Molnupiravir

RAHWAY, N.J. & MIAMI--( BUSINESS WIRE )--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

RAHWAY, N.J.--( BUSINESS WIRE )--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced its plans to present new research findings demonstrating the continued impact of its increasingly broad and diverse vaccines and infectious disease portfolio and the potential of its innovative pipeline at IDWeek 2024 in Los Angeles, CA, from October 16-19. Data to be presented include a late-breaker oral presentation of positive detailed results from the Phase 2b/3 trial evaluating clesrovimab (MK-1654), an investigational prophylactic monoclonal antibody designed to protect infants from respiratory syncytial virus (RSV) disease; data from the Phase 3 STRIDE-8 trial evaluating CAPVAXIVE™ (Pneumococcal 21-valent Conjugate Vaccine) in adults 18-64 years of age at increased risk of pneumococcal disease; as well as a late-breaker oral presentation of Week 48 data from the Phase 2 study evaluating an investigational once-weekly oral combination regimen of islatravir, the company’s nucleoside reverse transcriptase translocation inhibitor (NRTTI), and Gilead’s lenacapavir, a first-in-class capsid inhibitor, for treatment of people with HIV-1 infection. “ The breadth of innovative research we will showcase during IDWeek 2024 is a testament to our ongoing commitment to advancing science with the pursuit of addressing persisting global health needs, such as RSV,” said Dr. Paula Annunziato, senior vice president, infectious diseases and vaccines, Global Clinical Development, Merck Research Laboratories. “ We are proud of our company’s longstanding legacy and continued momentum in helping to treat and prevent a variety of potentially serious infectious diseases for individuals around the world and across all stages of life – from birth through older adulthood – and we look forward to sharing these data.” Key data from Merck’s portfolio and pipeline to be presented during IDWeek 2024: First time data from the Phase 2b/3 study evaluating a single dose of clesrovimab (MK-1654) administered to pre-term and full-term infants (Abstract #166, Late Breaker Oral Abstract Session: Respiratory Viruses Across All Ages); First presentation of results from the interim analysis of the Phase 3 trial evaluating the safety and efficacy of clesrovimab versus palivizumab in infants and children at increased risk for severe RSV disease (Abstract #167, Late Breaker Oral Abstract Session: Respiratory Viruses Across All Ages); First presentation of data from the Phase 3 STRIDE-8 trial evaluating CAPVAXIVE in vaccine-naïve adults 18-64 years of age at increased risk of pneumococcal disease (Abstract #45, Poster Session: Adult Vaccines); Week 48 data from the Phase 2 study evaluating once-weekly oral islatravir plus lenacapavir (Abstract #577, Late Breaker Oral Abstract Session: What's Going Viral); Data from the SPECTRA (Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam [C/T] Real-world Analysis) study (multiple abstracts) and updates from the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance program (multiple abstracts). Details on abstracts listed above and additional key abstracts for Merck: RSV A Phase 2b/3 Study to Evaluate the Efficacy and Safety of an Investigational Respiratory Syncytial Virus (RSV) Antibody, Clesrovimab, in Healthy Preterm and Full-Term Infants. A. Sinha. Abstract #166, Oral Abstract, Late Breaker Abstract Session: Respiratory Viruses Across All Ages Phase 3, Randomized, Controlled Trial Evaluating Safety, Efficacy, and Pharmacokinetics (PK) of Clesrovimab in Infants and Children at Increased Risk for Severe Respiratory Syncytial Virus (RSV) Disease. O. Ramilo. Abstract #167, Oral Abstract, Late Breaker Abstract Session: Respiratory Viruses Across All Ages Pneumococcal A Phase 3, Randomized Trial Investigating the Safety, Tolerability, and Immunogenicity of V116, an Investigational Adult-Specific Pneumococcal Conjugate Vaccine, in Pneumococcal Vaccine-Naïve Adults 18–64 Years of Age with Increased Risk for Pneumococcal Disease. P. Scott. Abstract #45, Poster Session: Adult Vaccines Disparities and Inequities in the Burden of Pneumococcal Disease in US Adults. N. Cossrow. Abstract #242, Poster Session: HAIs: Device-Associated (CLABSI, CAUTI, VAP) Quantifying the Impact of Introducing a New Adult-Focused PCV in the United States. O. Sharomi. Abstract #58, Poster Session: Adult Vaccines HIV Week 48 Results of a Phase 2 Study Evaluating Once-weekly Oral Islatravir Plus Lenacapavir. A. Colson. Abstract #577, Oral Abstract, Late Breaker Abstract Session: What's Going Viral Undesired Weight Gain and Associated Healthcare Outcomes Among People with HIV on Antiretroviral Treatment. B.K. Tadese. Abstract #540, Poster Session: HIV: Treatment Antivirals Drug-Drug