Merck Highlights New Data from Cardio-Pulmonary Pipeline at ACC.26 Showcasing Commitment to Advance Innovative Research

Late-breaking presentation of results from the Phase 3 CORALreef AddOn trial evaluating enlicitide decanoate, Merck’s investigational oral PCSK9 inhibitor, which may help address the cardiovascular (CV) epidemic

Data from the Phase 2 CADENCE trial of WINREVAIR^TM (sotatercept-csrk) in patients with the syndrome of combined post- and precapillary pulmonary hypertension and heart failure with preserved ejection fraction (CpcPH-HFpEF) to be featured as late-breaking presentation

RAHWAY, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced new clinical data from the company’s cardio-pulmonary pipeline will be presented at the American College of Cardiology’s Annual Scientific Session and Expo (ACC.26) in New Orleans, La., from March 28-30. The results shared will highlight Merck’s unwavering commitment to advancing innovative research in hypercholesterolemia and in the syndrome of combined post- and precapillary pulmonary hypertension and heart failure with preserved ejection fraction (CpcPH-HFpEF) to help address the significant burden of these diseases.

Key data being shared include two late-breaking presentations:

• Positive results from the Phase 3 CORALreef AddOn trial evaluating the efficacy and safety of enlicitide, an investigational, once-daily oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor versus ezetimibe, versus bempedoic acid and versus ezetimibe and bempedoic acid in adults with hypercholesterolemia who are treated with a statin;
• Positive results from the Phase 2 CADENCE trial evaluating WINREVAIR™ (sotatercept-csrk) in adults with CpcPH-HFpEF.

“The data planned for presentation at ACC will underscore the strength and momentum of Merck’s cardio-pulmonary pipeline as we work to advance research that helps address the CV epidemic impacting millions with atherosclerosis, as well as CpcPH-HFpEF, a distinct syndrome with limited treatment options,” said Dr. Joerg Koglin, senior vice president, head of general and specialty medicine, global clinical development, Merck Research Laboratories. “Building on our history of bringing forward innovative therapies in heart and lung disease, we are proud to share research at ACC.26 that improves our understanding of these serious diseases and has the potential to help patients around the world.”

Details on Merck abstracts at ACC.26:

Hypercholesterolemia and ASCVD
Phase 1 update: the novel oral PCSK9 inhibitor enlicitide does not affect the pharmacokinetics of narrow therapeutic index concomitant medications. D. Johns.	Abstract #1302-039; Cardiovascular Disease Prevention 01 on Saturday, March 28, 10:30 a.m. ET/9:30 a.m. CT
Women are less likely than men to receive add-on nonstatin lipid-lowering therapy (LLT) and to adhere to LLT: A systematic review. A. Victores.	Abstract #1374-058; Cardiovascular Disease Prevention 04 on Saturday, March 28, 3:00 p.m. ET/2:00 p.m. CT
Association between LDL-C lowering and reduced risk of cardiovascular events: An updated systemic review and meta-regression. X. Zhang.	Abstract #1446-052; Cardiovascular Disease Prevention 07 on Sunday, March 29, 12:00 p.m. ET/11:00 a.m. CT
Patient characteristics and outcomes vary by atherosclerotic cardiovascular disease phenotype: clinical implications of real-world data from England. A. Watanabe.	Abstract #1446-050; Cardiovascular Disease Prevention 07 on Sunday, March 29, 12:00 p.m. ET/11:00 a.m. CT
Findings from the LISTEN-LDL-US (lipid lowering therapy insights patient survey on treatment experiences and needs in the United States) study. A. Victores.	Abstract #1469-056; Cardiovascular Disease Prevention 08 on Sunday, March 29, 1:30 p.m. ET/12:30 p.m. CT
Durability of enlicitide for lipid lowering: on-treatment analysis of data from CORALreef Lipids and CORALreef HeFH trials. A. Navar.	Abstract #276-08; Featured Clinical Research III on Sunday, March 29, 1:35 p.m. ET/12:35 p.m. CT
Efficacy and safety of enlicitide decanoate, an oral macrocyclic peptide inhibitor of PCSK9, compared with bempedoic acid, ezetimibe, or bempedoic acid co-administered with ezetimibe in statin-treated adults with hypercholesterolemia: Phase 3 CORALreef AddOn trial. A. Catapano.	Abstract #336-07; Investigative Horizons I on Monday, March 30, 11:45 a.m. ET/10:45 a.m. CT

