Merck Receives European Commission Approval for WINREVAIR™ (sotatercept) in Combination With Other Pulmonary Arterial Hypertension (PAH) Therapies, for the Treatment of PAH in Adult Patients With Functional Class II-III

Rhea-AI Summary

Merck (NYSE: MRK) has received European Commission approval for WINREVAIR™ (sotatercept) to treat adult patients with pulmonary arterial hypertension (PAH) in WHO Functional Class II-III. WINREVAIR is the first activin signaling inhibitor therapy for PAH approved in Europe, designed to improve exercise capacity when used with other PAH therapies.

The approval is based on the Phase 3 STELLAR trial, which showed significant improvements in six-minute walk distance and reduced risk of death or clinical worsening. WINREVAIR demonstrated an 82% reduction in the risk of death or clinical worsening compared to background therapy alone.

WINREVAIR is administered as a subcutaneous injection every 3 weeks and can be self-administered with proper training. This approval is valid in all 27 EU member states, Iceland, Liechtenstein, and Norway.

Positive

• European Commission approval for WINREVAIR to treat PAH in adult patients
• First activin signaling inhibitor therapy for PAH approved in Europe
• Significant improvement in six-minute walk distance of 40.8 meters over placebo in Phase 3 STELLAR trial
• 82% reduction in the risk of death or clinical worsening compared to background therapy alone
• Can be self-administered by patients or caregivers after proper training

Negative

• None.

Insights

Financial Analyst

Merck's approval of WINREVAIR in Europe is a significant milestone for the company's cardiovascular portfolio. As the first activin signaling inhibitor for PAH in Europe, it positions Merck as an innovator in this therapeutic area. The approval covers 27 EU member states plus Iceland, Liechtenstein and Norway, representing a substantial market opportunity. While specific revenue projections aren't provided, the orphan drug designation suggests a potentially lucrative niche market. The 82% reduction in risk of death or clinical worsening is a compelling efficacy data point that could drive adoption. However, investors should note that the impact on Merck's overall financial performance may be gradual, given the relatively small patient population for PAH.

Medical Research Analyst

The approval of WINREVAIR marks a significant advancement in PAH treatment. The 40.8-meter improvement in six-minute walk distance is clinically meaningful, potentially enhancing patients' quality of life. The novel mechanism of action targeting the activin signaling pathway opens new avenues for research in vascular diseases. The 82% reduction in death or clinical worsening risk is particularly impressive, suggesting WINREVAIR could become a new standard of care when combined with existing therapies. The every-3-weeks subcutaneous administration may improve treatment adherence compared to daily oral medications. Future research may explore WINREVAIR's potential in earlier disease stages or in combination with emerging therapies to further improve outcomes in this challenging disease.

Market Research Analyst

WINREVAIR's approval could reshape the PAH market landscape in Europe. As the first-in-class activin signaling inhibitor, it differentiates Merck from competitors in a market dominated by established players. The combination approach with existing therapies suggests WINREVAIR could complement rather than replace current treatments, potentially expanding the overall market size. The PRIME and orphan designations indicate regulatory support and market protection, which could help Merck maintain a strong position. However, market penetration may face challenges due to the established treatment paradigms and potential reimbursement hurdles in different European healthcare systems. The patient/caregiver administration option could be a key selling point, potentially reducing healthcare system burden and improving accessibility.

WINREVAIR is the first activin signaling inhibitor therapy for PAH approved in Europe

RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the European Commission (EC) has approved WINREVAIR™ (sotatercept), in combination with other pulmonary arterial hypertension (PAH) therapies, for the treatment of PAH in adult patients with World Health Organization (WHO) Functional Class (FC) II to III, to improve exercise capacity. WINREVAIR is the first and only activin signaling inhibitor therapy for PAH approved in all 27 member states of the EU, as well as Iceland, Liechtenstein and Norway. WINREVAIR works by improving the balance between pro- and anti-proliferative signaling to regulate vascular cell proliferation underlying PAH. The EC approval of WINREVAIR is based on safety and efficacy results from the Phase 3 STELLAR trial.

“The European Commission’s approval of WINREVAIR is an important step for patients,” said Dr. Joerg Koglin, senior vice president and head of general medicine, global clinical development, Merck Research Laboratories. “WINREVAIR is the first therapy targeting the activin signaling pathway. We are proud to bring this innovative treatment to more patients and remain committed to further investigating the potential of WINREVAIR in areas where there are unmet needs in the management of PAH.”

“Pulmonary arterial hypertension is a devastating disease for patients, who suffer from debilitating symptoms that can severely limit their daily activities,” said Dr. Marc Humbert, Professor of Medicine and Director of the Pulmonary Hypertension Reference Center at Université Paris-Saclay. “New treatment opinions continue to be needed for patients. Based on the Phase 3 STELLAR study, adding WINREVAIR to background PAH therapy improved exercise capacity, reduced the risk of death or clinical worsening events and improved functional class compared to background PAH therapy alone. These findings are significant and reinforce that WINREVAIR, in combination with other PAH therapies, should be considered as a new standard of care for the treatment of functional class II and III adult patients.”

