Merck: WINREVAIR Phase 2 CADENCE shows proof‑of‑concept in CpcPH‑HFpEF

Study overview

CADENCE (NCT04945460) is a double-blind, randomized, placebo-controlled Phase 2 proof-of-concept trial in adults with combined post- and precapillary pulmonary hypertension and HFpEF (CpcPH-HFpEF); 164 participants were randomized 1:1:1 to placebo, WINREVAIR 0.3 mg/kg Q3W or WINREVAIR 0.7 mg/kg Q3W (0.7‑mg/kg arm started at 0.3 mg/kg for three doses then escalated); data presented at ACC.26 and published in Circulation (Mar 29, 2026).

Primary and key hemodynamic outcomes

At week 24 the primary endpoint, change in pulmonary vascular resistance (PVR), showed reductions versus placebo of 1.02 Wood units for 0.3 mg/kg (95% CI −1.81, −0.23; p=0.004) and 0.75 WU for 0.7 mg/kg (95% CI −1.52, 0.03; p=0.024); mean pulmonary arterial pressure fell ≈9.2 mmHg with both doses and pulmonary arterial wedge pressure fell −3.04 mmHg (0.3 mg/kg) and −2.53 mmHg (0.7 mg/kg).

Functional and biomarker findings

Six-minute walk distance increased 20.3 m for 0.3 mg/kg (95% CI 1.5, 39.1) and 5.8 m for 0.7 mg/kg (95% CI −17.3, 28.9; not statistically significant); NT-proBNP fell −344 pg/mL (0.3 mg/kg) and −402 pg/mL (0.7 mg/kg); time to first clinical worsening was prolonged (HR 0.18 for 0.3 mg/kg; HR 0.59 for 0.7 mg/kg).

Safety

Serious adverse events occurred in 20% (0.3 mg/kg), 33% (0.7 mg/kg) and 22% (placebo); bleeding events were 26%, 27% and 24% respectively; adverse events leading to death occurred in one patient (0.7 mg/kg) and two patients (placebo); discontinuations were observed only in the 0.7 mg/kg arm.

Next steps

Merck reports the totality of evidence supports advancing WINREVAIR (sotatercept‑csrk) into a registrational Phase 3 program and indicates the 0.3 mg/kg dose may optimize benefit–risk; regulatory discussions are underway.