Interactions (DDIs) with Letermovir (LET) for Cytomegalovirus (CMV) Prophylaxis in Pediatric (Birth to <18 Years of Age) Hematopoietic Cell Transplant (HCT) Recipients. L. Danziger-Isakov. Abstract #1196, Poster Session: Pediatric Viral Studies A SFGM-TC Real-world Study to Characterize Pediatric Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) and Identify Both the Cytomegalovirus (CMV) Serology Status of Both Recipients and Their Donors. X. Bourge. Abstract #2356, Poster Session: Virology: Epidemiology of Viral Infections Virologic and Clinical Outcomes Among Participants Hospitalized in a Phase 3 Trial Comparing Molnupiravir with Placebo for Treating Mild-to-Moderate COVID-19. M. Johnson. Abstract #1928, Poster Session: COVID-19: Complications, Coinfections and Clinical Outcomes Antibiotics Treatment Patterns Among Hospitalized Patients with Gram-Negative Infection Treated with Imipenem/Cilastatin/Relebactam (I/R): Retrospective US-Based EHR Medical Chart Review. E. Yucel. Abstract #1075, Poster Session: Novel Agents Effectiveness of Imipenem-Relebactam for Multidrug-resistant Pseudomonas AeruGinosa in PnEumonia and Bloodstream Infections in the United States (MIRAGE): Preliminary Results. R. Shields. Abstract #1105, Poster Session: Novel Agents Comparative Effectiveness of Early Treatment with Ceftolozane/Tazobactam (C/T) Relative to Polymyxin (PB)-based Therapy for Non-COVID-19 Patients (pts) with Pneumonia (PNA) due to Multi-drug Resistant Pseudomonas Aeruginosa (MDR-PSA) Across US Hospitals. T. Lodise. Abstract #1537, Poster Session: Treatment of Antimicrobial Resistant Infections Clinical Outcomes in Patients Hospitalized with Exacerbation of Chronic Respiratory Infections Treated with Ceftolozane/Tazobactam: Results from SPECTRA. E. Yucel. Abstract #1074, Poster Session: Novel Agents Describing the Clinical Characteristics, Treatment Patterns and Outcomes in Hospitalized Pneumonia Patients Treated with Ceftolozane/Tazobactam (C/T): Insights from the SPECTRA Study. E. Yucel. Abstract #1076, Poster Session: Novel Agents Treatment Patterns and Clinical Outcomes in Hospitalized Patients with Febrile Neutropenia Treated with Ceftolozane/Tazobactam: A Subgroup Analysis of the SPECTRA Study. E. Yucel. Abstract #1113, Poster Session: Novel Agents Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam [C/T) Real-world Analysis Results (SPECTRA): Results of Immunocompromised Patients. E. Yucel. Abstract #2305, Poster Session: Transplant: Studies of Empiric and Preemptive Therapy Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam (C/T) Real-world Analysis (SPECTRA): Clinical Outcomes and Treatment Patterns from Mexico. E. Yucel. Abstract #1077, Poster Session: Novel Agents Antimicrobial Epidemiology/Surveillance Susceptibility of Clinical Non-Morganellaceae Enterobacterales Isolates from Bloodstream and Respiratory Tract Infections to Imipenem/Relebactam and Comparators: SMART United States 2020-2022. M. Wise. Abstract #1519, Poster Session: Treatment of Antimicrobial Resistant Infections Activity of Ceftolozane/Tazobactam, Imipenem/Relebactam and Comparators Against Clinical MDR and DTR non-Morganellaceae Enterobacterales and Pseudomonas Aeruginosa Stratified by Patient Age and Hospital Ward: SMART United States 2020-2022. M. Wise. Abstract #1518, Poster Session: Treatment of Antimicrobial Resistant Infections About Clesrovimab (MK-1654) Clesrovimab (MK-1654) is an investigational, extended half-life monoclonal antibody (mAb) developed as a passive immunization for the prevention of RSV. Clesrovimab is designed to be administered as the same single dose, regardless of birth weight, and is being studied in healthy pre-term, full-term and at-risk infants to provide direct, rapid and durable protection through their first RSV season against mild, moderate and severe RSV. About CAPVAXIVE CAPVAXIVE is Merck’s approved 21-valent pneumococcal conjugate vaccine indicated for active immunization for the prevention of invasive disease and pneumonia in adults 18 years of age and older. CAPVAXIVE is specifically designed to help address Streptococcus pneumoniae serotypes predominantly responsible for adult invasive pneumococcal disease (IPD), including eight unique serotypes, 15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B compared to other pneumococcal vaccines. CAPVAXIVE is administered as a single dose. Select Safety Information for CAPVAXIVE Do not administer CAPVAXIVE to individuals with a history of a severe allergic reaction (eg, anaphylaxis) to any component of CAPVAXIVE or to diphtheria toxoid. Individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have a reduced immune response to CAPVAXIVE. The most commonly reported (>10%) solicited adverse reactions in individuals 18 through 49 years of age who received CAPVAXIVE were: injection-site pain (73.1%), fatigue (36.0%), headache (27.5%), myalgia (16.4%), injection-site erythema (13.8%), and injection-site swelling (13.3%). The most commonly reported (>10%) solicited adverse reactions in individuals 50 years of age and older who received CAPVAXIVE were: injection-site pain (41.2%), fatigue (19.7%), and headache (11.0%). Vaccination with CAPVAXIVE may not protect all vaccine recipients. Authorized Use of LAGEVRIO™ (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 Email: dpoc.usa@merck.com Indications for PREVYMIS® (letermovir) PREVYMIS is indicated for prophylaxis of cytomegalovirus (CMV) infection and disease in adult and pediatric patients 6 months of age and older and weighing at least 6 kg who are CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT). PREVYMIS is indicated for prophylaxis of CMV disease in adult and pediatric patients 12 years of age and older and weighing at least 40 kg who are kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]). Selected Safety Information for PREVYMIS Contraindications PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids. Increased pimozide concentrations may lead to QT prolongation and torsades de pointes. Increased ergot alkaloids concentrations may lead to ergotism. PREVYMIS is contraindicated with pitavastatin and simvastatin when co-administered with cyclosporine. Significantly increased pitavastatin or simvastatin concentrations may lead to myopathy or rhabdomyolysis. Warnings and Precautions The concomitant use of PREVYMIS and certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (PREVYMIS or concomitant drugs) or reduced therapeutic effect of PREVYMIS or the concomitant drug. Intravenous formulation of PREVYMIS contains the excipient hydroxypropyl betadex. PREVYMIS injection should be used only in patients unable to take oral therapy and patients should be switched to oral PREVYMIS as soon as they are able to take oral medications. If possible, intravenous administration should not exceed 4 weeks. In patients with renal impairment, accumulation of hydroxypropyl betadex may occur. In adult patients with CLcr less than 50 mL/min and in pediatric patients with a similar degree of renal impairment (based on age-appropriate assessment of renal function) receiving PREVYMIS injection, closely monitor serum creatinine levels. Animal studies have shown the potential for hydroxypropyl betadex to cause ototoxicity. The active ingredient, letermovir, is not known to be associated with ototoxicity. Adverse Reactions The rate of adverse events occurring in at least 10% of adult HSCT recipients treated with PREVYMIS and at a frequency at least 2% greater than placebo were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%). Hypersensitivity reaction, with associated moderate dyspnea, occurred in one adult HSCT recipient following the first infusion of IV PREVYMIS after switching from oral PREVYMIS, leading to treatment discontinuation. The most common adverse event occurring in at least 10% of adult kidney transplant recipients treated with PREVYMIS and at a frequency greater than valganciclovir was diarrhea (32% vs 29%). The safety profile of PREVYMIS in pediatric subjects was consistent with the safety profile observed in clinical trials of PREVYMIS in adults. Drug Interactions If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily in adult and pediatric patients 12 years of age and older. If PREVYMIS is co-administered with cyclosporine in pediatric patients less than 12 years of age, dose adjustment may be required. Co-administration of PREVYMIS may alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PREVYMIS. Consult the full Prescribing Information prior to and during treatment for potential drug interactions. Closely monitor serum creatinine levels in patients with CLcr less than 50 mL/min using PREVYMIS injection. PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment. Use in Specific Populations The safety and effectiveness of PREVYMIS have not been established for: HSCT recipients less than 6 months of age or weighing less than 6 kg, or Kidney transplant recipients less than 12 years of age or weighing less than 40 kg. For patients with creatinine clearance (CLcr) greater than 10 mL/min (by Cockcroft-Gault equation), no dosage adjustment of PREVYMIS is required based on renal impairment. The safety of PREVYMIS in patients with end-stage renal disease (CLcr less than 10 mL/min), including patients on dialysis, is unknown. Following the completion of PREVYMIS prophylaxis, monitoring for CMV reactivation in HSCT recipients is recommended. Indications and usage for RECARBRIO™ (imipenem, cilastatin, and relebactam) RECARBRIO is indicated for the treatment of patients 18 years of age and older with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by the