Merck Announces Decision to Stop Phase 3 HYPERION Trial Evaluating WINREVAIR™ (sotatercept-csrk) Early and Move to Final Analysis
Merck (NYSE: MRK) announced the early termination of its Phase 3 HYPERION trial evaluating WINREVAIR versus placebo in adults with pulmonary arterial hypertension (PAH). The decision was based on positive results from the interim analysis of the ZENITH trial and overall WINREVAIR clinical program data.
The external steering committee and Merck determined it would be unethical to continue the placebo-controlled trial given the robust efficacy data demonstrated across patient populations. This decision will allow all study participants to access WINREVAIR through the Phase 3 SOTERIA open-label extension study.
WINREVAIR is currently approved in the U.S. and 38 countries based on Phase 3 STELLAR trial results. The complete findings from the HYPERION study will be presented at a future medical congress later this year.
Merck (NYSE: MRK) ha annunciato la terminazione anticipata del trial di Fase 3 HYPERION, che valuta WINREVAIR rispetto al placebo negli adulti affetti da ipertensione arteriosa polmonare (PAH). La decisione è stata presa sulla base dei risultati positivi derivanti dall'analisi intermedia del trial ZENITH e dei dati complessivi del programma clinico di WINREVAIR.
Il comitato di monitoraggio esterno e Merck hanno determinato che sarebbe stato eticamente scorretto continuare il trial controllato con placebo, dati i solidi dati di efficacia dimostrati tra le popolazioni di pazienti. Questa decisione permetterà a tutti i partecipanti allo studio di accedere a WINREVAIR attraverso lo studio di estensione open-label di Fase 3 SOTERIA.
WINREVAIR è attualmente approvato negli Stati Uniti e in 38 paesi, sulla base dei risultati del trial di Fase 3 STELLAR. I risultati completi dello studio HYPERION saranno presentati a un prossimo congresso medico entro la fine di quest'anno.
Merck (NYSE: MRK) anunció la finalización anticipada de su ensayo de Fase 3 HYPERION que evalúa WINREVAIR frente al placebo en adultos con hipertensión arterial pulmonar (PAH). La decisión se basó en resultados positivos del análisis intermedio del ensayo ZENITH y en los datos generales del programa clínico de WINREVAIR.
El comité de dirección externo y Merck determinaron que sería poco ético continuar el ensayo controlado con placebo, dado los sólidos datos de eficacia demostrados en diversas poblaciones de pacientes. Esta decisión permitirá a todos los participantes del estudio acceder a WINREVAIR a través del estudio de extensión abierto de Fase 3 SOTERIA.
WINREVAIR está actualmente aprobado en los EE. UU. y en 38 países, basándose en los resultados del ensayo de Fase 3 STELLAR. Los hallazgos completos del estudio HYPERION serán presentados en un congreso médico futuro más adelante este año.
머크 (NYSE: MRK)는 폐동맥 고혈압(PAH) 환자를 대상으로 WINREVAIR와 위약을 비교 평가한 3상 HYPERION 임상시험의 조기 종료를 발표했습니다. 이 결정은 ZENITH 임상시험의 중간 분석 및 WINREVAIR 전체 임상 프로그램 데이터의 긍정적인 결과에 기반하였습니다.
외부 자문위원회와 머크는 환자 집단에서 입증된 강력한 효능 데이터를 고려하여 위약 대조 임상시험을 지속하는 것이 비윤리적이라고 판단했습니다. 이 결정으로 모든 연구 참가자는 3상 SOTERIA 오픈 라벨 확장 연구를 통해 WINREVAIR에 접근할 수 있게 될 것입니다.
WINREVAIR는 현재 미국 및 38개국에서 3상 STELLAR 시험 결과를 바탕으로 승인되었습니다. HYPERION 연구의 전체 결과는 올해 말에 있을 향후 의학 회의에서 발표될 예정입니다.
Merck (NYSE: MRK) a annoncé la fin anticipée de son essai de Phase 3 HYPERION évaluant WINREVAIR par rapport à un placebo chez les adultes atteints d'hypertension artérielle pulmonaire (HTAP). La décision a été fondée sur des résultats positifs provenant de l'analyse intermédiaire de l'essai ZENITH et des données globales du programme clinique WINREVAIR.
