Postmarketing analysis of sotatercept: identifying serious unlabelled events

Purpose Sotatercept, an activin signalling inhibitor approved in March 2024 for pulmonary arterial hypertension (PAH), demonstrated efficacy in clinical trials. This pharmacovigilance study evaluated its real-world safety profile using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to identify postmarketing risks. Methods FAERS reports from 2024 were analysed, focusing on cases where sotatercept was designated as the primary suspect. Duplicate entries were removed using standardised FDA protocols. Adverse events (AEs) were categorised using the Medical Dictionary for Regulatory Activities (MedDRA V.28.0). Disproportionality signals were assessed via reporting ORs (RORs; 95% CI lower limit >1 with ≥3 cases). Severity was classified using the EudraVigilance Important Medical Events (IMEs) list. Results Among 1 484 350 deduplicated reports, 613 sotatercept-associated AEs (1717 occurrences, 395 MedDRA terms) were identified. Disproportionality analysis revealed 48 safety signals: 30 aligned with labelled risks (eg, haemoglobin elevation (ROR=272.2), telangiectasia (ROR=334.1)) and 18 novel signals. The most frequent AEs included headache (n=78), epistaxis (n=57) and diarrhoea (n=53). Two unlabelled events—cerebral haemorrhage and ascites—met criteria for critical IMEs. Most reports originated from the USA (98.5%) and involved females (73.6%). Conclusion This study confirms sotatercept’s labelled risks (haematological and vascular effects) and identifies novel safety concerns, including cerebral haemorrhage and ascites, highlighting the need for vigilant monitoring in PAH management. Real-world data underscore the value of postmarketing surveillance for detecting rare or unanticipated AEs. Clinicians should prioritise monitoring for haematological abnormalities and bleeding risks. Longitudinal studies are warranted to clarify long-term safety outcomes.