Merck’s Winrevair Slashes Morbidity and Mortality Risk in Pulmonary Arterial Hypertension

Winrevair reduced the risk of major morbidity and mortality events by 76% compared to placebo in the Phase III ZENITH trial1 3.

The primary endpoint was a composite of all-cause death, lung transplantation, and PAH worsening-related hospitalization1 3.

17.4% of patients treated with Winrevair experienced major morbidity and mortality events, compared to 54.7% in the placebo group1 3.

Winrevair is the first FDA-approved activin signaling inhibitor therapy for PAH4 9.

The ZENITH trial was stopped early due to overwhelming efficacy, following recommendations from an independent data monitoring committee2 4.

Study Details

The Phase III ZENITH trial evaluated Winrevair (sotatercept-csrk) in adults with pulmonary arterial hypertension (PAH) WHO functional class III or IV at high risk of mortality1. Patients were on maximum tolerated background PAH therapy1.

Efficacy Results

At a median follow-up of 10.6 months, Winrevair demonstrated significant benefits:

76% reduction in relative risk of major morbidity and mortality events1 3

Individual components of the primary endpoint:

Deaths:
8.1% (Winrevair) vs. 15.1% (placebo)1

Lung transplantation:
1.2% (Winrevair) vs. 7.0% (placebo)1

PAH-related hospitalizations:
9.0% (Winrevair) vs. 50.0% (placebo)1

Safety Profile

The safety profile of Winrevair was generally consistent with previous studies1:

No patients discontinued treatment due to adverse events1

Serious adverse events:
53.5% (Winrevair) vs. 64.0% (placebo)1

Treatment-related adverse events:
65.1% (Winrevair) vs. 32.6% (placebo)1

Bleeding events:
62.8% (Winrevair) vs. 34.9% (placebo), mostly non-serious1

Implications and Future Directions

Winrevair's impressive results in the ZENITH trial demonstrate its potential to significantly improve outcomes for PAH patients4. The drug's mechanism of action targets an underlying cause of PAH by modulating vascular proliferation9. Merck is continuing to build evidence for Winrevair, with the HYPERION study also ending early due to strong efficacy findings8.

These results support Winrevair's potential to be practice-changing in PAH management, offering new hope for patients with this severe and progressive disease4 6.