Two clinical trials of Merck’s pulmonary arterial hypertension (PAH) drug Winrevair were so conclusive that the studies were halted within the last year because the efficacy of the treatment was assured.
Tuesday, Merck reported results from the phase 3 Hyperion study, which showed that Winrevair, when combined with background therapy, achieved its primary endpoint by reducing the risk of clinical worsening events by 76% compared with placebo in recently diagnosed adults.
Of the patients on placebo, 37% experienced a clinically worsening event versus 11% on Winrevair. Worsening events were defined as all-cause death, unplanned PAH-related hospitalizations of greater than 24 hours, atrial septostomy, lung transplantation or PAH deterioration.
All of the 320 patients in the trial were on background therapy, with half receiving Winrevair and the other half taking placebo. The participants were diagnosed within the last year, with more than 70% on double background therapy.
The severity of disease for the patients was functional class (FC) II or III on a four-grade scale, as defined by the World Health Organization. The likelihood of disease progression for those in the study was classified as intermediate or high-risk.
The study also showed a benefit for patients as early as six weeks after receiving Winrevair, and there was a consistent treatment effect across all prespecified subgroups—including participants with idiopathic PAH, those with connective tissue disease and those taking double background therapy and triple background therapy. Winrevair’s effects were also consistent between those classified as intermediate or intermediate-to-low risk of disease progression.
“PAH is a rare condition that can progress quickly making diagnosis and early treatment critically important,” Vallerie McLaughlin, M.D., a professor at the University of Michigan, said in a release. “The patients with PAH enrolled in HYPERION were early in their treatment journey, had co-morbidities and were older, which reflects the type of patients we are diagnosing in a contemporary real-world setting.”
Results from the study were presented Tuesday at the European Respiratory Society Congress and were published in The New England Journal of Medicine.
The study also achieved two of its three secondary endpoints. While 29% of Winrevair patients met all three pre-specified standards for multicomponent improvement, 15% of those on placebo did the same.
Two of the secondary endpoints were determined through different mortality risk assessment tools. While Winrevair succeeded using one measurement tool, REVEAL LITE 2, it came up short of reaching statistical significance in the simplified French risk score.
The results add to the growing body of evidence of the effectiveness of Winrevair, which was approved in March 2024. Merck gained the first-in-class activin signaling inhibitor in its $11.5 billion acquisition of Acceleron Pharma in 2021.
In the Stellar trial, which set up the FDA’s green light, patients on Winrevair plus standard of care improved their exercise capacity by an average distance of 41 meters in a six-minute walk test. The study also showed that Winrevair provided statistically significant improvements in eight of nine secondary measures, including extending the time to a clinical worsening event.
In March of this year, Merck revealed data from the Zenith trial, which also was halted early and included 172 patients at the highest risk of mortality, those in the FC III or IV category. The study achieved its primary endpoint as Winrevair reduced the risk of clinical worsening events by 76% versus placebo, with both patient arms receiving maximum background therapy.
Merck is off to a successful launch of Winrevair, which is primed to achieve blockbuster sales this year. In the second quarter, it generated revenue of $336 million, which was up from $280 million in the previous period. After results from Zenith were revealed, analysts from Citi jacked up their 2030 sales estimate for Winrevair to a range of $5.7 billion to $6.1 billion.