Merck Shares Positive Phase III Data from Pulmonary Arterial Hypertension Trial

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Merck has announced positive results from its Phase III clinical trial evaluating WINREVAIR (sotatercept-csrk) in adults with pulmonary arterial hypertension (PAH) functional class (FC) III or IV at high risk of mortality. The ZENITH study (NCT04896008) met its primary endpoint with WINREVAIR demonstrating a statistically significant and clinically meaningful reduction in the risk of morbidity or mortality events compared to placebo.¹

According to Merck, an independent data monitoring committee recommended ZENITH be stopped early based on these positive results. Participants will be offered the opportunity to receive WINREVAIR through the SOTERIA open-label extension study.

In a press release, Eliav Barr, MD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories said, “PAH is a serious, progressive disease with a high incidence of morbidity and mortality. Based on the primary endpoint demonstrating overwhelming efficacy, all ZENITH study participants will be offered the opportunity to receive WINREVAIR. 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.”

ZENITH is a global, double-blind, placebo-controlled trial evaluating WINREVAIR when added to maximum tolerated background PAH therapy on time to first event of all-cause death, lung transplantation, or PAH worsening related hospitalization of ≥ 24 hours. Outside of the primary endpoint, secondary outcome measures include overall survival and transplant-free survival. The study enrolled 172 participants who were randomized 1:1 to receive either WINREVAIR or placebo.

“The ZENITH trial was designed to evaluate whether the addition of WINREVAIR, an activin signaling inhibitor, could reduce the risk of death, lung transplantation, or PAH hospitalizations for patients living with advanced PAH,” Vallerie McLaughlin, MD, Kim A Eagle MD endowed professor of cardiovascular medicine and director, Pulmonary Hypertension Program, University of Michigan in Ann Arbor, said in a press release. “This is the first study in PAH in which the interim analysis led to an early conclusion of the study due to overwhelming efficacy. WINREVAIR has brought significant optimism to the field, and we thank the investigators and patients for being part of this important study.”

In March, the FDA approved WINREVAIR for the treatment of adults with PAH to increase exercise capacity, improve FC, and reduce the risk of clinical worsening events. The approval is based on results from the STELLAR trial (NCT04576988), in which WINREVAIR demonstrated an increase in six-minute walk distance.²

Pulmonary arterial hypertension is a rare, progressive and ultimately life-threatening disease in which blood vessels in the lungs thicken and narrow, causing significant strain on the heart,” Marc Humbert, MD, PhD, professor of medicine and director of the Pulmonary Hypertension Reference Center at the Université Paris-Saclay and investigator on the Phase III STELLAR study, said in an earlier press release. “Based on the Phase III STELLAR trial, adding WINREVAIR to background PAH therapy demonstrated significant clinical benefits compared to background PAH therapy alone. This approval is an important milestone, as it offers healthcare providers a novel therapeutic option that targets a new PAH treatment pathway.”

References

1. Merck Announces Pivotal Phase 3 ZENITH Trial Evaluating WINREVAIR™ (sotatercept-csrk) Met Primary Endpoint at Interim Analysis. News release. Merck. November 25, 2024. Accessed November 27, 2024. https://www.merck.com/news/merck-announces-pivotal-phase-3-zenith-trial-evaluating-winrevair-sotatercept-csrk-met-primary-endpoint-at-interim-analysis/

2. FDA Approves Merck’s WINREVAIR™ (sotatercept-csrk), a First-in-Class Treatment for Adults with Pulmonary Arterial Hypertension (PAH, WHO* Group 1). News release. Merck. March 26, 2024. Accessed November 27, 2024. https://www.merck.com/news/fda-approves-mercks-winrevair-sotatercept-csrk-a-first-in-class-treatment-for-adults-with-pulmonary-arterial-hypertension-pah-who-group-1/