Merck announced that the Phase III STELLAR clinical study of sotatercept in pulmonary arterial hypertension (PAH) achieved positive top-line results, meeting the primary endpoint and multiple secondary endpoints.
Sotatercept is an ACVR2A-Fc fusion protein composed of the extracellular domain of human Activin receptor IIA fused to the Fc domain of IgG1, which can bind and capture TGF-β family ligands (TGF-β ligand traps), This in turn restores the balance of the BMPR-2 signaling pathway. Since the imbalance of BMPR-II signaling is the driving factor of PAH, sotatercept achieves the therapeutic purpose of alleviating inflammation in patients with pulmonary arterial hypertension by this mechanism.
STELLAR is a randomized, double-blind, placebo-controlled, multicenter, parallel-group pivotal Phase III study to evaluate the safety and efficacy of sotatercept as an add-on treatment to background therapy in adults with PAH.
The results showed that after 24 weeks of treatment, patients achieved a statistically significant and clinically significant improvement in 6-minute walk distance (6MWD), meeting the primary endpoint. In addition, 8 of the 9 secondary endpoints were statistically significant, including improvement in patients achieving multiple outcomes such as improvement in 6MWD, improvement in levels of NT-proBNP (commonly used to diagnose heart failure), WHO FC (functional classification of pulmonary hypertension) ) improvement or WHO FC maintained grade II level, time to death or first clinical worsening event (TTCW) improvement. The last secondary endpoint, the PAH-SYMPACT cognitive/mood impact score, did not reach statistical significance.
The safety profile of this trial was consistent with previous phase II studies.
PAH is a rare progressive and life-threatening vascular disease characterized by constriction of the small pulmonary arteries and elevated blood pressure in the pulmonary circulation that not only severely stress the heart, but also lead to limited physical activity, heart failure, and reduced life expectancy. Despite standard treatments, the disease progresses rapidly in many patients, with a 5-year mortality rate of approximately 43%.
In September 2021, Merck and Acceleron reached a $11.5 billion merger and acquisition agreement, obtaining the newly approved anemia drug Reblozyl (luspatercept) and the investigational pulmonary hypertension drug sotatercept.