CpcPH-HFpEF
Efficacy and safety of sotatercept in combined post- and pre-capillary pulmonary hypertension associated with heart failure with preserved ejection fraction: results from the Phase 2 CADENCE trial. M. Gomberg-Maitland.	Abstract #107-09; Late-Breaking Clinical Trials IV on Sunday, March 29, 12:00 p.m. ET/11:00 a.m. CT

About enlicitide and PCSK9

Enlicitide has the potential to be the first approved oral PCSK9 inhibitor. It is designed to lower LDL-C via the same biological mechanism as currently approved monoclonal antibody, injectable PCSK9 inhibitors but in a daily pill form. Enlicitide is an investigational novel macrocyclic peptide that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors.

PCSK9 plays a key role in cholesterol homeostasis by regulating levels of the LDL receptor, which is responsible for the uptake of cholesterol into cells. Inhibition of PCSK9 is designed to prevent the interaction of PCSK9 with LDL receptors. This results in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood.

About CORALreef Clinical Trial Program

The efficacy and safety profile of enlicitide is being evaluated through the comprehensive CORALreef Clinical Trial program evaluating over 19,000 participants who have hypercholesterolemia. As previously announced, enlicitide demonstrated statistically significant and clinically meaningful reductions in LDL-C in three pivotal Phase 3 studies: CORALreef Lipids (NCT05952856), CORALreef HeFH (NCT05952869) and CORALreef AddOn (NCT06450366). Enlicitide is continuing to be evaluated in the large cardiovascular outcomes trial, CORALreef Outcomes (NCT06008756), which has completed enrollment with over 14,500 participants. Additional CORALreef clinical trials include CORALreef Extension (NCT06492291), CORALreef Pediatric (NCT07058077) and CORALreef Combination (NCT07216482).

About hypercholesterolemia

Hypercholesterolemia, a type of hyperlipidemia, is a disorder in which there are elevated LDL-C levels in the blood. It affects approximately 86 million adults in the U.S. and is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Nearly 70% of people with ASCVD who are treated with lipid lowering therapies do not reach target LDL cholesterol levels. High LDL-C, if left untreated, can lead to ASCVD events such as heart attacks and strokes.

About the CV epidemic and atherosclerotic cardiovascular disease

The silent CV epidemic is the leading cause of deaths globally, contributing to the majority of heart attacks and strokes, and deaths related to CV continue to rise. ASCVD accounts for 85% of CV deaths. It is caused by the buildup of plaque within the arteries, leading to narrowed or blocked blood vessels that can result in serious CV events such as heart attacks and strokes as well as coronary artery disease, peripheral artery disease and cerebrovascular disease.

About WINREVAIR^™ (sotatercept-csrk) for injection, for subcutaneous use, 45 mg, 60 mg

In the U.S., WINREVAIR is FDA-approved for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1 pulmonary hypertension) to improve exercise capacity and World Health Organization (WHO) functional class (FC), and reduce the risk of clinical worsening events, including hospitalization for PAH, lung transplantation and death. WINREVAIR is the first activin signaling inhibitor therapy approved to treat PAH. WINREVAIR improves the balance between pro-proliferative and anti-proliferative signaling to modulate vascular proliferation. In preclinical models, WINREVAIR induced cellular changes that were associated with thinner vessel walls, partial reversal of right ventricular remodeling and improved hemodynamics.

WINREVAIR is the subject of a licensing agreement with Bristol Myers Squibb.

Selected Safety Information for WINREVAIR

WINREVAIR may increase hemoglobin (Hgb). Severe erythrocytosis may increase the risk of thromboembolic events or hyperviscosity syndrome. Monitor Hgb before each dose for the first 5 doses, or longer if values are unstable, and periodically thereafter, to determine if dose adjustments are required.

