Merck Reports Positive Results for Experimental PAH Therapy

Rare Daily Staff

Merck reported full results from the phase 3 STELLAR trial of its experimental therapy sotatercept in combination with stable background therapy for the treatment of adult patients with pulmonary arterial hypertension, which showed it significantly improved exercise capacity.

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. Approximately 40,000 people in the U.S. 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.

Sotatercept is an experimental, potential first-in-class activin signaling inhibitor biologic being studied for the treatment of PAH. PAH is, in part, caused by hyperproliferation of cells in the arterial walls in the lung, leading to narrowing and abnormal constriction. In pre-clinical models, sotatercept has been shown to modulate vascular cell proliferation, reversing vascular and right ventricle remodeling.

Sotatercept has been granted Breakthrough Therapy Designation and Orphan Drug designation by the U.S. Food and Drug Administration, 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.

STELLAR was a pivotal Phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the safety and efficacy of sotatercept. The study enrolled a total of 323 participants who were randomized to receive either sotatercept once every three weeks at a dose of 0.3 mg/kg at visit 1 and a dose of 0.7 mg/kg thereafter or placebo added to stable background PAH therapy.

Patients treated with sotatercept increased 6-minute walk distance (6MWD) by 40.8 meters from baseline at week 24, the study’s primary endpoint. In addition, sotatercept demonstrated statistically significant and clinically meaningful improvements in eight of nine secondary outcome measures, including improvements in WHO functional class (WHO FC) and pulmonary vascular resistance (PVR).

Sotatercept reduced the risk of clinical worsening or death by 84 percent compared to placebo with a median follow-up of 32.7 weeks. The safety profile of sotatercept was generally consistent with that observed in previous studies with sotatercept. These data were presented at the American College of Cardiology’s 72^nd Annual Scientific Session together with World Heart Federation’s World Congress of Cardiology and simultaneously published in The New England Journal of Medicine.

Treatment-emergent adverse events (TEAEs) occurred in 90.8 percent of patients who received sotatercept versus 91.9 percent of patients who received placebo, while severe TEAEs were observed in 12.9 percent versus 18.1 percent of patients, respectively. Adverse events that occurred more frequently with sotatercept versus placebo were bleeding events, telangiectasia, increased hemoglobin levels, thrombocytopenia, increased blood pressure, and dizziness.

“The results from the phase 3 STELLAR trial are immensely important to physicians and patients and highlight the critical role sotatercept may play in improving exercise capacity and other meaningful clinical outcome measures for patients with PAH,” said Dean Li, president, Merck Research Laboratories. “These findings are compelling given the profound reduction in the risk of clinical worsening or death in patients treated with sotatercept on top of background therapy.”