Ceftolozane Sulfate/Tazobactam Sodium

October 9, 2024 6:45 am ET Merck Underscores Continued Commitment to Fighting Infectious Diseases with More than 40 Data Presentations Across Vaccines, Antibacterials and Antivirals, Including Respiratory Syncytial Virus, Pneumococcal Disease and HIV For the First Time, Full Results will be Highlighted from the Phase 2b/3 Trial of Clesrovimab (MK-1654), an Investigational Respiratory Syncytial Virus Preventative Monoclonal Antibody for Infants 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. 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., USA 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 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 ). 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 Media Contacts: Julie Cunningham (617) 519-6264 Courtney Ronaldo (908) 442-5695 Investor Contacts: Peter Dannenbaum (732) 594-1579 Alexis Constantine (732) 594-1578 Source: Merck & Co., Inc.

RAHWAY, N.J.--( BUSINESS WIRE )--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced financial results for the second quarter of 2024. “ Our business is demonstrating strong momentum as we exit the first half of the year,” said Robert M. Davis, chairman and chief executive officer, Merck. “ Through excellent scientific, commercial and operational execution, we’re achieving significant milestones for our company and for patients, including the launch of WINREVAIR. I am proud of our dedicated teams around the world that are working tirelessly to advance our deep pipeline as we continue delivering innovation that solves unmet medical needs.” Financial Summary $ in millions, except EPS amounts Second Quarter 2024 2023 Change Change Ex- Exchange Sales $16,112 $15,035 7% 11% GAAP net income (loss) 1 5,455 (5,975) N/M N/M Non-GAAP net income (loss) that excludes certain items 1,2* 5,809 (5,220) N/M N/M GAAP EPS 2.14 (2.35) N/M N/M Non-GAAP EPS that excludes certain items 2* 2.28 (2.06) N/M N/M *Refer to table on page 7. N/M – Not meaningful For the second quarter of 2024, Generally Accepted Accounting Principles (GAAP) earnings per share (EPS) assuming dilution was $2.14 and non-GAAP EPS was $2.28. GAAP and non-GAAP loss per share for the second quarter of 2023 include a charge of $4.02 per share for the acquisition of Prometheus Biosciences, Inc. (Prometheus). Non-GAAP EPS in both periods excludes acquisition- and divestiture-related costs, costs related to restructuring programs, as well as income and losses from investments in equity securities. Non-GAAP EPS in the second quarter of 2024 also excludes a tax benefit due to a reduction in reserves for unrecognized income tax benefits, resulting from the expiration of the statute of limitations for assessments related to the 2019 federal tax return year. Year-to-date results can be found in the attached tables. Second-Quarter Sales Performance The following table reflects sales of the company’s top products and significant performance drivers. Second Quarter $ in millions 2024 2023 Change Change Ex-Exchange Commentary Total Sales $16,112 $15,035 7% 11% Approximately 2 percentage points of the negative impact of foreign exchange was due to devaluation of Argentine peso, which was largely offset by inflation-related price increases, consistent with practice in that market. Pharmaceutical 14,408 13,457 7% 11% Increase driven by growth in oncology, cardiovascular and vaccines, partially offset by declines in diabetes and virology. KEYTRUDA 7,270 6,271 16% 21% Growth driven by increased global uptake in earlier-stage indications, including triple-negative breast cancer (TNBC) and renal cell carcinoma, as well as non-small cell lung cancer in the U.S., and continued strong global demand from metastatic indications. Approximately 4 percentage points of the negative impact of foreign exchange was due to devaluation of Argentine peso, which was largely offset by inflation-related price increases. GARDASIL/GARDASIL 9 2,478 2,458 1% 4% Growth primarily due to higher sales in the U.S. driven by higher pricing, demand and public-sector buying patterns, as well as higher demand in certain ex-U.S. markets. Growth was largely offset by lower sales in China due to timing of shipments compared with prior year. JANUVIA/JANUMET 629 864 -27% -23% Decline primarily due to lower pricing and demand in the U.S., as well as ongoing generic competition in many international