observed in subjects when treatment was initiated after hospitalization due to COVID-19
• for use for longer than 5 consecutive days
• for pre-exposure or post-exposure prophylaxis for prevention of COVID-19

LAGEVRIO may only be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs in the therapeutic class to which LAGEVRIO belongs (ie, anti-infectives).

Selected Safety Information for LAGEVRIO

Contraindications

No contraindications have been identified based on the limited available data on the emergency use of LAGEVRIO authorized under this EUA.

Warnings and Precautions

There are limited clinical data available for LAGEVRIO. Serious and unexpected adverse events may occur that have not been previously reported with LAGEVRIO use.

LAGEVRIO is not recommended for use during pregnancy. Based on findings from animal reproduction studies, LAGEVRIO may cause fetal harm when administered to pregnant individuals. There are no available human data on the use of LAGEVRIO in pregnant individuals to evaluate the risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

LAGEVRIO is authorized to be prescribed to a pregnant individual only after the healthcare provider has determined that the benefits would outweigh the risks for that individual patient. If the decision is made to use LAGEVRIO during pregnancy, the prescribing healthcare provider must document that the known and potential benefits and the potential risks of using LAGEVRIO during pregnancy were communicated to the pregnant individual.

There is a pregnancy registry that monitors pregnancy outcomes in individuals exposed to LAGEVRIO during pregnancy. The prescribing healthcare provider must document that a pregnant individual was made aware of the pregnancy registry at https://covid-pr.pregistry.com or 1-800-616-3791. Pregnant individuals exposed to LAGEVRIO or their healthcare providers can also report the exposure by contacting Merck Sharp & Dohme LLC, Rahway, NJ USA at 1-877-888-4231.

Advise individuals of childbearing potential of the potential risk to a fetus and to use an effective method of contraception correctly and consistently during treatment with LAGEVRIO and for 4 days after the final dose.

Prior to initiating treatment with LAGEVRIO, assess whether an individual of childbearing potential is pregnant or not, if clinically indicated.

Hypersensitivity reactions, including anaphylaxis, have been reported with LAGEVRIO. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue LAGEVRIO and initiate appropriate medications and/or supportive care.

LAGEVRIO is not authorized for use in patients less than 18 years of age because it may affect bone and cartilage growth. The safety and efficacy of LAGEVRIO have not been established in pediatric patients.

Adverse Reactions

The most common adverse reactions occurring in ≥1% of subjects in the LAGEVRIO treatment group in the Phase 3 double-blind MOVe-OUT study were diarrhea (2% versus placebo at 2%), nausea (1% versus placebo at 1%), and dizziness (1% versus placebo at 1%) all of which were Grade 1 (mild) or Grade 2 (moderate).

Serious adverse events occurred in 7% of subjects receiving LAGEVRIO and 10% receiving placebo; most serious adverse events were COVID-19 related. Adverse events leading to death occurred in 2 (<1%) of the subjects receiving LAGEVRIO and 12 (2%) of subjects receiving placebo.

Drug Interactions

No drug interactions have been identified based on the limited available data on the emergency use of LAGEVRIO. No clinical drug-drug interaction trials of LAGEVRIO with concomitant medications, including other treatments for mild-to-moderate COVID-19, have been conducted.

Pregnancy/Breastfeeding

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 LAGEVRIO, breastfeeding is not recommended during treatment with LAGEVRIO and for 4 days after the final dose. A lactating individual may consider interrupting breastfeeding and may consider pumping and discarding breast milk during treatment and for 4 days after the last dose of LAGEVRIO.

Males of Reproductive Potential

While the risk is regarded as low, there is a theoretical risk for LAGEVRIO to affect offspring of treated males based on its mechanism of action. Advise sexually active individuals with partners of childbearing potential to use a reliable method of contraception correctly and consistently during treatment and for at least 3 months after the last dose of LAGEVRIO. The risk beyond three months after the last dose of LAGEVRIO is unknown.

Required Reporting for Serious Adverse Events and Medication Errors

The prescribing healthcare provider and/or the provider’s designee is/are responsible for mandatory reporting of all serious adverse events and medication errors potentially related to LAGEVRIO within 7 calendar days from the healthcare provider’s awareness of the event.

Submit adverse event and medication error reports, using FDA Form 3500, to FDA MedWatch using one of the following methods:

• Complete and submit the report online: www.fda.gov/medwatch/report.htm
• Complete and submit a postage-paid FDA Form 3500 (https://www.fda.gov/media/76299/download) and return by:
  • Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or
  • Fax to 1-800-FDA-0178 or
• Call 1-800-FDA-1088 to request a reporting form
  
  
  
  In addition, please provide a copy of all FDA MedWatch forms to:
  
  Merck Sharp & Dohme LLC, Rahway, NJ USA by:
• Fax: 215-616-5677
• E-mail: dpoc.usa@merck.com

About LAGEVRIO (molnupiravir)

LAGEVRIO (molnupiravir) (MK-4482) is an investigational, orally administered nucleoside analog that inhibits the replication of SARS-CoV-2, the causative agent of COVID‑19.

Merck and Ridgeback’s “orange COVID-19 pill” is a Swedish Orange opaque capsule with the Merck corporate logo and “82” printed in white ink, available in certain markets as LAGEVRIO.

Molnupiravir was invented at Emory University. Drug Innovation Ventures at Emory (DRIVE), LLC, which was formed by Emory to develop early-stage drug candidates for viral diseases of global concern, advanced molnupiravir through IND submission. Emory/DRIVE received some research funding from the U.S. Department of Defense and the U.S. National Institutes of Health. LAGEVRIO is being developed by Merck in collaboration with Ridgeback Biotherapeutics. Ridgeback received an upfront payment from Merck and also is eligible to receive contingent payments dependent upon the achievement of certain developmental and regulatory approval milestones. Profits from the collaboration are split between the partners equally. Since licensed by Ridgeback, all funds used for the development of LAGEVRIO have been provided by Merck and Ridgeback.

About Ridgeback Biotherapeutics

Headquartered in Miami, Florida, Ridgeback Biotherapeutics LP is a biotechnology company focused on emerging infectious diseases. Ridgeback developed Ebanga^TM for the treatment of Ebola and has a late-stage development pipeline which includes molnupiravir for the treatment of COVID-19. The team at Ridgeback is dedicated to developing life-saving and life-changing solutions for patients and diseases that need champions as well as providing global access to these medicines. In line with Ridgeback’s mission for equitable global access, all Ridgeback services and treatment for Ebola patients in Africa are delivered free of charge. For more information, visit www.ridgebackbio.com.

About Merck

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., US

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2023, and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Before prescribing LAGEVRIO™ (molnupiravir), please read the Fact Sheet for Healthcare Providers, including Mandatory Requirements for Administration of LAGEVRIO under Emergency Use Authorization, at https://www.merck.com/eua/molnupiravir-hcp-fact-sheet.pdf and Fact Sheet for Patients and Caregivers at https://www.merck.com/eua/molnupiravir-patient-fact-sheet-english.pdf

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