Le comité de pilotage externe et Merck ont déterminé qu'il serait contraire à l'éthique de continuer l'essai contrôlé par placebo compte tenu des données d'efficacité solides démontrées dans les populations de patients. Cette décision permettra à tous les participants de l'étude d'accéder à WINREVAIR à travers l'étude d'extension en ouvert de Phase 3 SOTERIA.
WINREVAIR est actuellement approuvé aux États-Unis et dans 38 pays, sur la base des résultats de l'essai de Phase 3 STELLAR. Les résultats complets de l'étude HYPERION seront présentés lors d'un futur congrès médical plus tard cette année.
Merck (NYSE: MRK) hat die vorzeitige Beendigung seiner Phase-3-Studie HYPERION bekannt gegeben, die WINREVAIR im Vergleich zu Placebo bei Erwachsenen mit pulmonaler arterieller Hypertonie (PAH) bewertet. Die Entscheidung basierte auf positiven Ergebnissen der Zwischenanalyse der ZENITH-Studie und den Gesamtdaten des klinischen Programms von WINREVAIR.
Das externe Lenkungskomitee und Merck stellten fest, dass es unethisch wäre, die placebokontrollierte Studie fortzusetzen, angesichts der robusten Wirksamkeitsdaten, die in den Patientengruppen gezeigt wurden. Diese Entscheidung ermöglicht es allen Studienteilnehmern, über die offene Erweiterungsstudie der Phase 3 SOTERIA Zugang zu WINREVAIR zu erhalten.
WINREVAIR ist derzeit in den USA und in 38 Ländern auf der Grundlage der Ergebnisse der Phase-3-STELLAR-Studie zugelassen. Die vollständigen Ergebnisse der HYPERION-Studie werden auf einem zukünftigen medizinischen Kongress später in diesem Jahr vorgestellt.
- WINREVAIR demonstrates robust efficacy data across broad patient spectrum
- Product already approved in U.S. and 38 countries
- Early trial termination allows faster access to treatment for all study participants
- Early termination of Phase 3 trial may limit complete data collection
Insights
The early termination of WINREVAIR's HYPERION trial represents a significant positive development for Merck's PAH franchise. When clinical trials are stopped early due to overwhelming efficacy, it typically signals exceptional therapeutic value. The loss of clinical equipoise - meaning it became ethically unjustifiable to continue giving some patients placebo - is particularly noteworthy.
The commercial implications are substantial. WINREVAIR, already approved in 39 markets including the U.S., now has additional validation from the ZENITH trial's interim analysis. This strengthens its position in the $6 billion global PAH market. The drug's novel mechanism of action as an activin signaling inhibitor differentiates it from traditional vasodilator therapies, potentially positioning it as a new standard of care.
Three key factors make this development particularly impactful:
- Accelerated market adoption potential due to robust efficacy data across multiple trials
- Stronger positioning for favorable insurance coverage and reimbursement
- Enhanced competitive advantage against both existing treatments and pipeline candidates
The decision to transition HYPERION patients to the open-label SOTERIA extension study indicates confidence in long-term safety and efficacy. This additional real-world data will likely further strengthen WINREVAIR's market position and could support expanded indications in the future.
Robust evidence of the clinical benefit of WINREVAIR demonstrated in the STELLAR and ZENITH studies resulted in a loss of clinical equipoise in the HYPERION study
"After closely reviewing the robust efficacy data across a broad spectrum of patients evaluated in the WINREVAIR clinical development program, the steering committee has unanimously concluded that the HYPERION study, evaluating WINREVAIR versus placebo on top of background therapy, has lost clinical equipoise and should be stopped early,” said Dr. Vallerie McLaughlin**, Kim A Eagle MD Endowed Professor of Cardiovascular Medicine and Director, Pulmonary Hypertension Program, University of
“Based on the strong, positive interim efficacy data from the ZENITH trial, as well as the totality of available WINREVAIR data, we concluded that it would not be ethical to continue the HYPERION study,” said Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We are grateful to the dedicated community of patients who participated in these studies and are pleased to offer the option of receiving WINREVAIR through the Phase 3 SOTERIA open-label extension study.”
Findings from the HYPERION study will be available later this year and presented at a future medical congress.
WINREVAIR is currently approved in the
*World Health Organization
**Dr.
About HYPERION
The HYPERION study (NCT04811092) is a global, double-blind, placebo-controlled clinical trial to evaluate WINREVAIR when added to background PAH therapy in newly diagnosed intermediate or high-risk PAH patients. Participants enrolled in the study had a diagnosis within 12 months of study screening of symptomatic PAH (WHO Group 1, classified as FC II or III) and presentation of idiopathic or heritable PAH, PAH associated with connective tissue diseases (CTD), drug- or toxin-induced PAH, post shunt correction PAH, or PAH presenting at least one year following the correction of congenital heart defects.