markets, particularly in Europe and the Asia Pacific region. PROQUAD, M-M-R II and VARIVAX 617 582 6% 7% Growth largely from higher pricing and demand in the U.S. BRIDION 455 502 -9% -8% Decline primarily due to generic competition in certain ex-U.S. markets, particularly in Europe and the Asia Pacific region, partially offset by higher demand in the U.S. Lynparza* 317 310 2% 4% Growth due to higher demand in the U.S. and certain international markets, particularly in China and Europe. Lenvima* 249 242 3% 4% Growth primarily from higher demand in the U.S. VAXNEUVANCE 189 168 13% 16% Growth largely driven by continued uptake from launches in Japan and Europe, partially offset by lower demand and public-sector buying patterns in the U.S. PREVYMIS 188 143 31% 35% Growth primarily due to higher global demand, particularly in the U.S., China and Europe. ROTATEQ 163 131 25% 26% Growth primarily due to timing of shipments to China and public-sector buying patterns in the U.S., partially offset by lower demand in the U.S. WELIREG 126 50 150% 150% Growth primarily driven by higher demand in the U.S., largely attributable to launch of a new indication. LAGEVRIO 110 203 -46% -42% Decline due to lower demand and pricing in certain markets in the Asia Pacific region, partially offset by higher demand in Japan and the U.S. WINREVAIR 70 - - - Represents sales in the U.S. following approval in March 2024. About 40% of sales were attributable to doses administered to patients and remainder was due to distributors building inventory in support of increasing demand. Animal Health 1,482 1,456 2% 6% Growth primarily driven by higher pricing in both Livestock and Companion Animal product portfolios, as well as higher demand for Livestock products, partially offset by a decline in Companion Animal distributor inventory. Approximately 3 percentage points of the negative impact of foreign exchange was due to devaluation of Argentine peso, which was largely offset by inflation-related price increases. Livestock 837 807 4% 11% Growth primarily driven by higher demand for ruminant and poultry products, as well as higher pricing across product portfolio. Companion Animal 645 649 -1% 1% Sales were relatively flat compared with prior year reflecting lower distributor inventory, largely offset by higher pricing across product portfolio. Sales of BRAVECTO were $331 million and $326 million in current and prior-year quarters, respectively, which represented growth of 2%, or 3% excluding impact of foreign exchange. Other Revenues** 222 122 82% 53% Growth primarily due to higher royalty income and favorable impact of revenue hedging activities. *Alliance revenue for this product represents Merck’s share of profits, which are product sales net of cost of sales and commercialization costs. **Other revenues are comprised primarily of revenues from third-party manufacturing arrangements and miscellaneous corporate revenues, including revenue hedging activities. Second-Quarter Expense, EPS and Related Information The table below presents selected expense information. $ in millions GAAP Acquisition- and Divestiture- Related Costs 3 Restructuring Costs (Income) Loss From Investments in Equity Securities Non- GAAP 2 Second Quarter 2024 Cost of sales $3,745 $606 $66 $- $3,073 Selling, general and administrative 2,739 24 31 - 2,684 Research and development 3,500 20 - - 3,480 Restructuring costs 80 - 80 - - Other (income) expense, net 42 (17) - (49) 108 Second Quarter 2023 Cost of sales $4,024 $467 $32 $- $3,525 Selling, general and administrative 2,702 25 52 - 2,625 Research and development 13,321 9 1 - 13,311 Restructuring costs 151 - 151 - - Other (income) expense, net 172 (3) - 194 (19) GAAP Expense, EPS and Related Information Gross margin was 76.8% for the second quarter of 2024 compared with 73.2% for the second quarter of 2023. The increase was primarily due to the favorable impact of product mix (including lower royalty rates related to KEYTRUDA and GARDASIL/GARDASIL 9), partially offset by higher amortization of intangible assets. Selling, general and administrative (SG&A) expenses were $2.7 billion in the second quarter of 2024, an increase of 1% compared with the second quarter of 2023. The increase was primarily due to higher administrative and promotional costs, largely offset by the favorable impact of foreign exchange and lower restructuring costs. Research and development (R&D) expenses