The lack of a dose-response effect could be due to the high number of dropouts in the higher-dose Winrevair arm and the relatively small study population, a discussant for Merck explained.
Merck’s hypertension drug significantly improved heart function in a mid-stage study of a rare type of heart failure, paving the path forward to Phase 3 development—even as some analysts flagged potential concerns with the lack of a dose-response effect.
The latest data, presented Sunday at the 2026 Annual Scientific Session and Expo of the American College of Cardiology (ACC), validate the clinical benefits of Winrevair in patients with combined post- and precapillary pulmonary hypertension (CpcPH) due to heart failure with preserved ejection fraction (HFpEF), BMO Capital Markets told investors in a note the same day.
“But the lack of a clear dose response could raise some questions for investors,” the analysts cautioned.
In the Phase 2 CADENCE study, Merck compared two doses of Winrevair (0.3 mg/kg and 0.7 mg/kg) against placebo in more than 160 patients with CpcPH-HFpEF. Both doses elicited a significant reduction in pulmonary vascular resistance, a measure of how much work the heart has to do to pump blood through the lungs.
Winrevair’s lower dose appeared to have a stronger effect than its higher dose, however—the lack of dose-response effect that BMO flagged. During its presentation at ACC, a discussant for Merck attributed this result to the relatively small study population and the higher number of discontinuations and dose suspensions in the 0.7-mg/kg group.
“We are comfortable with this explanation,” the BMO analysts said, however admitting that some investor concerns could carry over into Winrevair’s late-stage program in this indication.
Guggenheim Partners was similarly optimistic about Merck’s data, with analysts writing early on Monday that “we are encouraged by the potential for Winrevair in this new population.” The firm’s key opinion leaders were “overwhelmingly positive” on the CADENCE data and the potential for Winrevair to expand into CpcPH-HFpEF, highlighting the unaddressed need in the market.
If approved for this indication, Winrevair could double its commercial opportunity, Guggenheim added.
Aside from hitting its primary endpoint, Winrevair also improved outcomes on the 6-minute walk distance test, a measure of functional performance, though the effect fell short of statistical significance.
Because CADENCE was designed to test secondary endpoints on a hierarchical basis, Merck wasn’t able to conduct formal statistical analyses on other outcomes. The pharma nevertheless reported numerical improvements in the time before a first clinical worsening event occurred and levels of NT-proBNP, a key disease biomarker.
With these data, Merck on Sunday doubled down on its plans to advance Winrevair into pivotal development for CpcPH-HFpEF. “CADENCE results support that the 0.3 mg/kg dose may optimize the benefit-risk profile of Winrevair” in this patient population, Mahesh Patel, vice president of global clinical development, said in a prepared statement. The pharma did not provide a timeline for its late-stage program.
Winrevair, approved for pulmonary arterial hypertension (PAH) in March 2024, is a fusion protein therapeutic that disrupts activin signaling, in turn preventing the thickening of blood vessel walls. 2025 turned out to be a good year for the product. In April 2025, data from the Phase 3 ZENITH trial showed that in certain PAH patients with a rare form of the disease, Winrevair cut the risk of major morbidity and mortality by 76% versus placebo. ZENITH led to a label expansion for Winrevair in October last year. 2025 sales of Winrevair hit $1.4 billion.