The study enrolled approximately 300 study participants, who were randomized in a 1:1 ratio to either WINREVAIR plus background PAH therapy or placebo plus background PAH therapy. The primary composite outcome measure is time to clinical worsening (TTCW) as measured by first confirmed morbidity or mortality event. Clinical worsening events are defined as all-cause death, non-planned PAH worsening-related hospitalization of ≥ 24 hours, atrial septostomy, lung transplantation, and deterioration in six-minute walk test from baseline combined with at least one of the following changes including worsening of WHO FC from baseline, signs/symptoms of increased right heart failure, addition of a background PAH therapy or change in the background PAH therapy delivery route to parenteral.
Secondary outcome measures include improvement of six-minute walk distance (6MWD), improvement and maintenance or achievement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and improvement in WHO FC or maintenance of WHO FC II as well as additional measures. Participants in the HYPERION trial will have the opportunity to receive WINREVAIR as part of the open-label, long-term extension study, SOTERIA (NCT04796337), consistent with that study’s eligibility criteria.
About ZENITH
The ZENITH study (NCT04896008) is a global, double-blind, placebo-controlled clinical trial to evaluate WINREVAIR when added to maximum tolerated background PAH therapy on time to first event of all-cause death, lung transplantation, or PAH worsening related hospitalization of ≥24 hours, in participants with WHO FC III or IV PAH at high risk of mortality. ZENITH study inclusion criteria required Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 risk score of ≥9.
The study enrolled 172 participants, who were randomized in a 1:1 ratio to either WINREVAIR plus background PAH therapy or placebo plus background PAH therapy. The primary composite outcome measure is time to first confirmed morbidity or mortality event. Events are defined as all-cause death, lung transplantation, or PAH worsening-related hospitalization of ≥24 hours. Secondary outcome measures include overall survival, transplant-free survival and several additional measures. Participants who have completed the ZENITH trial have the opportunity to receive sotatercept as part of the open-label, long-term extension study, SOTERIA (NCT04796337), consistent with that study’s eligibility criteria.
About STELLAR
STELLAR (NCT04576988) is a pivotal Phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study designed to evaluate the safety and efficacy of WINREVAIR compared to placebo, as an add-on to background therapy for the treatment of adults with PAH (WHO Group 1). The primary endpoint was exercise capacity, as measured by 6MWD 24 weeks following initiation of treatment. Nine secondary outcome measures were assessed: proportion of participants achieving multicomponent improvement (consisting of improvement in 6MWD, improvement in NT-proBNP level, and either improvement in WHO FC or maintenance of WHO FC II); change from baseline in pulmonary vascular resistance (PVR); change from baseline in NT-proBNP levels; proportion of participants who improved in WHO FC; time to death or the first occurrence of a TTCW event; proportion of participants who maintained or achieved a low risk score using the simplified French Risk score calculator; change from baseline in the Physical Impacts domain score of PAH-SYMPACT®; change from baseline in the Cardiopulmonary Symptoms domain score of PAH-SYMPACT; and change from baseline in the Cognitive/Emotional Impacts domain score of PAH-SYMPACT.
About SOTERIA
SOTERIA (NCT04796337) is an ongoing open-label extension study evaluating the long-term safety, tolerability and efficacy of WINREVAIR when added to background therapy for the treatment of PAH in patients who have completed previous WINREVAIR studies without early discontinuation. The primary objective of SOTERIA is to evaluate long-term safety and tolerability. The secondary objective is to assess the continued efficacy of WINREVAIR, as measured by 6MWD, NT-proBNP, WHO FC, pulmonary vascular resistance, overall survival, and simplified French risk score. Results from the SOTERIA study were presented at the European Respiratory Society (ERS) International Congress in 2023.
About WINREVAIR™ (sotatercept-csrk) for injection, for subcutaneous use, 45 mg, 60 mg
WINREVAIR is FDA-approved 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. 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 in the
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
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 (≥
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 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
About Merck
At Merck, known as MSD outside of
Forward-Looking Statement of Merck & Co., Inc.,
This news release of Merck & Co., Inc.,
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 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.
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FAQ
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