were $3.5 billion in the second quarter of 2024 compared with $13.3 billion in the second quarter of 2023. The decrease was primarily due to a $10.2 billion charge in the second quarter of 2023 for the acquisition of Prometheus, partially offset by higher clinical development spending and increased compensation and benefit costs. Other (income) expense, net, was $42 million of expense in the second quarter of 2024 compared with $172 million of expense in the second quarter of 2023. The decrease was primarily due to income from investments in equity securities in 2024 compared with losses in 2023, partially offset by higher net interest expense in 2024. The effective tax rate of 9.1% for the second quarter of 2024 includes a 4.3 percentage point favorable impact due to a reduction in reserves for unrecognized income tax benefits, resulting from the expiration of the statute of limitations for assessments related to the 2019 federal tax return year. GAAP EPS was $2.14 for the second quarter of 2024 compared with GAAP loss per share of $2.35 for the second quarter of 2023. GAAP loss per share in the second quarter of 2023 includes a charge of $4.02 per share for the acquisition of Prometheus. Non-GAAP Expense, EPS and Related Information Non-GAAP gross margin was 80.9% for the second quarter of 2024 compared with 76.6% for the second quarter of 2023. The increase was primarily due to the favorable impact of product mix (including lower royalty rates related to KEYTRUDA and GARDASIL/GARDASIL 9). Non-GAAP SG&A expenses were $2.7 billion in the second quarter of 2024, an increase of 2% compared with the second quarter of 2023. The increase was primarily due to higher administrative and promotional costs, largely offset by the favorable impact of foreign exchange. Non-GAAP R&D expenses were $3.5 billion in the second quarter of 2024 compared with $13.3 billion in the second quarter of 2023. The decrease was primarily due to a $10.2 billion charge in the second quarter of 2023 for the acquisition of Prometheus, partially offset by higher clinical development spending and increased compensation and benefit costs. Non-GAAP other (income) expense, net, was $108 million of expense in the second quarter of 2024 compared with $19 million of income in the second quarter of 2023, primarily due to higher net interest expense. The non-GAAP effective tax rate was 14.1% for the second quarter of 2024. Non-GAAP EPS was $2.28 for the second quarter of 2024 compared with non-GAAP loss per share of $2.06 for the second quarter of 2023. Non-GAAP loss per share in the second quarter of 2023 includes a charge of $4.02 per share for the acquisition of Prometheus. A reconciliation of GAAP to non-GAAP net income (loss) and EPS is provided in the table that follows. Second Quarter $ in millions, except EPS amounts 2024 2023 EPS GAAP EPS $2.14 $(2.35) Difference 0.14 0.29 Non-GAAP EPS that excludes items listed below 2 $2.28 $(2.06) Net Income (Loss) GAAP net income (loss) 1 $5,455 $(5,975) Difference 354 755 Non-GAAP net income (loss) that excludes items listed below 1,2 $5,809 $(5,220) Excluded Items: Acquisition- and divestiture-related costs 3 $633 $498 Restructuring costs 177 236 (Income) loss from investments in equity securities (49) 194 Decrease to net income/increase to net loss before taxes 761 928 Income tax (benefit) expense 4 (407) (173) Decrease to net income/increase to net loss $354 $755 Pipeline and Portfolio Highlights In the second quarter, Merck demonstrated further progress in its strong and diverse pipeline, achieving multiple regulatory and clinical milestones. In vaccines, Merck recently received approval from the U.S. Food and Drug Administration (FDA) for CAPVAXIVE, now the first pneumococcal conjugate vaccine specifically designed to address the serotypes responsible for approximately 85% of invasive pneumococcal disease cases in adults age 65 and older, based on the U.S. Centers for Disease Control and Prevention (CDC) data from 2018-2021. The CDC’s Advisory Committee on Immunization Practices (ACIP) unanimously voted to recommend CAPVAXIVE for adults age 65 and older who have not received a pneumococcal conjugate vaccine or whose vaccination history is unknown, for adults 19 to 64 with certain risk conditions, and for adults 19 and older who have started their pneumococcal vaccine series with PCV13. Additionally, shared clinical decision-making