November 18, 2025 — Leads & Copy —
Merck (NYSE: MRK) announced positive topline results from its Phase 2 CADENCE study, which evaluated WINREVAIR™ (sotatercept-csrk) for the treatment of combined post- and precapillary pulmonary hypertension (CpcPH) in adults. The condition is caused by heart failure with preserved ejection fraction (HFpEF).
The CADENCE study met its primary endpoint, demonstrating a statistically significant and clinically meaningful reduction in pulmonary vascular resistance (PVR) from baseline at 24 weeks compared to a placebo. According to a preliminary assessment, the safety profile observed in the CADENCE study was consistent with the known safety profile for WINREVAIR.
Dr. Mahesh Patel, vice president, global clinical development, Merck Research Laboratories, said that WINREVAIR improved pulmonary vascular resistance in the study. Patel described pulmonary vascular resistance as an important hemodynamic measurement related to cardiac and pulmonary blood vessel function. He said that it has the potential to translate into improved outcomes for patients with CpcPH due to HFpEF.
The CADENCE trial, according to Patel, was designed as a proof-of-concept study to evaluate the pharmacological activity of WINREVAIR in a new patient population, with the goal of informing further Phase 3 development.
The company plans to present these results at a future scientific congress and intends to move forward with Phase 3 development.
WINREVAIR has been approved by the U.S. Food and Drug Administration (FDA) as an activin signaling inhibitor for the treatment of adults with pulmonary arterial hypertension (PAH, WHO* Group 1 pulmonary hypertension). It is used to improve exercise capacity and WHO functional class (FC) and reduce the risk of clinical worsening events, including hospitalization for PAH, lung transplantation, and death. It is currently approved in more than 50 countries.
CADENCE is a randomized, double-blind, placebo-controlled Phase 2 proof-of-concept study (NCT04945460) evaluating the efficacy and safety of WINREVAIR versus placebo in adults with CpcPH due to HFpEF. Patients in the trial had a diagnosis of CpcPH due to HFpEF with New York Heart Association (NYHA) FC II or III. CADENCE was designed as a proof-of-concept study with biomarkers, invasive hemodynamics, non-invasive imaging, and exercise capacity. The primary endpoint is change from baseline in PVR. The study further assessed exercise capacity, echocardiographic endpoints, biomarker endpoints, and clinical endpoints.
The study enrolled 164 participants, who were randomized in a 1:1:1 ratio to one of the three treatment groups (placebo, 0.3mg/kg WINREVAIR and 0.7mg/kg WINREVAIR) during the placebo-controlled treatment period.
CpcPH represents a subset of pulmonary hypertension due to left heart disease (PH-LHD), also known as Group 2 pulmonary hypertension. CpcPH is associated with poorer outcomes compared to other types of Group 2 PH. It is harder to treat because it involves both advanced left-sided heart disease and progressive remodeling of the pulmonary vasculature. There are no treatments specifically approved for CpcPH today. CpcPH due to HFpEF is believed to be a rare, though potentially underdiagnosed condition.
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.
WINREVAIR may increase hemoglobin (Hgb), decrease platelet count, cause fetal harm when administered to a pregnant woman, and impair female and male 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.
Dr. Mahesh Patel, vice president, global clinical development, Merck Research Laboratories.
Source: Merck
