RAHWAY, N.J. & MIAMI--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Ridgeback Biotherapeutics today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the refusal of the marketing authorization for LAGEVRIO™ (molnupiravir) for the treatment of certain adults who have been diagnosed with COVID-19 in the European Union (EU). Merck and Ridgeback will appeal the decision and request a re-examination of the CHMP’s opinion.

“We believe the CHMP’s recommendation does not reflect the compelling data generated from the Phase 3 MOVe-OUT trial and from real-world studies demonstrating the positive impact that LAGEVRIO can provide for patients by reducing the risk of hospitalization and death among adults at increased risk for severe disease,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “More than 4 million patients worldwide have been treated with LAGEVRIO. We remain confident that LAGEVRIO has an important role to play in the COVID‑19 treatment landscape and will appeal this opinion.”

“LAGEVRIO is prescribed globally as an important medicine for appropriate adult patients at risk for severe disease, and there is a critical need for multiple approaches to treat COVID-19,” said Wendy Holman, chief executive officer, Ridgeback Biotherapeutics.

The EMA scientific opinion under Article 5(3) of Regulation (EC) 726/2004, which has supported the decision by 16 EU national authorities to make LAGEVRIO available, remains in effect.

LAGEVRIO is approved or authorized for use in more than 25 countries, including Australia, Japan, the United States, the United Kingdom, and China for the treatment of certain adults who have been diagnosed with COVID-19. LAGEVRIO has been used in more than 4 million patients worldwide, and recent real-world studies – conducted across different geographies during the Omicron variant surge and as availability of effective vaccines has increased – support the clinical profile of LAGEVRIO as a treatment option for certain adults with mild to moderate COVID-19 who are at high risk for severe disease.

About Merck’s Global Efforts to Accelerate Access to LAGEVRIO (molnupiravir) Following Regulatory Authorizations or Approvals

Global access has been a priority for Merck and Ridgeback since the inception of their collaboration. The companies are committed to providing timely access to LAGEVRIO globally through our comprehensive supply and access approach, which included investing at risk to produce millions of courses of therapy; tiered pricing based on the ability of governments to finance health care; entering into supply agreements with governments; and granting voluntary licenses to generic manufacturers and to the Medicines Patent Pool to make generic molnupiravir available in more than 100 low- and middle-income countries following local regulatory authorizations or approvals. To supplement the supply from licensed generic manufacturers and bridge to the availability of WHO prequalified generic supply, Merck entered into agreements with UNICEF and USAID to allocate up to a total of 5 million courses of LAGEVRIO to low- and middle-income countries.

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

The U.S. Food and Drug Administration (FDA) has issued an EUA for the emergency use of the unapproved product LAGEVRIO, a nucleoside analogue that inhibits SARS-CoV-2 replication by viral mutagenesis, for the treatment of adults with a current diagnosis of 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 FDA-approved for any use, including the treatment of COVID-19.

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.

LAGEVRIO is not authorized for use in patients less than 18 years of age or 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. LAGEVRIO is not authorized for use for longer than five consecutive days. LAGEVRIO is not authorized 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 (i.e., 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 (