is recommended for a supplemental dose of CAPVAXIVE for adults over 65 who completed their vaccine series with both PCV13 and PPSV23. The company also recently announced positive topline results from its Phase 2b/3 trial of clesrovimab (MK-1654), an investigational respiratory syncytial virus (RSV) preventative monoclonal antibody for infants, which met all primary safety and efficacy endpoints. In cardiometabolic disease, Merck continued to make progress in its launch of WINREVAIR in the U.S. As of the end of June, more than 1,000 patients have received WINREVAIR. The company also announced that the European Union’s (EU) Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for WINREVAIR. If approved by the European Commission, WINREVAIR will be the first activin signaling inhibitor therapy for pulmonary arterial hypertension (PAH, World Health Organization [WHO] Group 1) to be approved in Europe, offering a new treatment option for certain adults with this rare, progressive disease. Additional worldwide regulatory filings for WINREVAIR are underway. In oncology, Merck received FDA approval for KEYTRUDA in combination with chemotherapy, followed by KEYTRUDA as a single agent, for the treatment of certain patients with endometrial carcinoma. This marks the 40 th indication for KEYTRUDA in the U.S., reinforcing its importance as a foundational therapy for certain types of cancer. At the 2024 American Society of Clinical Oncology Annual Meeting, new data were presented on four approved oncology medicines and four pipeline candidates in more than 25 types of cancer. In collaboration with Moderna, Inc., Merck announced encouraging three-year follow-up data for V940 (mRNA-4157) in combination with KEYTRUDA for the adjuvant treatment of patients with high-risk stage III and IV melanoma following complete resection. In addition, new Phase 3 data from a study conducted in China and independently led by Kelun-Biotech evaluating sacituzumab tirumotecan (MK-2870/SKB264), an investigational anti-TROP2 antibody-drug conjugate being developed by Merck in collaboration with Kelun-Biotech, were presented in previously treated patients with locally recurrent or metastatic TNBC. Merck Animal Health launched the 12-month injectable formulation of BRAVECTO for use in dogs in a number of markets in Europe for the treatment and persistent killing of fleas (Ctenocephalides felis and Ctenocephalides canis) and ticks (Rhipicephalus sanguineus, Ixodes ricinus, Ixodes hexagonus, and Dermacentor reticulatus). In addition, in July 2024, Merck completed the acquisition of the aqua business of Elanco Animal Health Incorporated. In July 2024, Merck also completed the acquisition of Eyebiotech Limited (EyeBio), which includes the lead candidate Restoret™/MK-3000 that is being evaluated for the treatment of patients with certain retinal diseases, including diabetic macular edema and neovascular age-related macular degeneration, as well as preclinical candidates. And, Merck and Orion Corporation announced the mutual exercise of an option to convert the companies’ ongoing co-development and co-commercialization agreement for opevesostat (MK-5684/ODM-208), an investigational CYP11A1 inhibitor, and other candidates, into an exclusive global license for Merck. Notable recent news releases on Merck’s pipeline and portfolio are provided in the table that follows. Oncology FDA Approved KEYTRUDA Plus Carboplatin and Paclitaxel as Treatment for Adult Patients With Primary Advanced or Recurrent Endometrial Carcinoma, Based on Results From Phase 3 NRG-GY018/KEYNOTE-868 Trial (Read Announcement) FDA Granted Priority Review to Merck’s Application for KEYTRUDA Plus Chemotherapy as First-Line Treatment of Patients With Unresectable Advanced or Metastatic Malignant Pleural Mesothelioma, Based on Results From Phase 3 KEYNOTE-483 Trial; FDA Set Prescription Drug User Fee Act (PDUFA) Date of Sept. 25, 2024 (Read Announcement) Merck Received Positive EU CHMP Opinion for KEYTRUDA Plus Padcev as First-Line Treatment for Patients With Unresectable or Metastatic Urothelial Carcinoma, Based on Results From Phase 3 KEYNOTE-A39/EV-302 Trial (Read Announcement) Moderna and Merck Announced Three-Year Data for mRNA-4157 (V940) in Combination With KEYTRUDA Demonstrated Sustained Improvement in Recurrence-Free Survival and Distant Metastasis-Free Survival Versus KEYTRUDA in Patients With High-Risk Stage III/IV