Phase 3 STELLAR Trial Indicates Efficacy of Sotatercept for Pulmonary Arterial Hypertension

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Sotatercept added to background therapy demonstrated significant improvement in exercise capacity compared to placebo.

Today, positive top-line results were announced from the Phase 3 STELLAR trial evaluating the safety and efficacy of sotatercept for the treatment of pulmonary arterial hypertension (PAH).

The investigational activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein from Merck was evaluated as an add-on to stable background therapy for PAH treatment.

The trial met its primary efficacy outcome measure, with sotatercept demonstrating a statistically significant and clinically meaningful improvement in 6-minute walk distance (6MWD) from baseline at 24 weeks.

Additionally, eight of nine secondary efficacy outcome measures achieved statistical significance, including the outcome measure of proportion of participants achieving multicomponent improvement.

The study defined this as improvement in 6MWD, improvement in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and either improvement in WHO FC or maintenance of WHO FC II), as well as the outcome measure of time to death or first occurrence of a clinical worsening event.

“In the Phase 3 STELLAR study, sotatercept added to currently approved background therapy showed a profound effect on the primary efficacy outcome measure of improvement from baseline to 24 weeks in six-minute walk distance,” said Dean Y. Li, President, Merck Research Laboratories in an accompanying release. “The results from the secondary efficacy outcomes, including a favorable benefit seen in patients’ time to a clinical-worsening event, are especially noteworthy.”

The Cognitive/Emotional Impacts domain score of PAH-SYMPACT, assessed as the ninth secondary outcome measure, did not achieve statistical significance. The overall safety profile of sotatercept in the phase 3 trial was considered to be generally consistent with what was observed in the phase 2 trial.

The fusion protein was 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.

“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,” Li added. “We are moving with urgency on our regulatory applications to bring this investigational therapy to these patients.”

Sotatercept has been granted Breakthrough Therapy designation by the US Food and Drug Administration and Priority Medicines designation by the European Medicines Agency for the treatment of PAH.

PAH is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation.

An estimated 40,000 people in the US and 30,000 people in the European Union are living with PAH, with the rare disorder progressing rapidly for many patients despite current standard of care treatment. The disorder leads to significant strain on the heart and patients with PAH have a 5-year mortality rate of approximately 43 percent.