- Phase 2 CADENCE (NCT04945460) presented Mar 29, 2026: 164 patients randomized 1:1:1 to placebo, 0.3 mg/kg and 0.7 mg/kg WINREVAIR Q3W; 0.7-mg/kg arm started at 0.3 mg/kg for three doses then escalated.
- Week-24 efficacy: PVR reduction vs placebo 1.02 WU (0.3 mg/kg, p=0.004) and 0.75 WU (0.7 mg/kg, p=0.024); mPAP −9.2 mmHg both doses; 6MWD +20.3 m (0.3 mg/kg) and +5.8 m (0.7 mg/kg).
- Safety and regulatory: SAEs 20% (0.3 mg/kg), 33% (0.7 mg/kg), 22% (placebo); bleeding ~26–27% on active vs 24% placebo; WINREVAIR (sotatercept-csrk) is FDA-approved for PAH and is subject of a licensing agreement with Bristol Myers Squibb.
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.