WINREVAIR may decrease platelet count. Severe thrombocytopenia may increase the risk of bleeding. Thrombocytopenia occurred more frequently in patients also receiving prostacyclin infusion. Do not initiate treatment if platelet count is <50,000/mm³. Monitor platelets before each dose for the first 5 doses, or longer if values are unstable, and periodically thereafter to determine whether dose adjustments are required.

In clinical studies, serious bleeding (e.g., gastrointestinal, intracranial hemorrhage) was reported in 4% vs 1% (STELLAR) and 7% vs 5% (ZENITH) of patients taking WINREVAIR vs placebo, respectively. Patients with serious bleeding were more likely to be on prostacyclin background therapy and/or antithrombotic agents, or have low platelet counts. Advise patients about signs and symptoms of blood loss. Evaluate and treat bleeding accordingly. Do not administer WINREVAIR if the patient is experiencing serious bleeding.

WINREVAIR may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment with WINREVAIR and for at least 4 months after the final dose. Pregnancy testing is recommended for females of reproductive potential before starting WINREVAIR treatment.

Based on findings in animals, WINREVAIR may impair female and male fertility. Advise patients on the potential effects on fertility.

The most common adverse reactions (≥10% for WINREVAIR and at least 5% more than placebo) occurring in the STELLAR Phase 3 clinical trial were headache (24.5% vs 17.5%), epistaxis (22.1% vs 1.9%), rash (20.2% vs 8.1%), telangiectasia (16.6% vs 4.4%), diarrhea (15.3% vs 10.0%), dizziness (14.7% vs 6.3%), and erythema (13.5% vs 3.1%). The most common adverse reactions in the ZENITH trial were infections (67.4% vs 44.2%), epistaxis (45.3% vs 9.3%), diarrhea (25.6% vs 17.4%), telangiectasia (25.6% vs 3.5%), increased hemoglobin (15.1% vs 1.2%), rash (10.5% vs 4.7%), erythema (10.5% vs 3.5%) and gingival bleeding (10.5% vs 2.3%).

Because of the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with WINREVAIR, and for 4 months after the final dose.

About the syndrome of combined post- and precapillary pulmonary hypertension and heart failure with preserved ejection fraction (CpcPH-HFpEF)

Combined post- and precapillary pulmonary hypertension and heart failure with preserved ejection fraction (CpcPH-HFpEF) is a distinct, identifiable and well-characterized condition that develops in people with long-term or advanced heart failure. Different from Group 1 pulmonary arterial hypertension (PAH), CpcPH-HFpEF is caused by two interrelated components: pulmonary vascular disease and cardiac disease. CpcPH-HFpEF is thought to be uncommon and underdiagnosed, typically impacting people who are older and have other comorbid conditions. It is associated with a worse prognosis and higher mortality rate compared to HFpEF alone. There are no treatments specifically approved for CpcPH-HFpEF.

Merck’s focus on cardiometabolic and respiratory diseases

Merck has a long history of developing treatments for cardiometabolic and respiratory diseases. Building on a legacy that began nearly 70 years ago with the introduction of our first cardiovascular therapy, we are committed to advancing research for patients impacted by cardiometabolic and respiratory diseases. Our focus spans a range of diseases, including atherosclerotic cardiovascular disease, heart failure, pulmonary hypertension and chronic obstructive pulmonary disease (COPD).

Advancements in the treatment of cardiometabolic and respiratory diseases can make a critical difference for patients and health systems around the world. At Merck, we strive for scientific excellence and innovation in all stages of research, from discovery through approval and life cycle management. We partner with experts in the community to advance research that can help improve the lives of patients.

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, 2025 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 WINREVAIR (sotatercept-csrk) at http://www.merck.com/product/usa/pi_circulars/w/winrevair/winrevair_pi.pdf and Patient Information for WINREVAIR at http://www.merck.com/product/usa/pi_circulars/w/winrevair/winrevair_ppi.pdf, and Instructions for Use for WINREVAIR (1-vial kit, 2-vial kit) at https://www.merck.com/product/usa/pi_circulars/w/winrevair/winrevair_ifu_1-vial_2-vial_kits.pdf.