Melanoma Following Complete Resection (Read Announcement) Merck Announced Phase 3 KEYNOTE-522 Trial Met Its Overall Survival (OS) Endpoint in Patients With High-Risk Early-Stage TNBC (Read Announcement) Merck Announced Phase 3 KEYNOTE-811 Trial Met Dual Primary Endpoint of OS as First-Line Treatment in Patients With HER2-Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Read Announcement) Patritumab Deruxtecan Biologics License Application Submission Received Complete Response Letter From FDA Due to Inspection Findings at Third-Party Manufacturer (Read Announcement) Vaccines FDA Approved CAPVAXIVE for Prevention of Invasive Pneumococcal Disease and Pneumococcal Pneumonia in Adults, Based on Results From Four Phase 3 Trials (Read Announcement) CDC’s ACIP Unanimously Recommended CAPVAXIVE for Pneumococcal Vaccination in Appropriate Adults (Read Announcement) Merck Announced Topline Results From Phase 2b/3 Trial of Clesrovimab (MK-1654), an Investigational RSV Preventative Monoclonal Antibody for Infants, Met All Primary Safety and Efficacy Endpoints (Read Announcement) Cardiometabolic Merck Received Positive EU CHMP Opinion for WINREVAIR (sotatercept) in PAH (Read Announcement) Full-Year 2024 Financial Outlook The following table summarizes the company’s full-year financial outlook. Full Year 2024 Updated Prior Sales * $63.4 to $64.4 billion $63.1 to $64.3 billion Non-GAAP Gross margin 2 Approximately 81% Approximately 81% Non-GAAP Operating expenses 2** $26.8 to $27.6 billion $25.2 to $26.1 billion Non-GAAP Other (income) expense, net 2 Approximately $350 million expense Approximately $250 million expense Non-GAAP Effective tax rate 2 15.5% to 16.5% 14.5% to 15.5% Non-GAAP EPS 2*** $7.94 to $8.04 $8.53 to $8.65 Share count (assuming dilution) Approximately 2.54 billion Approximately 2.55 billion *The company does not have any non-GAAP adjustments to sales. **Includes one-time R&D charges of $656 million for Harpoon Therapeutics, Inc. (Harpoon) acquisition and $1.3 billion for EyeBio acquisition. Outlook does not assume any additional significant potential business development transactions. ***Includes one-time charges totaling $0.77 per share for the Harpoon and EyeBio acquisitions. Merck has not provided a reconciliation of forward-looking non-GAAP gross margin, non-GAAP operating expenses, non-GAAP other (income) expense, net, non-GAAP effective tax rate and non-GAAP EPS to the most directly comparable GAAP measures, given it cannot predict with reasonable certainty the amounts necessary for such a reconciliation, including intangible asset impairment charges, legal settlements, and gains and losses from investments in equity securities either owned directly or through ownership interests in investment funds, without unreasonable effort. These items are inherently difficult to forecast and could have a significant impact on the company’s future GAAP results. Merck continues to experience strong global demand for key growth products, particularly in oncology, and despite impacts related to the lower sell out of GARDASIL from Zhifei Biological Products Co., Ltd. (the company’s distributor and commercialization partner in China) into the points of vaccination in the market during the quarter, Merck is raising and narrowing its full-year sales outlook. Merck now expects its full-year sales to be between $63.4 billion and $64.4 billion, including a negative impact of foreign exchange of approximately 3 percentage points, at mid-July 2024 exchange rates. Approximately 2 percentage points of the negative impact of foreign exchange is due to the devaluation of the Argentine peso, which the company expects will largely be offset by inflation-related price increases, consistent with practice in that market. Merck now expects its full-year non-GAAP effective income tax rate to be between 15.5% and 16.5%, which includes an unfavorable impact related to the one-time charge for the acquisition of EyeBio, which is not tax deductible. Merck now expects its full-year non-GAAP EPS to be between $7.94 and $8.04, including one-time charges of $0.26 and $0.51 per share for the acquisitions of Harpoon and EyeBio, respectively. The outlook includes a negative impact of foreign exchange of more than $0.30 per share. The negative impact of foreign exchange is primarily due to the devaluation of the Argentine peso, which the company expects will largely be offset by