FDA Grants Priority Review for Merck’s Sotatercept to Treat Adults with Pulmonary Arterial Hypertension

Rare Daily Staff

The U.S. Food and Drug Administration (accepted for priority review a new Biologics License Application for sotatercept, Merck’s novel investigational activin signaling inhibitor, for the treatment of adult patients with pulmonary arterial hypertension.

The FDA has set a target action date of March 26, 2024.

Pulmonary arterial hypertension (PAH) is a rare, progressive, and ultimately life-threatening disease characterized by the narrowing of blood vessels in the lungs, causing significant strain on the heart. PAH is caused by hyperproliferation of cells in the arterial walls in the lung, leading to narrowing and abnormal constriction. Approximately 40,000 people in the United States are living with PAH. The disease progresses rapidly for many patients. PAH results in significant strain on the heart, leading to limited physical activity, heart failure, and reduced life expectancy. The five-year mortality rate for patients with PAH is approximately 43 percent.

In pre-clinical models, sotatercept has been shown to modulate vascular cell proliferation, reversing vascular and right ventricle remodeling.

The application for sotatercept is based on data from the phase 3 STELLAR trial, in which sotatercept on top of background therapy demonstrated a statistically significant and clinically meaningful improvement in 6-minute walk distance (6MWD) and eight of nine secondary outcome measures. These results were presented at ACC.23/WCC and published in The New England Journal of Medicine.

“Despite advances in the treatment of PAH over the last two decades, there is still a significant need to improve outcomes for patients,” said Joerg Koglin, senior vice president, global clinical development, Merck Research Laboratories. “Based on the profound improvements across primary and secondary outcome measures in the phase 3 STELLAR trial, we believe sotatercept has the potential to transform the treatment of patients with PAH.”

STELLAR was a pivotal phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the safety and efficacy of sotatercept in adult patients with PAH being treated with background therapy. The primary endpoint of the study was exercise capacity, as measured by change from baseline in week 24 6MWD. Nine secondary endpoints, tested hierarchically in the following order, were multicomponent improvement, change in pulmonary vascular resistance (PVR), N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, improvement in WHO FC, time to clinical worsening or death, French risk score, and the PAH-SYMPACT Physical Impacts, Cardiopulmonary Symptoms and Cognitive/Emotional Impacts domain scores; all assessed at week 24 except clinical worsening, which was assessed when the last patient completed the week 24 visit.

In addition to STELLAR, the sotatercept clinical development program includes multiple phase 2 and 3 trials across a broad range of patients. Studies are underway in adult patients with PAH at intermediate or high risk of disease progression or mortality, as well as with pulmonary hypertension due to left heart disease.

Sotatercept has been granted Breakthrough Therapy and Orphan Drug designations by the FDA, as well as Priority Medicines designation and Orphan Drug designation by the European Medicines Agency 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.

Photo: Joerg Koglin, senior vice president, global clinical development, Merck Research Laboratories