Merck Provides Update on Phase 3 MOVe-AHEAD Trial Evaluating LAGEVRIO™ (molnupiravir) for Post-exposure Prophylaxis for Prevention of COVID-19
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that LAGEVRIO™ (molnupiravir) did not demonstrate a statistically significant reduction in the risk of COVID-19 following household exposure to another individual with COVID-19. The Phase 3 MOVe-AHEAD trial evaluated people who did not have COVID-19 at baseline (confirmed by a negative baseline SARS-CoV-2 test and no signs and symptoms) but lived with someone who was recently diagnosed with COVID-19. In the primary endpoint of participants who did not have evidence of SARS-CoV-2 infection at baseline (confirmed by a negative SARS-CoV-2 test), the LAGEVRIO treated group was observed to be 23.6% less likely than those who received placebo to develop COVID-19 through Day 14 (a positive post-baseline SARS-CoV-2 test with evidence of signs and symptoms); the primary endpoint was not met. The safety profile of LAGEVRIO in this trial was generally consistent with that observed in previously reported clinical studies and post-authorization experience in the treatment of COVID-19. Merck intends to submit full results from this study for presentation at a scientific meeting or for publication.
“Results from this post-exposure prevention study are scientifically interesting as we continue to learn more about COVID-19. We are grateful to the MOVe-AHEAD trial participants and investigators for their contributions to this study,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “This was not a treatment study and these results do not impact the efficacy and safety data observed in our Phase 3 MOVe-OUT trial for the treatment of mild-to-moderate COVID-19. We remain focused on our ongoing efforts to bring LAGEVRIO as treatment to appropriate high-risk patients with COVID-19 where its use is authorized or approved, as well as to further study the ways it may benefit patients with other infectious diseases, such as RSV.”
LAGEVRIO is approved or authorized in several markets including the U.S., United Kingdom, Australia, China and Japan, for the treatment of certain adults who have been diagnosed with COVID-19. See additional information on the authorized use of LAGEVRIO in the U.S. below. LAGEVRIO is not authorized for pre-exposure or post-exposure prophylaxis for prevention of COVID-19.
About the MOVe-AHEAD Study
MOVe-AHEAD (MK-4482-013) (NCT04939428) was a Phase 3 multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of orally administered LAGEVRIO (molnupiravir) compared to placebo in preventing the spread of SARS-CoV-2, the virus that causes COVID-19, within households. The trial enrolled over 1,500 participants who were randomized to receive either LAGEVRIO (800 mg) or placebo orally every 12 hours for five days. The study enrolled participants who were at least 18 years of age and resided in the same household with someone who received a positive test for SARS-CoV-2, had at least one sign or symptom of COVID-19 and had not had those signs and symptoms for more than five days. Participants were not eligible for the trial if they received the first dose of a COVID-19 vaccine more than seven days prior to enrollment, previously had COVID-19 within the past six months or were showing any signs or symptoms of COVID-19.
The primary endpoints of the trial included percentage of participants who have undetectable SARS-CoV-2 in baseline nasopharyngeal (NP) swabs and develop COVID-19 through Day 14, percentage of participants with an adverse event and percentage of participants who discontinued study intervention due to an adverse event.
The trial was conducted globally in countries including Argentina, Brazil, Bulgaria, Colombia, Egypt, France, Guatemala, Hungary, Japan, Kenya, Mexico, Philippines, Romania, Russia, South Africa, Thailand, Turkey, Ukraine, and the United States.
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 Biotherapeutics LP, a biotechnology company focused on emerging infectious diseases, since the inception of their LAGEVRIO collaboration. The companies are committed to providing timely access to LAGEVRIO globally through our comprehensive supply and access approach, which includes:
Supply: Patients around the world have received approximately 4 million courses of LAGEVRIO. Merck has supplied LAGEVRIO to more than 40 markets worldwide.
Voluntary licenses: As part of its commitment to widespread global access, Merck granted voluntary licenses (VLs) to generic manufacturers and to the Medicines Patent Pool to make generic molnupiravir available in more than 100 low- and middle-income countries following approvals or emergency authorization by local regulatory agencies. Through our voluntary licensing agreements with generic manufacturers, more than 5 million courses of generic molnupiravir have been delivered to 22 markets through December 2022. Additionally, Hetero Labs, Ltd. has received WHO prequalification, an important step in enabling broader access to molnupiravir.
UNICEF: To supplement the supply from licensed generic manufacturers and bridge to the availability of WHO prequalified generic supply, Merck entered into an agreement with UNICEF to allocate up to 3 million courses of LAGEVRIO to facilitate timely supply to low- and middle-income countries. Merck has also committed 2 million patient courses of LAGEVRIO, available to USAID at Merck’s best access price to increase access in lower-income countries.
Product donation: Merck has donated 100,000 courses of therapy to Direct Relief, a global humanitarian aid organization, for distribution to refugees, including 50,000 courses of therapy for people affected by the invasion of Ukraine.
Purchase and supply agreements: Merck entered into a procurement agreement with the U.S. government under which the company supplied approximately 3.1 million courses of LAGEVRIO to the U.S. government, upon Emergency Use Authorization from the U.S. Food and Drug Administration. The U.S. Department of Health and Human Services (HHS) has created a Test-to-Treat locator to help identify pharmacies and community health centers across the nation where people can get tested for COVID-19 and receive appropriate treatments, as needed.
Merck has also entered into additional advance purchase and supply agreements for LAGEVRIO with governments of more than 40 markets worldwide and is currently in discussions with additional governments. Merck is implementing a tiered-pricing approach based on World Bank country income criteria to reflect countries’ relative ability to finance their health response to the pandemic.
Responding to global needs with urgency: In September 2022, Merck announced a cooperation framework agreement with Sinopharm Group Co. Ltd., under which Merck granted distribution and exclusive import rights for LAGEVRIO to Sinopharm following authorization. To date, we have shipped more than one million courses of LAGEVRIO to China, with additional shipments planned.
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 (
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