inflation-related price increases, consistent with practice in that market. This revised non-GAAP EPS range reflects the following items, which were not previously included in the outlook: A charge of $1.3 billion, or $0.51 per share, for the acquisition of EyeBio. Estimated 2024 expense of approximately $0.09 per share to be incurred to finance the EyeBio and Elanco aqua business acquisitions and to advance the acquired assets. Consistent with past practice, the financial outlook does not assume additional significant potential business development transactions. Non-GAAP EPS excludes acquisition- and divestiture-related costs, costs related to restructuring programs, income and losses from investments in equity securities, as well as a tax benefit in 2024 due to a reduction in reserves for unrecognized income tax benefits, resulting from the expiration of the statute of limitations for assessments related to the 2019 federal tax return year. Earnings Conference Call Investors, journalists and the general public may access a live audio webcast of the earnings conference call on Tuesday, July 30, at 9 a.m. ET via this weblink . A replay of the webcast, along with the sales and earnings news release, supplemental financial disclosures, and slides highlighting the results, will be available at www.merck.com . All participants may join the call by dialing (800) 779-0641 (U.S. and Canada Toll-Free) or (517) 308-9147 and using the access code 4761229. 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., USA 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 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 ). Appendix Generic product names are provided below. Pharmaceutical BRIDION (sugammadex) CAPVAXIVE (Pneumococcal 21-valent Conjugate Vaccine) GARDASIL ( Human Papillomavirus Quadrivalent [Types 6, 11, 16 and 18] Vaccine, Recombinant ) GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) JANUMET (sitagliptin and metformin HCl) JANUVIA (sitagliptin) KEYTRUDA (pembrolizumab) LAGEVRIO (molnupiravir) Lenvima (lenvatinib) Lynparza ( olaparib) M-M-R II (Measles, Mumps and Rubella Virus Vaccine Live) PREVYMIS ( letermovir ) PROQUAD (Measles, Mumps, Rubella and Varicella Virus Vaccine Live) ROTATEQ (Rotavirus Vaccine, Live, Oral, Pentavalent) VARIVAX (Varicella Virus Vaccine Live) VAXNEUVANCE ( Pneumococcal 15-valent Conjugate Vaccine ) WELIREG ( belzutifan ) WINREVAIR (sotatercept-csrk) Animal Health BRAVECTO (fluralaner) _________________________ 1 Net income (loss) attributable to Merck & Co., Inc. 2 Merck is providing certain 2024 and 2023 non-GAAP information that excludes certain items because of the nature of these items and the impact they have on the analysis of underlying business performance and trends. Management believes that providing this information enhances investors’ understanding of the company’s results because management uses non-GAAP results to assess performance. Management uses non-GAAP measures internally for planning and forecasting purposes and to measure the performance of the company along with other metrics. In addition, annual employee compensation, including senior management’s compensation, is derived in part using a non-GAAP pretax income metric. This information should be considered in addition to, but not as a substitute for or superior to, information prepared in accordance with GAAP. For a description of the non-GAAP adjustments, see Table 2a attached to this release. 3 Reflects expenses related to acquisitions of businesses, including the amortization of intangible assets, intangible asset impairment charges and expense or income related to changes in the estimated fair value measurement of liabilities for contingent consideration. Also includes integration, transaction and certain other costs associated with acquisitions and divestitures, as well as amortization of intangible assets related to collaborations and licensing arrangements. 