Winrevair reduces risk of death, transplant, hospitalization in trial
ZENITH study ended early so those on placebo could switch to the therapy
Treatment with the approved therapy Winrevair (sotatercept-csrk) significantly reduced the risk of death, lung transplant, or hospitalization in people with pulmonary arterial hypertension (PAH), according to results from the Phase 3 ZENITH clinical trial.
Findings were published in The New England Journal of Medicine, in the study, “Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death.” The results were simultaneously presented at the American College of Cardiology’s Annual Scientific Session and Expo. The work was funded by Merck, the company that sells Winrevair.
“These data support the practice-changing potential of Winrevair for a broad range of patients with PAH,” Marc Humbert, MD, PhD, co-author of the study at Université Paris-Saclay, said in a press release from Merck.
The results from the ZENITH study were so positive the placebo-controlled trial ended early so all patients could switch to receiving Winrevair at the recommendation of an independent data monitoring committee. Another trial testing Winrevair against a placebo in people with recently diagnosed PAH was also ended early so all patients could receive active treatment.
“The impressive results from ZENITH demonstrated that patients on Winrevair had a 76 percent risk reduction in the composite of all-cause death, lung transplantation and hospitalization for PAH compared to placebo, with improvement observed early in treatment and increasing benefit throughout the study,” said Eliav Barr, MD, chief medical officer, senior vice president and head of global clinical development at Merck Research Laboratories. “These results led to the ZENITH study being the first PAH clinical trial stopped early due to overwhelming efficacy, representing an important milestone in clinical research with promise for the PAH community.”
Winrevair reduces abnormal growth of blood vessel cells
Winrevair was approved last year to treat adults with PAH in the U.S. as well as the European Union. The therapy is given by subcutaneous (under-the-skin) injection every three weeks, and it is designed to reduce the abnormal growth of blood vessel cells that contributes to disease progression in PAH.
The ZENITH clinical trial (NCT04896008) enrolled 172 people with PAH who, based on standardized metrics, were judged to be at high risk of dying within one year despite available treatments. Most participants were white and female. The patients were randomly assigned to receive Winrevair or a placebo, given on top of standard therapies.
The study’s main goal was to assess whether Winrevair was better than the placebo at preventing patients from reaching a composite endpoint that included death, lung transplant, and/or being hospitalized due to worsening PAH for at least 24 hours.
Results showed the study met this goal: fewer than 1 in 5 (17.4%) patients on Winrevair experienced one of these adverse outcomes compared with more than half (54.7%) of patients on the placebo. Statistically, this works out to a 76% lower likelihood of adverse outcomes in patients given Winrevair.
“The ZENITH study represents the first PAH clinical trial with a primary endpoint comprised entirely of major outcome measures – all-cause death, lung transplantation and hospitalization for PAH,” Humbert said. “Winrevair had a significant and clinically meaningful impact on the composite of these outcomes.”
Looking at each outcome individually also indicated favorable effects of Winrevair. Patients given the therapy had lower rates of death (8.1% vs. 15.1%), transplant (1.2% vs. 7%), and PAH-related hospitalizations (9.3% vs. 50%). These differences weren’t all statistically significant, though the researchers stressed that since the trial was ended early there’s a lower likelihood of finding statistically meaningful results on these secondary endpoints because there wasn’t much data available to analyze.
Side effects include nosebleeds, damaged veins beneath the skin, low platelet count
The most common treatment-related safety issues seen in ZENITH included known side effects of Winrevair such as nosebleeds, bleeding from the gums, damaged veins visible beneath the skin (known as telangiectasias or spider veins), high counts of hemoglobin (the protein that carried oxygen in red blood cells), and low counts of platelets. Vomiting and back pain were also more common in patients given Winrevair than those given the placebo. Overall, “the safety profile was generally consistent with that seen in previous trials,” the researchers wrote.
After the ZENITH study ended, the participants had the option to continue into an open-label extension study called SOTERIA (NCT04796337) where all are being treated with Winrevair and monitored for long-term outcomes. Data from this study will help characterize the long-term safety profile of the therapy, researchers noted.
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