Luspatercept-AAMT

New data unveiled Monday showed that Merck’s Winrevair can significantly cut the risk of death, lung transplantation and hospitalization in patients with a rare form of high blood pressure in the lungs, potentially providing a boost to sales. The data come from a study that was stopped early for overwhelming efficacy in November . However, this early halt meant that a secondary endpoint looking at deaths alone faced a higher bar and did not meet statistical significance. It is now unclear whether Winrevair, which was approved for pulmonary arterial hypertension (PAH) around a year ago , will be able to get a specific mortality claim on its label as the company had previously hoped. What is clear is that the trial, named ZENITH, scored a huge success on its primary endpoint. Winrevair, an injected activin receptor fusion protein, reduced a composite of all-cause death, lung transplantation and hospitalization for PAH by 76% compared with placebo. Of those given Merck’s drug, 17.4% experienced one or more of these major morbidity and mortality events, versus 54.7% of those given placebo. ZENITH enrolled 172 adults with advanced PAH who were at high risk of mortality and were on maximum tolerated background therapy. This finding, presented at the American College of Cardiology’s Annual Scientific Sessions, is important because Winrevair’s approval was based on softer endpoints, including improving patients’ exercise capacity and symptoms. Evidence of a more concrete effect on patients’ health could extend the drug’s reach. “Four to five weeks after initiation of [Winrevair] there’s already a detectable difference in deaths, hospitalization and lung transplant between both groups,” Joerg Koglin, senior VP of global clinical development at Merck, told Endpoints News . “That’s an endpoint that was never tackled by any other PAH drug development program,” he added. However, the crucial secondary endpoint of overall survival was not met. There were seven deaths in the Winrevair arm compared with 13 in the placebo arm, but the statistical threshold here was set at a p-value of 0.0021, a harder bar to hit than the more usual 0.05. Koglin said that this tougher standard was a statistical necessity when interim analyses are used. The actual p-value for mortality at the interim point was 0.0313. “If we would’ve seen that p-value at the end of the study, of course that would’ve been significant,” he said. When examined individually, the other components of the composite endpoint also favored Merck’s drug, though again the company was unable to claim statistical significance. One Winrevair patient had a lung transplant compared with six in the placebo arm, and eight patients in the drug group were hospitalized for PAH versus 43 — half the patients — in the placebo group. Safety was consistent with earlier studies, such as the STELLAR trial which led to Winrevair’s approval. The group will submit the ZENITH data to the FDA and other agencies, and Koglin said that “one of the discussions with regulators would be if the survival benefit should be spelled out more clearly in the label.” Whether a mortality benefit is added to the label or not, sales could see an uptick. With Winrevair, Koglin said, “you see an impact on hard endpoints and there is no other program out there that ever has shown a similar effect. It will be a strong argument for a physician to consider [Winrevair] for a given patient.” Merck confirmed that it does not anticipate a price increase for Winrevair even if the drug does receive a label update. Winrevair was one of the two main products behind Merck’s $11.5 billion acquisition of Acceleron in 2021 . The drug had sales of $419 million last year. The other main reason for the Acceleron deal was the blood disorder therapy Reblozyl, which sold $371 million in 2024. Winrevair sales will have to grow if Merck is to make its money back.