4 Represents the estimated tax impacts on the reconciling items based on applying the statutory rate of the originating territory of the non-GAAP adjustments, as well as a $259 million benefit in the second quarter of 2024, due to a reduction in reserves for unrecognized income tax benefits resulting from the expiration of the statute of limitations for assessments related to the 2019 federal tax return year. MERCK & CO., INC. CONSOLIDATED STATEMENT OF OPERATIONS - GAAP (AMOUNTS IN MILLIONS, EXCEPT PER SHARE FIGURES) (UNAUDITED) Table 1 GAAP % Change GAAP % Change 2Q24 2Q23 June YTD 2024 June YTD 2023 Sales $ 16,112 $ 15,035 7 % $ 31,887 $ 29,522 8 % Costs, Expenses and Other Cost of sales 3,745 4,024 -7 % 7,285 7,951 -8 % Selling, general and administrative 2,739 2,702 1 % 5,221 5,182 1 % Research and development 3,500 13,321 -74 % 7,492 17,597 -57 % Restructuring costs 80 151 -47 % 202 218 -7 % Other (income) expense, net 42 172 -76 % 12 259 -95 % Income (Loss) Before Taxes 6,006 (5,335 ) * 11,675 (1,685 ) * Income Tax Provision 545 637 1,447 1,462 Net Income (Loss) 5,461 (5,972 ) * 10,228 (3,147 ) * Less: Net Income Attributable to Noncontrolling Interests 6 3 11 7 Net Income (Loss) Attributable to Merck & Co., Inc. $ 5,455 $ (5,975 ) * $ 10,217 $ (3,154 ) * Earnings (Loss) per Common Share Assuming Dilution (1) $ 2.14 $ (2.35 ) * $ 4.02 $ (1.24 ) * Average Shares Outstanding Assuming Dilution (1) 2,544 2,539 2,544 2,539 Tax Rate 9.1 % -11.9 % 12.4 % -86.8 % * 100% or greater (1) Because the company recorded a net loss in the second quarter and first six months of 2023, no potential dilutive common shares were used in the computation of loss per common share assuming dilution as the effect would have been anti-dilutive. MERCK & CO., INC. THREE AND SIX MONTHS ENDED JUNE 30, 2024 GAAP TO NON-GAAP RECONCILIATION (AMOUNTS IN MILLIONS, EXCEPT PER SHARE FIGURES) (UNAUDITED) Table 2a GAAP Acquisition and Divestiture-Related Costs (1) Restructuring Costs (2) (Income) Loss from Investments in Equity Securities Certain Other Items Adjustment Subtotal Non-GAAP Second Quarter Cost of sales $ 3,745 606 66 672 $ 3,073 Selling, general and administrative 2,739 24 31 55 2,684 Research and development 3,500 20 20 3,480 Restructuring costs 80 80 80 – Other (income) expense, net 42 (17 ) (49 ) (66 ) 108 Income Before Taxes 6,006 (633 ) (177 ) 49 (761 ) 6,767 Income Tax Provision (Benefit) 545 (129 ) (3) (30 ) (3) 11 (3) (259 ) (4) (407 ) 952 Net Income 5,461 (504 ) (147 ) 38 259 (354 ) 5,815 Net Income Attributable to Merck & Co., Inc. 5,455 (504 ) (147 ) 38 259 (354 ) 5,809 Earnings per Common Share Assuming Dilution $ 2.14 (0.20 ) (0.06 ) 0.02 0.10 (0.14 ) $ 2.28 Tax Rate 9.1 % 14.1 % June YTD Cost of sales $ 7,285 1,069 182 1,251 $ 6,034 Selling, general and administrative 5,221 45 36 81 5,140 Research and development 7,492 36 2 38 7,454 Restructuring costs 202 202 202 – Other (income) expense, net 12 (21 ) (165 ) (186 ) 198 Income Before Taxes 11,675 (1,129 ) (422 ) 165 (1,386 ) 13,061 Income Tax Provision (Benefit) 1,447 (221 ) (3) (72 ) (3) 36 (3) (259 ) (4) (516 ) 1,963 Net Income 10,228 (908 ) (350 ) 129 259 (870 ) 11,098 Net Income Attributable to Merck & Co., Inc. 10,217 (908 ) (350 ) 129 259 (870 ) 11,087 Earnings per Common Share Assuming Dilution $ 4.02 (0.35 ) (0.14 ) 0.05 0.10 (0.34 ) $ 4.36 Tax Rate 12.4 % 15.0 % Only the line items that are affected by non-GAAP adjustments are shown. Merck is providing certain non-GAAP information that excludes certain items because of the nature of these items and the impact they have on the analysis of underlying business performance and trends. Management believes that providing non-GAAP information enhances investors’ understanding of the company’s results because management uses non-GAAP measures to assess performance. Management uses non-GAAP measures internally for planning and forecasting purposes and to measure the performance of the company along with other metrics. In addition, annual employee compensation, including senior management’s compensation, is derived in part using a non-GAAP pretax income metric. The non-GAAP information presented should be considered in addition to, but not as a substitute for or superior to, information prepared in accordance with GAAP. (1) Amounts included in cost of sales primarily reflect expenses for the amortization of intangible assets. Amounts included in selling, general and administrative expenses reflect integration, transaction and certain other costs related to acquisitions and divestitures. Amounts included in research and development expenses primarily reflect the amortization of intangible assets. Amounts included in other (income) expense, net, primarily reflect royalty income related to the prior termination of the Sanofi-Pasteur MSD joint venture. (2) Amounts primarily include employee separation costs and accelerated depreciation