Merck Reports Positive Top-line Results from Phase 3 Trial of Sotatercept for Adults with PAH

Merck reported positive top-line results from the pivotal phase 3 STELLAR trial evaluating the safety and efficacy of sotatercept, which demonstrated significant improvement in exercise capacity and key secondary outcome measures as an add-on to stable background therapy for the treatment of pulmonary arterial hypertension.

Photo: Dean Li, president, Merck Research Laboratories

Pulmonary arterial hypertension (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. Currently, an estimated 40,000 people in the United States and 30,000 people in the European Union are living with PAH and the disease progresses rapidly for many patients despite current standard of care treatment. PAH results in significant strain on the heart, leading to limited physical activity, heart failure and reduced life expectancy. The 5-year mortality rate for patients with PAH is approximately 43 percent.

Sotatercept is an experimental, potential first-in-class activin receptor type IIA-Fc fusion protein in development for the treatment of adult patients with pulmonary arterial hypertension. Sotatercept was designed to rebalance pro-proliferative and anti- proliferative signaling associated with pulmonary arterial wall and right ventricular remodeling.

The U.S. Food and Drug Administration has granted Breakthrough Therapy designation to sotatercept and the European Medicines Agency granted it Priority Medicines designation for the treatment of PAH.

Merck acquired exclusive rights to sotatercept in the pulmonary hypertension field through the acquisition of Acceleron Pharma. Sotatercept is the subject of a licensing agreement with Bristol Myers Squibb.

The trial met its primary efficacy outcome measure, demonstrating a statistically significant and clinically meaningful improvement in 6-minute walk distance from baseline at 24 weeks. Eight of nine secondary efficacy outcome measures achieved statistical significance, including the outcome measure of proportion of participants achieving multicomponent improvement level, and either improvement in 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.

The Cognitive/Emotional Impacts domain score of PAH-SYMPACT, which was assessed as the ninth and final secondary outcome measure, did not achieve statistical significance. The overall safety profile of sotatercept in STELLAR was in general consistent with what has been observed in phase 2. Results from the study will be presented at an upcoming scientific congress.

“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. The results from the secondary efficacy outcomes, including a favorable benefit seen in patients’ time to a clinical-worsening event, are especially noteworthy,” said Dean Li, president, Merck Research Laboratories. “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.”

STELLAR is a pivotal phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study designed to evaluate the safety and efficacy of sotatercept compared to placebo, as an add-on to background therapy for the treatment of adults with pulmonary arterial hypertension. The primary endpoint is exercise capacity, as measured by 6-minute walk distance 24 weeks following initiation of treatment. Nine secondary outcome measures were assessed.

Author: Rare Daily Staff