KENILWORTH, N.J. & MIAMI - Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Ridgeback Biotherapeutics announced that the U.S. Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for molnupiravir, an investigational oral antiviral (MK-4482, EIDD-2801). Molnupiravir has not been approved, but has been authorized for emergency use by the FDA under an EUA to treat mild to moderate coronavirus disease 2019 (COVID-19) in adults with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate. Molnupiravir 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, for use for longer than five consecutive days, or for pre-exposure or post-exposure prophylaxis for prevention of COVID-19.

'The FDA Emergency Use Authorization of molnupiravir is an important milestone in the fight against COVID-19, and adds to Merck's legacy of bringing forward innovative medicines that both address the world's greatest health threats and help save lives. Because we recognized the promise of molnupiravir early, Merck invested at risk and we are executing an unprecedented global access strategy so that molnupiravir, now authorized, can be available to patients here in the U.S. and all around the world more quickly and more equitably than has ever been accomplished before,' said Robert M. Davis, chief executive officer and president, Merck.

Molnupiravir should be administered as soon as possible after a diagnosis of COVID-19 has been made, and within five days of symptom onset. The recommended dose for molnupiravir is 800 mg (four 200 mg capsules) taken orally every 12 hours for five days, with or without food. Completion of the full five-day treatment course is important to maximize viral clearance and minimize transmission of SARS-CoV-2.

Molnupiravir is not recommended for use in patients who are pregnant. Based on findings from animal reproduction studies, molnupiravir may cause fetal harm when administered to pregnant individuals. There are no available human data on the use of molnupiravir in pregnant individuals to evaluate the risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Before initiating treatment with molnupiravir, it should be assessed whether an individual of childbearing potential is pregnant or not, if clinically indicated. Females of childbearing potential should use a reliable method of contraception correctly and consistently, as applicable, for the duration of treatment and for four days after the last dose of molnupiravir. Males of reproductive potential who are sexually active with females of childbearing potential should use a reliable method of contraception correctly and consistently during treatment and for at least three months after the last dose. There is a pregnancy surveillance program that monitors pregnancy outcomes in individuals exposed to molnupiravir during pregnancy. Patients exposed to molnupiravir during pregnancy should report the exposure by contacting Merck by phone at 1-877-888-4231, or online at pregnancyreporting.msd.com. For more information, see 'Selected Safety Information' below.

The authorization is based on the Phase 3 MOVe-OUT trial, which evaluated molnupiravir 800 mg twice-daily in non-hospitalized adult patients who were unvaccinated against SARS-CoV-2, had laboratory-confirmed SARS-CoV-2 infection, symptom onset within five days of study randomization, and at least one risk factor associated with poor disease outcomes (e.g., heart disease, diabetes).

In analyses from all randomized patients (n=1433), molnupiravir reduced the risk of hospitalization or death: 9.7% (68/699) of patients in the placebo group were hospitalized or died compared to 6.8% (48/709) of patients who received molnupiravir, for an absolute risk reduction of 3.0% (95% confidence interval [CI]: 0.1, 5.9). Nine deaths were reported in the placebo group, and one in the molnupiravir group.

The determination of primary efficacy was based on a planned interim analysis of 762 subjects. At the interim analysis, treatment with molnupiravir significantly reduced hospitalizations and death through Day 29 following randomization: 14.1% (53/377) of patients in the placebo group were hospitalized or died, compared to 7.3% (28/385) of patients who received molnupiravir. The absolute risk reduction between the molnupiravir and the placebo arm was 6.8 percentage points (95% CI: 2.4, 11.3; p=0.0024).

In the clinical study, the most common adverse reactions for molnupiravir (incidence ?1%) were diarrhea (2% for molnupiravir, 2% for placebo), nausea (1% for molnupiravir, 1% for placebo) and dizziness (1% for molnupiravir, 1% for placebo). Discontinuation of study intervention due to an adverse event (AE) occurred in 1% of subjects receiving molnupiravir and 3% of subjects receiving placebo. Serious AEs occurred in 7% of subjects receiving molnupiravir and 10% receiving placebo; most serious AEs were COVID-19 related.

'Based on the strong science behind molnupiravir - a single oral medicine that interrupts replication of the SARS-CoV-2 virus, with data demonstrating a significant reduction in the risk of hospitalizations and deaths - molnupiravir has the potential to become an important tool for healthcare professionals and appropriate patients,' said Dr. Dean Y. Li, president, Merck Research Laboratories. 'We are immensely grateful to all of our collaborators, including trial patients and clinical investigators, for their important contributions to this milestone.'

Merck anticipates that it will begin shipping molnupiravir to AmerisourceBergen, the sole distributor of molnupiravir, within days. As previously announced, Merck entered into a procurement agreement with the U.S. Government under which, to date, the company has agreed to supply approximately 3.1 million courses of molnupiravir to the U.S. Government, upon EUA from the FDA.

'Before the virus that caused this tragic pandemic had a name, the team at Ridgeback saw the need for urgent action. We joined with George Painter, Drug Research Innovations at Emory (DRIVE) and Merck with the hope of taking molnupiravir from a dream to the reality we see today,' said Wendy Holman, chief executive officer, Ridgeback Biotherapeutics. 'There is now a prescription oral antiviral, molnupiravir, for use by appropriate high-risk patients, that can be taken at home, as soon as possible after an appropriate patient tests positive for COVID-19, to help reduce the risk of hospitalization or death. It's an oral therapeutic option with no known drug-drug interactions and without required dose modifications for those with impaired kidney or liver function. We are thrilled this tremendous global collaboration between Ridgeback, Merck and DRIVE has fulfilled our hopes of bringing forward an oral medicine to help keep people out of the hospital and alive.'