following susceptible gram-negative microorganisms: Acinetobacter calcoaceticus-baumannii complex, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens . RECARBRIO is indicated in patients 18 years of age and older who have limited or no alternative treatment options, for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, caused by the following susceptible gram-negative microorganisms: Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae , and Pseudomonas aeruginosa . RECARBRIO is indicated in patients 18 years of age and older who have limited or no alternative treatment options for the treatment of complicated intra-abdominal infections (cIAI) caused by the following susceptible gram-negative microorganisms: Bacteroides caccae, Bacteroides fragilis, Bacteroides ovatus, Bacteroides stercoris, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Fusobacterium nucleatum, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Parabacteroides distasonis , and Pseudomonas aeruginosa . Approval of the cUTI and cIAI indications is based on limited clinical safety and efficacy data for RECARBRIO. Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of RECARBRIO and other antibacterial drugs, RECARBRIO should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Selected Safety Information for RECARBRIO Hypersensitivity Reactions : RECARBRIO is contraindicated in patients with a history of known severe hypersensitivity (severe systemic allergic reaction such as anaphylaxis) to any component of RECARBRIO. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. Before initiating therapy with RECARBRIO, careful inquiry should be made concerning previous hypersensitivity reactions to carbapenems, penicillins, cephalosporins, other beta-lactams, and other allergens. If a hypersensitivity reaction to RECARBRIO occurs, discontinue the therapy immediately. Seizures and Other Central Nervous System (CNS) Adverse Reactions : CNS adverse reactions, such as seizures, confusional states, and myoclonic activity, have been reported during treatment with imipenem/cilastatin, a component of RECARBRIO, especially when recommended dosages of imipenem were exceeded. These have been reported most commonly in patients with CNS disorders (eg, brain lesions or history of seizures) and/or compromised renal function. Anticonvulsant therapy should be continued in patients with known seizure disorders. If CNS adverse reactions including seizures occur, patients should undergo a neurological evaluation to determine whether RECARBRIO should be discontinued. Increased Seizure Potential Due to Interaction with Valproic Acid : Concomitant use of RECARBRIO, with valproic acid or divalproex sodium may increase the risk of breakthrough seizures. Avoid concomitant use of RECARBRIO with valproic acid or divalproex sodium or consider alternative antibacterial drugs other than carbapenems. Clostridioides difficile –Associated Diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including RECARBRIO, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C difficile may need to be discontinued. Development of Drug-Resistant Bacteria : Prescribing RECARBRIO in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Adverse Reactions : The most frequently reported adverse reactions occurring in ≥5% of HABP/VABP patients treated with RECARBRIO were aspartate aminotransferase increased (11.7%), anemia (10.5%), alanine aminotransferase increased (9.8%), diarrhea (7.9%), hypokalemia (7.9%), and hyponatremia (6.4%). The most frequently reported adverse reactions occurring in ≥2% of cUTI and cIAI patients treated with RECARBRIO were diarrhea (6%), nausea (6%), headache (4%), vomiting (3%), alanine aminotransferase increased (3%), aspartate aminotransferase increased (3%), phlebitis/infusion site reactions (2%), pyrexia (2%), and hypertension (2%). Indications and usage for ZERBAXA® (ceftolozane and tazobactam) ZERBAXA is indicated for the treatment of adult patients (18 years and older) with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by the following susceptible Gram-negative microorganisms: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa , and Serratia marcescens . ZERBAXA is indicated for the treatment of adult and pediatric patients (birth to less than 18 years old) with complicated urinary tract infections (cUTI), including pyelonephritis, caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis , and Pseudomonas aeruginosa . ZERBAXA used in combination with metronidazole is indicated for the treatment of adult and pediatric patients (birth to less than 18 years old) with complicated intra-abdominal infections (cIAI) caused by the following susceptible Gram-negative and Gram-positive microorganisms: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus , and Streptococcus salivarius . Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZERBAXA and other antibacterial drugs, ZERBAXA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Important Safety Information for ZERBAXA Patients with renal impairment : Decreased efficacy of ZERBAXA has been observed in patients with baseline CrCl of 30 to <50 mL/min. In a clinical trial of adult patients, patients with cIAIs with CrCl >50 mL/min had a clinical cure rate of 85.2% when treated with ZERBAXA plus metronidazole vs 87.9% when treated with meropenem. In the same trial, patients with CrCl 30 to <50 mL/min had a clinical cure rate of 47.8% when treated with ZERBAXA plus metronidazole vs 69.2% when treated with meropenem. A similar trend was also seen in the cUTI trial. Dose adjustment is required for adult patients with CrCl 50 mL/min or less. All doses of ZERBAXA are administered over 1 hour. Monitor CrCl at least daily in patients with changing renal function and adjust the dose of ZERBAXA accordingly. Hypersensitivity : ZERBAXA is contraindicated in patients with known serious hypersensitivity to the components of ZERBAXA (ceftolozane/tazobactam), piperacillin/tazobactam, or other members of the beta-lactam class. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials. Before initiating therapy with ZERBAXA, make careful inquiry about previous hypersensitivity reactions to cephalosporins, penicillins, or other beta-lactams. If an anaphylactic reaction to ZERBAXA occurs, discontinue use and institute appropriate therapy. Clostridioides difficile -associated diarrhea (CDAD) , ranging from mild diarrhea to fatal colitis, has been reported with nearly all systemic antibacterial agents, including ZERBAXA. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is confirmed, antibacterial use not directed against C. difficile should be discontinued, if possible. Development of drug-resistant bacteria : Prescribing ZERBAXA in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and risks the development of drug-resistant bacteria. Adverse reactions in adult patients with HABP/VABP : The most common adverse reactions occurring in ≥5% of adult patients receiving ZERBAXA in the HABP/VABP trial were hepatic transaminase increased (11.9%), renal impairment/renal failure (8.9%), and diarrhea (6.4%). Adverse reactions in adult patients with cIAI or cUTI : The most common adverse reactions occurring in ≥5% of adult patients receiving ZERBAXA in the cUTI and cIAI trials were headache (5.8%) in the cUTI trial, and nausea (7.9%), diarrhea (6.2%), and pyrexia (5.6%) in the cIAI trial. Adverse reactions in pediatric patients with cIAI or cUTI : The most common adverse reactions occurring in ≥7% of pediatric patients receiving ZERBAXA in the cIAI trial were diarrhea (17%), thrombocytosis (16%), pyrexia (13%), abdominal pain (11%), vomiting (10%), increased aspartate aminotransferase (7%), and anemia (7%). The most common adverse reactions occurring in ≥7% of pediatric patients receiving ZERBAXA in the cUTI trial were thrombocytosis (9%), leukopenia (8%), diarrhea (7%), and pyrexia (7%). Pediatric Use : There is insufficient information to recommend dosage adjustment for pediatric patients younger than 18 years of age with cIAI and cUTI with eGFR 50 mL/min/1.73m2 or less. ZERBAXA is not recommended in pediatric patients who have an eGFR 50 mL/min/1.73m2 or less. Pediatric patients born at term or pre-term may not have an eGFR of 50 mL/min/1.73m2 or greater at birth or within the first few months of life. 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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 ). Please see Prescribing Information for CAPVAXIVE (Pneumococcal 21-valent Conjugate Vaccine) at https://www.merck.com/product/usa/pi_circulars/c/capvaxive/capvaxive_pi.pdf and Patient Information/Medication Guide for CAPVAXIVE at https://www.merck.com/product/usa/pi_circulars/c/capvaxive/capvaxive_ppi.pdf Before prescribing LAGEVRIO (molnupiravir) please read the Fact Sheet for Healthcare Providers, including Mandatory Requirements for Administration of Molnupiravir 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 Please see Prescribing Information for PREVYMIS (letermovir) at https://www.merck.com/product/usa/pi_circulars/p/prevymis/prevymis_pi.pdf , Patient Information/Medication Guide for PREVYMIS at https://www.merck.com/product/usa/pi_circulars/p/prevymis/prevymis_ppi.pdf and Instructions for Use for PREVYMIS at https://www.merck.com/product/usa/pi_circulars/p/prevymis/prevymis_ifu.pdf Please see Prescribing Information for RECARBRIO (imipenem, cilastatin, and relebactam) at https://www.merck.com/product/usa/pi_circulars/r/recarbrio/recarbrio_pi.pdf Please see Prescribing Information for ZERBAXA (ceftolozane and tazobactam) at https://www.merck.com/product/usa/pi_circulars/z/zerbaxa/zerbaxa_pi.pdf