The EC approval is based on the Phase 3 STELLAR trial, which compared WINREVAIR (n=163) to placebo (n=160), both in combination with background standard of care therapies in adult patients with PAH (WHO Group 1, FC II or III). The primary efficacy endpoint was change from baseline at Week 24 in six-minute walk distance. Treatment with WINREVAIR resulted in a statistically significant and clinically meaningful improvement in six-minute walk distance of 40.8 meters over placebo (95% CI: 27.5, 54.1; p<0.001). WINREVAIR also significantly improved multiple important secondary outcome measures, including reducing the risk of death or clinical worsening. In a post hoc analysis provided to EMA, time to death or clinical worsening was defined as the time from randomization to the first occurrence of deterioration of PAH, PAH-specific hospitalization, worsening-related listing for lung and/or heart transplant, need for atrial septostomy, or death from any cause. There was an 82% reduction in the risk of death or clinical worsening with WINREVAIR on top of background therapy versus background therapy alone (number of events: 7 vs 29, HR=0.182; 95% CI: 0.075, 0.441; p<0.001).

WINREVAIR is administered once every 3 weeks as a single injection under the skin and may be administered by patients or caregivers with guidance, training and follow-up from a healthcare provider. Healthcare providers and patients/caregivers should refer to the Instructions for Use for information on the proper preparation and administration of WINREVAIR.

This approval by the EC for WINREVAIR is valid in all 27 member states of the EU, as well as Iceland, Liechtenstein and Norway. WINREVAIR was previously granted Priority Medicines (PRIME) and orphan designation by the EMA for the treatment of PAH.

On March 26, 2024, the FDA approved WINREVAIR in the U.S. for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1) to increase exercise capacity, improve WHO functional class (FC) and reduce the risk of clinical worsening events.

About STELLAR

The STELLAR study (NCT04576988) was a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which 323 patients with PAH (WHO Group 1 FC II or III) were randomized 1:1 to WINREVAIR (target dose 0.7 mg/kg) (n=163) or placebo (n=160) plus stable background therapy administered subcutaneously once every 3 weeks.

The most common PAH etiologies were idiopathic PAH (59%), heritable PAH (18%), and PAH associated with connective tissue diseases (CTD) (15%). Most participants were receiving either three (61%) or two (35%) background drugs for PAH, and 40% were receiving prostacyclin infusions. The mean time from PAH diagnosis was 8.8 years. Patients had a WHO FC II (49%) or III (51%) at baseline.

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

WINREVAIR, the first activin signaling inhibitor therapy approved to treat PAH, 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 in the U.S.

WINREVAIR may increase hemoglobin and lead to erythrocytosis. 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 and lead to severe thrombocytopenia, which 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 if dose adjustments are required.

In clinical studies, serious bleeding (e.g., gastrointestinal, intracranial hemorrhage) was reported in 4% of patients taking WINREVAIR and 1% of patients taking placebo. Serious bleeding was more likely in patients on prostacyclin background therapy and/or antithrombotic agents, or with low platelet counts. Advise patients about signs and symptoms of blood loss. 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 occurring in the Phase 3 clinical trial (≥10% for WINREVAIR and at least 5% more than placebo) 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 6.2%), and erythema (13.5% vs 3.1%).

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 pulmonary arterial hypertension (PAH)

Pulmonary arterial hypertension (PAH) is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation. Approximately 40,000 people in the U.S. and 30,000 people in the EU are living with PAH. The disease progresses rapidly for many patients. PAH results in significant strain on the heart, leading to limited physical activity, heart failure and reduced life expectancy. The five-year mortality rate for patients with PAH is approximately 43%, based on data from the REVEAL registry (patients enrolled between March 2006 and December 2009).

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 WINREVAIR (sotatercept-csrk) at http://www.merck.com/product/usa/pi_circulars/w/winrevair/winrevair_pi.pdf, 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240826216036/en/

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Source: Merck & Co., Inc.

FAQ

What is WINREVAIR and what has Merck (MRK) received approval for?

WINREVAIR (sotatercept) is a new treatment for pulmonary arterial hypertension (PAH). Merck (MRK) has received European Commission approval for WINREVAIR to treat adult PAH patients with WHO Functional Class II-III, in combination with other PAH therapies.

What were the key results of the Phase 3 STELLAR trial for WINREVAIR (MRK)?

The Phase 3 STELLAR trial showed that WINREVAIR improved six-minute walk distance by 40.8 meters over placebo and reduced the risk of death or clinical worsening by 82% compared to background therapy alone.

How is WINREVAIR administered and how often for PAH patients (MRK)?

WINREVAIR is administered as a subcutaneous injection once every 3 weeks. It can be self-administered by patients or caregivers after proper training and guidance from a healthcare provider.

In which countries is the European Commission approval for WINREVAIR (MRK) valid?

The European Commission approval for WINREVAIR is valid in all 27 EU member states, as well as Iceland, Liechtenstein, and Norway.