Molnupiravir is also being evaluated for post-exposure prophylaxis in MOVe-AHEAD, a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study, which is evaluating the efficacy and safety of molnupiravir in preventing the spread of COVID-19 within households. Molnupiravir is not authorized for pre-exposure or post-exposure prophylaxis for prevention of COVID-19.

An EUA is an FDA authorization for the emergency use of an unapproved product or unapproved use of an approved product in the U.S. under certain circumstances, including a public health emergency. Molnupiravir is an investigational treatment and is still under review by the FDA.

Recently, the FDA Antimicrobial Drugs Advisory Committee (AMDAC) voted that the known and potential benefits of molnupiravir outweigh its known and potential risks for the treatment of mild to moderate COVID-19 in high risk adult patients who are within five days of symptom onset. Molnupiravir has received conditional marketing authorization in the United Kingdom for the treatment of mild to moderate COVID-19 in adults with a positive SARS-CoV-2 diagnostic test and who have at least one risk factor for developing severe illness. The European Medicines Agency (EMA) issued a positive scientific opinion for molnupiravir under Article 5.3 Regulation 726/2004, which is intended to support national decision-making on the possible use of molnupiravir prior to marketing authorization. Applications to other regulatory bodies worldwide are underway.

About Merck's Global Efforts to Accelerate Access to Molnupiravir Following Regulatory Authorizations or Approvals

Global access has been a priority for Merck and Ridgeback since the inception of their molnupiravir collaboration. The companies are committed to providing timely access to molnupiravir globally through our comprehensive supply and access approach, which includes 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.

Supply: In anticipation of the results from MOVe-OUT and the potential for regulatory authorization or approval, Merck has been producing molnupiravir at risk and expects to produce 10 million courses of treatment by the end of 2021, with at least 20 million courses to be produced in 2022.

Supply agreements: Merck entered into a procurement agreement with the U.S. Government under which the company will supply approximately 3.1 million courses of molnupiravir to the U.S. Government, upon Emergency Use Authorization or approval from the U.S. Food and Drug Administration. Merck has entered into advance purchase and supply agreements for molnupiravir with the governments of over 30 countries worldwide, including Australia, Canada, Korea, Japan, Thailand, United Kingdom and United States, pending regulatory authorizations, and is currently in discussions with additional governments. Merck plans to implement a tiered pricing approach based on World Bank country income criteria to reflect countries' relative ability to finance their health response to the pandemic. In the United States, the purchase was funded with federal funds from the Biomedical Advanced Research and Development Authority, part of the U.S. Department of Health and Human Services' Office of the Assistant Secretary for Preparedness and Response, under contract number W911QY-21-C-0031.

Voluntary licenses: As part of its commitment to widespread global access, Merck previously announced that it has entered into a licensing agreement with the Medicines Patent Pool to increase broad access for molnupiravir in low- and middle-income countries. Additionally, Merck previously announced that the company has entered into non-exclusive voluntary licensing agreements for molnupiravir with established generic manufacturers to accelerate availability of molnupiravir in more than 100 low- and middle-income countries following approvals or emergency authorization by local regulatory agencies.

Merck continues to discuss additional measures and collaborations to accelerate broad, global access to molnupiravir.

Authorized Use of Molnupiravir

The U.S. Food and Drug Administration (FDA) has issued an EUA for the emergency use of the unapproved molnupiravir, a nucleoside analogue that inhibits SARS-CoV-2 replication by viral mutagenesis, for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adults with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by FDA are not accessible or clinically appropriate.Molnupiravir is not FDA-approved for any use including for use for the treatment of COVID-19. Prior to initiating treatment with molnupiravir, carefully consider the known and potential risks and benefits.

Molnupiravir is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of molnupiravir under section 564(b)(1) of the Federal, Food, Drug, and Cosmetic Act, 21 U.S.C. (*) 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

Molnupiravir is not authorized for use in patients less than 18 years of age or who are hospitalized due to COVID-19. Benefit of treatment with molnupiravir has not been observed in subjects when treatment was initiated after hospitalization due to COVID-19. Molnupiravir is not authorized for use for longer than five consecutive days. Molnupiravir is not authorized for pre-exposure or post-exposure prophylaxis for prevention of COVID-19. Molnupiravir 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 molnupiravir belongs (i.e., anti-infectives).

Selected Safety Information for Molnupiravir

Contraindications

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

Warnings and Precautions

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

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

Molnupiravir 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 molnupiravir during pregnancy, the prescribing healthcare provider must document that the that the known and potential benefits and the potential risks of using molnupiravir during pregnancy were communicated to the pregnant individual.

There is a pregnancy surveillance program that monitors pregnancy outcomes in individuals exposed to molnupiravir during pregnancy. The prescribing healthcare provider must document that a pregnant individual was made aware of Merck's pregnancy surveillance program at 1-877-888-4231 or pregnancyreporting.msd.com. If the pregnant individual agrees to participate in the pregnancy surveillance program and allows the prescribing healthcare provider to disclose patient specific information to Merck, the prescribing healthcare provider must provide the patient's name and contact information to Merck. Pregnant individuals exposed to molnupiravir can also report the exposure by contacting Merck at 1-877-888-4231 or pregnancyreporting.msd.com.

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 molnupiravir and for 4 days after the final dose.

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

Molnupiravir 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 molnupiravir have not been established in pediatric patients.

Adverse Reactions

The most common adverse reactions occurring in ?1% of subjects in the molnupiravir 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 molnupiravir and 10% receiving placebo; most serious adverse events were COVID-19 related. Adverse events leading to death occurred in 2 (

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