Pooled trial analysis supports Winrevair as PAH treatment
Approved therapy safe, effective for patients when added to standard of care
Winrevair (sotatercept) is generally safe and effective for people with pulmonary arterial hypertension (PAH) when given in addition to their standard of care treatment, a pooled analysis of two clinical trials shows.
Along with other benefits, the clinical studies — the Phase 2 PULSAR trial (NCT03496207) and the Phase 3 STELLAR trial ( NCT04576988) — demonstrated that the approved PAH treatment effectively improved exercise capacity and reduced the risk of clinical worsening events for patients versus a placebo.
“This pooled analysis confirms that [Winrevair] delivers therapeutic benefit across a range of efficacy endpoints and has [favorable] safety,” the researchers wrote. “These results strengthen the existing evidence base to enable more informed clinical decisions that may lead to [optimized] therapeutic strategies in patients with PAH.”
The study, “Efficacy and safety of the activin signalling inhibitor, sotatercept, in a pooled analysis of PULSAR and STELLAR studies,” was published in the European Respiratory Journal. Winrevair is sold by Merck; several study authors are or were employees at Merck Sharp & Dohme, a subsidiary of Merck. The study was funded by Acceleron Pharma, also a
Merck subsidiary.
Researchers analyzed data from PULSAR and STELLAR trials
PAH is characterized by the narrowing of the pulmonary arteries, which are the blood vessels that carry blood through the lungs. Such narrowing is associated with excessive growth of the cells that line the inside of blood vessels, called endothelial cells.
Winrevair works to reduce the abnormal growth of these cells. Specifically, the active agent in Winrevair is designed to act as a trap for molecules belonging to the transforming growth factor beta (TGF-beta) superfamily of molecules that plays a central role in driving the abnormal growth of endothelial cells in PAH.
In this analysis, the researchers combined data from the PULSAR and STELLAR trials to assess Winrevair’s safety and efficacy in a larger number of PAH patients. Overall, the studies enrolled 429 patients, who were randomly selected to receive Winrevair (237 patients) or a placebo (192 patients). Treatment was given once every three weeks for six months.
“Pooling the results across these two studies offered a robust framework for undertaking the current post-hoc analysis allowing for evaluation of the efficacy and safety of [Winrevair] across a broader population,” the scientists wrote, noting that PULSAR and STELLAR had a similar design and duration.
Also, the team noted, “both studies enrolled similar populations of patients with group 1 PAH [classification] and similar disease characteristics, who were on similar approved background PAH therapies.”
The mean age of the participants was just younger than 48, and most were female and white individuals. The time since disease diagnosis was an average of 8.5 years, and slightly more than half of the patients (58.3%) had idiopathic disease, meaning of unknown origin.
At baseline, or the study’s start, 60% of patients were on triple therapy, used to target multiple disease pathways. Nearly 40% were on PAH treatment with prostacyclin infusions, which prompts blood vessels to widen. About one-third of the patients were receiving two medications.
Significant benefits seen for PAH patients with Winrevair add-on treatment
As seen in the two trials separately, adding Winrevair to background therapy significantly improved patients’ exercise capacity at 24 weeks, or nearly six months. Patients saw an increase in six-minute walking distance (6MWD) by a median of 38.4 meters (126 feet), compared with 5.3 meters (17.4 feet) with the placebo. Unlike the placebo, the treatment also reduced pulmonary vascular resistance, a measure of the resistance to blood flow, and the blood levels of NT-proBNP, a biomarker for heart failure.
Significantly more Winrevair-treated patients improved their World Health Organization (WHO) functional class than those on the placebo (27% vs.13.6%), and also achieved a multicomponent improvement (42.4% vs. 11%). This measure was defined as showing improvements relative to baseline in 6MWD, NT-proBNP, and improved or maintained WHO functional class.
Participants treated with Winrevair also had fewer events related to clinical worsening than those receiving the placebo (10 vs. 47 events), as well as a delay in time before disease worsening. This represented a relative risk reduction of 84% with Winrevair, the analysis found.
The results of this pooled analysis confirm [Winrevair] delivers therapeutic benefit across a range of efficacy endpoints, including exercise capacity… and has a [favorable] safety profile in patients with PAH on background standard-of-care therapy.
Clinical worsening included outcomes such as the need to start rescue therapy or increase the dose of the infusion prostacyclin by at least 10%, as well as PAH-related hospitalization, and worsening of PAH relative to baseline. Time to clinical worsening was assessed up to week 24 in PULSAR and up to week 78, or about 1.5 years, in STELLAR. Patients also experienced a significant reduction in both pulmonary and right heart pressures, among other cardiac benefits.
The frequency of treatment-emergent adverse events appearing or worsening after the start of treatment was similar between Winrevair and the placebo (85.2% vs. 88%). Adverse events related to treatment were more frequent in Winrevair-treated patients (43.9% vs. 26%). In contrast, the number of participants with severe events (14.8% vs. 20.3%) and those leading to death (0.4% vs. 3.1%) was lower in the Winrevair group.
Overall, according to the researchers, “the results of this pooled analysis confirm [Winrevair] delivers therapeutic benefit across a range of efficacy endpoints, including exercise capacity… and has a [favorable] safety profile in patients with PAH on background standard-of-care therapy.”
The team called for additional trials testing the PAH treatment over the long term, and noted that an ongoing Phase 3 study called SOTERIA (NCT04796337) is assessing Winrevair’s safety and efficacy.
About the Author
