Merck reports Phase 2 CADENCE data for WINREVAIR in CpcPH-HFpEF

Merck announced detailed results from the Phase 2 CADENCE study of WINREVAIR™ (sotatercept-csrk) in adults with the syndrome of combined post- and precapillary pulmonary hypertension and heart failure with preserved ejection fraction (CpcPH-HFpEF). In this patient population, WINREVAIR met the primary endpoint of change in pulmonary vascular resistance and showed a statistically significant and clinically meaningful reduction from baseline in pulmonary vascular resistance versus placebo at week 24.

The study was designed to evaluate the efficacy, safety and tolerability of two doses, 0.3 mg/kg and 0.7 mg/kg. WINREVAIR showed a 1.02 Wood units reduction for the 0.3 mg/kg dose (n=54, 95% CI, -1.81, -0.23, p=0.004) and a 0.75 Wood units reduction for the 0.7 mg/kg dose (n=55, 95% CI, -1.52, 0.03, p=0.024) versus placebo (n=55) at week 24.

Important secondary endpoints explored included six-minute walk distance, echocardiographic measures, N-terminal pro-B-type natriuretic peptide levels and time to clinical worsening. Patients in the 0.7 mg/kg arm showed an increase of 5.8 meters in six-minute walk distance that did not reach statistical significance (95% CI, -17.3, 28.9). While subsequent secondary endpoints were not formally tested due to the prespecified hierarchical testing strategy, there was a 20.3-meter increase from baseline in six-minute walk distance in patients treated with WINREVAIR 0.3 mg/kg (95% CI, 1.5, 39.1).

Additional findings from the week 24 analysis compared with placebo included reductions in mean pulmonary arterial pressure of -9.19 for WINREVAIR 0.3 mg/kg (95% CI, -13.00, -5.38) and -9.22 for WINREVAIR 0.7 mg/kg (95% CI, -12.97, -5.46). The reduction in pulmonary arterial wedge pressure from baseline was -3.04 for WINREVAIR 0.3 mg/kg (95% CI, -5.77, -0.32) and -2.53 for WINREVAIR 0.7 mg/kg (95% CI, -5.33, 0.28).

The reduction in NT-proBNP levels from baseline was -344 pg/mL for WINREVAIR 0.3 mg/kg (95% CI, -656, -31) and -402 pg/mL for WINREVAIR 0.7 mg/kg (95% CI, -846, 42). Time to first occurrence of a clinical worsening event was prolonged with WINREVAIR 0.3 mg/kg (HR: 0.18 [95% CI, 0.05, 0.62]) and WINREVAIR 0.7 mg/kg (HR: 0.59 [95% CI, 0.25, 1.36]).

The safety profile observed in CpcPH-HFpEF was generally consistent with the known safety profile for WINREVAIR in pulmonary arterial hypertension. Merck said the totality of evidence and consistency in trends across multiple endpoints from the CADENCE study support advancement of WINREVAIR into a registrational Phase 3 program in CpcPH-HFpEF, and that the 0.3 mg/kg dose may optimize the benefit-risk profile in this population.

The late-breaking data were presented at the American College of Cardiology’s Annual Scientific Session and Expo and simultaneously published in Circulation. Merck said it is working with regulatory agencies to design a Phase 3 registrational study with endpoints that focus on clinical outcomes most relevant to the needs of this patient population.