associated with facilities to be closed or divested related to activities under the company's formal restructuring programs. (3) Represents the estimated tax impacts on the reconciling items based on applying the statutory rate of the originating territory of the non-GAAP adjustments. (4) Represents a benefit due to a reduction in reserves for unrecognized income tax benefits resulting from the expiration of the statute of limitations for assessments related to the 2019 federal tax return year. MERCK & CO., INC. FRANCHISE / KEY PRODUCT SALES (AMOUNTS IN MILLIONS) (UNAUDITED) Table 3 2024 2023 2Q June YTD 1Q 2Q June YTD 1Q 2Q June YTD 3Q 4Q Full Year Nom % Ex-Exch % Nom % Ex-Exch % TOTAL SALES (1) $15,775 $16,112 $31,887 $14,487 $15,035 $29,522 $15,962 $14,630 $60,115 7 11 8 11 PHARMACEUTICAL 14,006 14,408 28,415 12,721 13,457 26,179 14,263 13,141 53,583 7 11 9 12 Oncology Keytruda 6,947 7,270 14,217 5,795 6,271 12,065 6,338 6,608 25,011 16 21 18 22 Alliance Revenue – Lynparza (2) 292 317 609 275 310 585 299 315 1,199 2 4 4 6 Alliance Revenue – Lenvima (2) 255 249 504 232 242 474 260 226 960 3 4 6 7 Welireg 85 126 211 42 50 92 54 72 218 150 150 128 128 Alliance Revenue – Reblozyl (3) 71 90 161 43 47 90 52 70 212 92 92 80 80 Vaccines (4) Gardasil/Gardasil 9 2,249 2,478 4,727 1,972 2,458 4,430 2,585 1,871 8,886 1 4 7 10 ProQuad/M-M-R II/Varivax 570 617 1,187 528 582 1,109 713 545 2,368 6 7 7 7 Vaxneuvance 219 189 408 106 168 274 214 176 665 13 16 49 51 RotaTeq 216 163 379 297 131 428 156 185 769 25 26 -11 -10 Pneumovax 23 61 59 120 96 92 188 140 85 412 -36 -32 -36 -32 Hospital Acute Care Bridion 440 455 895 487 502 989 424 429 1,842 -9 -8 -9 -8 Prevymis 174 188 362 129 143 273 157 175 605 31 35 33 37 Dificid 73 92 165 65 76 141 74 87 302 20 20 16 16 Zerbaxa 56 62 118 50 54 104 53 61 218 14 18 13 16 Noxafil 56 45 101 60 55 116 51 46 213 -20 -9 -13 -2 Cardiovascular Alliance Revenue - Adempas/Verquvo (5) 98 106 203 99 68 167 92 108 367 56 56 22 22 Adempas (6) 70 72 142 59 65 125 65 66 255 11 15 14 17 Winrevair 70 70 - - - - Virology Lagevrio 350 110 460 392 203 595 640 193 1,428 -46 -42 -23 -18 Isentress/Isentress HD 111 89 200 123 136 259 119 105 483 -35 -31 -23 -19 Delstrigo 56 60 116 44 50 94 54 54 201 19 23 23 26 Pifeltro 42 39 81 34 38 72 37 33 142 3 4 13 13 Neuroscience Belsomra 46 53 99 56 63 119 58 54 231 -16 -8 -17 -10 Immunology Simponi 184 172 356 180 180 359 179 171 710 -4 -2 -1 -1 Remicade 39 35 74 51 48 99 45 43 187 -27 -20 -25 -21 Diabetes (7) Januvia 419 405 824 551 511 1,062 581 547 2,189 -21 -16 -22 -19 Janumet 251 224 475 329 354 683 255 240 1,177 -37 -32 -30 -26 Other Pharmaceutical (8) 576 573 1,151 626 560 1,187 568 576 2,333 2 6 -3 -1 ANIMAL HEALTH 1,511 1,482 2,993 1,491 1,456 2,947 1,400 1,278 5,625 2 6 2 5 Livestock 850 837 1,686 849 807 1,656 874 808 3,337 4 11 2 7 Companion Animal 661 645 1,307 642 649 1,291 526 470 2,288 -1 1 1 3 Other Revenues (9) 258 222 479 275 122 396 299 211 907 82 53 21 24 Sum of quarterly amounts may not equal year-to-date amounts due to rounding. (1) Only select products are shown. (2) Alliance Revenue represents Merck’s share of profits, which are product sales net of cost of sales and commercialization costs. (3) Alliance Revenue represents royalties. (4) Total Vaccines sales were $3,424 million and $3,656 million in the first and second quarter of 2024, respectively, and $3,133 million and $3,557 million in the first and second quarter of 2023, respectively. (5) Alliance Revenue represents Merck's share of profits from sales in Bayer's marketing territories, which are product sales net of cost of sales and commercialization costs. (6) Net product sales in Merck's marketing territories. (7) Total Diabetes sales were $745 million and $715 million in the first and second quarter of 2024, respectively, and $950 million and $951 million in the first and second quarter of 2023, respectively. (8) Includes Pharmaceutical products not individually shown above. (9) Other Revenues are comprised primarily of revenues from third-party manufacturing arrangements and miscellaneous corporate revenues, including revenue-hedging activities. Other Revenues related to the receipt of upfront and milestone payments for out-licensed products were $61 million and $15 million in the first and second quarter of 2024, respectively, and $51 million and $3 million in the first and second quarter of 2023, respectively.