A Study of Sotatercept in Participants With PAH WHO FC III or FC IV at High Risk of Mortality (MK-7962-006/ZENITH)

Phase 3 Completed 173 enrolled Acceleron Pharma, Inc.

RandomizedParallel-groupTriple-blindTreatment

Summary

The objective of this study is to evaluate the effects of sotatercept (MK-7962, formerly called ACE-011) treatment (plus maximum tolerated background pulmonary arterial hypertension \[PAH\] therapy) versus placebo (plus 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 World Health Organization (WHO) functional class (FC) III or FC IV PAH at high risk of mortality.

Timeline

Start: 2021-12-01
Primary completion: 2024-07-26
Completion: 2025-02-18

Outcome

Met primary endpoint

paper At least one primary end-point event occurred in 15 patients (17.4%) in the sotatercept group and in 47 patients (54.7%) in the placebo group PMID 40167274 ↗

paper hazard ratio, 0.24; 95% confidence interval, 0.13 to 0.43; P<0.001 PMID 40167274 ↗

release “ZENITH met its primary endpoint of time to first morbidity or mortality event” merck.com ↗

release “ZENITH試験は、最初の疾患状態の悪化／死亡イベント（全死亡、肺移植、またはPAH悪化に関連する24時間以上の入院）が発現するまでの時間を検討した主要エンドポイントを達成しました。” msd.co.jp ↗

Publications

Results Humbert M, McLaughlin VV, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, Preston IR, Souza R, Waxman AB, Moles VM, Savale L, Vizza CD, Rosenkranz S, Shi Y, Miller B, Mackenzie HS, Kim SS, Loureiro MJ, Patel MJ, Koglin J, Cornell AG, Hoeper MM; ZENITH Trial Investigators. Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death. N Engl J Med. 2025 May 29;392(20):1987-2000. doi: 10.1056/NEJMoa2415160. Epub 2025 Mar 31.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Sotatercept	Protein / enzyme biologic	0.7 mg/kg	Subcutaneous