Sotatercept, a soluble fusion protein comprising the extracellular domain of activin receptor type IIA linked to the Fc portion of human IgG1, is a first-in-class activin signaling inhibitor under development for the treatment of pulmonary arterial hypertension (PAH). We evaluated antidrug antibody (ADA) development and determined the effects of immunogenicity on the pharmacokinetics (PKs), efficacy, and safety of sotatercept in STELLAR, a multicenter, double-blind phase III trial (NCT04576988) wherein participants with PAH were randomized 1:1 to receive sotatercept (starting dose 0.3; target dose 0.7 mg/kg) or placebo subcutaneously every 3 weeks in combination with background therapies for
Liao K, Mackenzie H, Ait-Oudhia S, Manimaran S, Zeng Y, Akers T, Yun T, and de Oliveira Pena J. (2024) The Impact of Immunogenicity on the Pharmacokinetics, Efficacy, and Safety of Sotatercept in a Phase III Study of Pulmonary Arterial Hypertension. Clin Pharmacol Ther 115():478-487 . [article]