Merck’s Sotatercept Trial Results for Treatment of Adults With PAH Meet Primary Endpoint

The STELLAR phase 3 trial (NCT04576988) evaluating sotatercept (Merck) as an add-on therapy to stable background therapies, met its primary efficacy outcome measure, demonstrating a clinically meaningful and statistically significant improvement in 6-minute walking distance (6MWD) from baseline at 24 weeks for the treatment of pulmonary arterial hypertension (PAH).¹

Sotatercept is an investigational activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein. In the study, 6MWD was defined as how far a patient can walk in 6 minutes.¹

“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 6-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,” Dean Li, MD, PhD, president of Merck Research Laboratories, said in a statement.

“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,” he said.¹

Additionally, 8 of the 9 secondary efficacy outcomes measured were statistically significant, including the outcome measure of proportion of individuals achieving multicomponent improvement, defined as and either improvement in WHO FC or maintenance of WHO FC II, improvement in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and improvement of 6MWD.¹

This also included the outcome measure of time to death or first occurrence of clinical worsening event (TTCW).¹

Other secondary endpoints included change from baseline in the Cardiopulmonary Symptoms domain score of PAH-SYMPACT; change from baseline in NT-proBNP levels; change from baseline in the Physical Impacts domain score of PAH; change from baseline in pulmonary vascular resistance; proportion of individuals who improved in WHO FC; and proportion of individuals who achieved or maintained a low-risk score using the simplified French Risk score calculator.¹

However, the Cognitive/Emotional Impacts domain score of PAH-SYMPACT did not achieve statistical significance.¹

The overall safety profile was generally consistent with the profile observed in phase 2.1

STELLAR was a double-blind, multicenter, parallel-group, placebo-controlled, randomized, study.¹

The study results will be presented at an upcoming scientific congress.¹

Sotatercept was designed to rebalance pro-proliferative and anti-proliferative signaling associated with the pulmonary arterial wall and the right ventricular remodeling.¹

It has been granted breakthrough designation by the FDA and priority medicine designation by the European Medicines Agency for the treatment of PAH.¹

Merck acquired the exclusive rights to the drug in the pulmonary hypertension field because of the acquisition of Acceleron Pharma Inc. It is also part of a licensing agreement with Bristol Myers Squibb.¹

PAH occurs when the pressure in the blood vessels leading to the heart and the lungs is too high, according to the CDC.

It is most common among individuals aged 75 or older, non-Hispanic Black individuals, and women.²

Reference

1. Merck announces positive top-line results from pivotal phase 3 STELLAR trial evaluating sotatercept for the treatment of adults with pulmonary arterial hypertension (PAH). News release. Merck. October 10, 2022. Accessed October 11, 2022. https://www.merck.com/news/merck-announces-positive-top-line-results-from-pivotal-phase-3-stellar-trial-evaluating-sotatercept-for-the-treatment-of-adults-with-pulmonary-arterial-hypertension-pah/

2. Pulmonary hypertension. CDC. Updated December 3, 2019. Accessed October 11, 2022. https://www.cdc.gov/heartdisease/pulmonary_hypertension.htm