Merck's Winrevair (sotatercept-csrk) has demonstrated significant efficacy in reducing the risk of all-cause death, lung transplant, or hospitalization in adults with advanced pulmonary arterial hypertension (PAH). The positive results from the Phase 3 ZENITH trial (NCT04896008) led to an early halt of the study based on the recommendation of an independent data monitoring committee.
The ZENITH trial enrolled 172 adults with advanced PAH in WHO functional class 3 or 4, all considered to be at a high risk of dying. Participants received Winrevair (starting dose of 0.3 mg/kg, target dose of 0.7 mg/kg) or a placebo injection every three weeks, in addition to standard PAH treatments. The primary endpoint was the time to a confirmed morbidity or mortality event, defined as death from any cause, lung transplant, or hospitalization due to PAH complications lasting at least one day. Secondary measures included overall survival, transplant-free survival, and clinical tests of disease severity.
Key Findings from the ZENITH Trial
Top-line data revealed that Winrevair achieved a statistically significant and clinically meaningful reduction in the risk of morbidity or mortality events compared to the placebo. Adverse events were reported to be balanced between the two groups in an early assessment. Due to these compelling results, all ZENITH participants are now being offered the opportunity to continue or start Winrevair treatment as part of the SOTERIA extension study (NCT04796337).
"Based on the primary endpoint demonstrating overwhelming efficacy, all ZENITH study participants will be offered the opportunity to receive Winrevair," said Eliav Barr, MD, senior vice president and head of global clinical development at Merck Research Laboratories.
Mechanism of Action and Prior Approvals
Winrevair's active ingredient is an activin signaling inhibitor, designed to block the activity of proteins implicated in the uncontrolled growth of endothelial cells lining the pulmonary arteries. It is administered via subcutaneous injection once every three weeks. Winrevair has already received approval in the U.S., Canada, and the European Union for treating adults with PAH, generally for those in WHO functional class 2 or 3.
Ongoing Research
In addition to the ZENITH trial, Winrevair is being investigated in other clinical trials. The Phase 3 HYPERION trial (NCT04811092) is evaluating Winrevair in adults newly or recently diagnosed with PAH in WHO functional class 2 or 3 who are at intermediate or high risk of disease progression. The Phase 2 MOONBEAM trial (NCT05587712) is assessing the therapy's safety and tolerability in children and adolescents (ages 1-17) with PAH.
"These findings are impressive, set a high evidentiary bar for studies of future candidates developed for the treatment of PAH and support the potential of Winrevair to be practice-changing in the management of PAH," Barr added. Detailed results from the ZENITH trial will be submitted to regulatory authorities and presented at a future medical meeting.
