Treatment with sotatercept, added to stable background therapy, significantly improves exercise capacity in people with pulmonary arterial hypertension (PAH), according to topline results from the phase 3 STELLAR trial, Merck has announced.  

Sotatercept is an investigational, potential first-in-class activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein designed to rebalance pro-proliferative (ActRIIA/Smad2/3-mediated) and anti-proliferative (BMPRII/Smad1/5/8-mediated) signaling associated with pulmonary arterial wall and right ventricular remodeling.

STELLAR tested the safety and efficacy of sotatercept (given at a starting dose of 0.3 mg/kg with a target dose of 0.7 mg/kg administered subcutaneously every 21 days) vs placebo added to standard background therapy in 324 adults with PAH (World Health Organization [WHO] Group 1).

Topline results show that the trial met its primary efficacy outcome measure, demonstrating a statistically significant and clinically meaningful improvement in 6-minute walk distance (6MWD) from baseline at 24 weeks, Merck said.

Eight of nine secondary efficacy outcome measures also achieved statistical significance.

These include the proportion of participants achieving multicomponent improvement, defined as improvement in 6MWD, N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and improvement in either WHO functional class (WHO FC) or maintenance of WHO FC II, and the outcome measure of time to death or the first occurrence of a clinical worsening event (TTCW).

The only secondary endpoint in which significant improvements were not detected was the cognitive/emotional impacts domain score of PAH-SYMPACT, a measure of disease impact.

The overall safety profile of sotatercept in STELLAR was generally consistent with what has been observed in phase 2 testing, the release notes. The company plans to present results from the study at an upcoming scientific meeting.

Sotatercept has been granted breakthrough therapy designation by the US Food and Drug Administration, as well as priority medicines designation by the European Medicines Agency for the treatment of PAH.

In a statement announcing the results, Dean Y. Li, MD, PhD, president, Merck Research Laboratories, said, “We believe that in totality, the results observed in the STELLAR study suggest that sotatercept has the potential to transform the treatment of patients with PAH. We are moving with urgency on our regulatory applications to bring this investigational therapy to these patients.”

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