Merck's WINREVAIR™ (sotatercept-csrk) has demonstrated a statistically significant and clinically meaningful reduction in the risk of morbidity or mortality events in adults with pulmonary arterial hypertension (PAH) in the Phase 3 ZENITH trial. The study, evaluating WINREVAIR in patients with WHO FC III or IV PAH at high risk of mortality, met its primary endpoint of time to first morbidity or mortality event (all-cause death, lung transplantation, or PAH worsening related hospitalization of ≥ 24 hours).
Based on these results, an independent data monitoring committee recommended that the ZENITH trial be stopped early, and all participants will be offered the opportunity to receive WINREVAIR through the SOTERIA open-label extension study. Preliminary assessments indicated that adverse events and serious adverse events were balanced between the treatment groups.
Clinical Impact of WINREVAIR
"PAH is a serious, progressive disease with a high incidence of morbidity and mortality," said Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. "Based on the primary endpoint demonstrating overwhelming efficacy, all ZENITH study participants will be offered the opportunity to receive WINREVAIR. These findings are impressive and support the potential of WINREVAIR to be practice-changing in the management of PAH."
The ZENITH trial enrolled 172 participants with WHO FC III or IV PAH at high risk of mortality, indicated by a REVEAL Lite 2.0 risk score of ≥9. Participants were randomized 1:1 to receive either WINREVAIR plus background PAH therapy or placebo plus background PAH therapy. The primary outcome was time to first confirmed morbidity or mortality event, defined as all-cause death, lung transplantation, or PAH worsening-related hospitalization of ≥ 24 hours. Secondary outcomes included overall survival and transplant-free survival.
Mechanism of Action
WINREVAIR is the first activin signaling inhibitor therapy approved for PAH. It works by improving the balance between pro-proliferative and anti-proliferative signaling to modulate vascular proliferation. Preclinical models have shown that WINREVAIR induces cellular changes associated with thinner vessel walls, partial reversal of right ventricular remodeling, and improved hemodynamics.
Current Status and Future Plans
WINREVAIR is currently approved in the U.S. and 36 countries based on results from the Phase 3 STELLAR trial. In November, it was submitted for approval in Japan based on the STELLAR trial and results from an open-label Phase 3 study in Japanese patients. Full results from ZENITH will be presented at an upcoming medical meeting and submitted to regulatory authorities.
About Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a rare, progressive, and life-threatening disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation. Approximately 40,000 people in the U.S. are living with PAH. The five-year mortality rate for patients with PAH is approximately 43%.
