Rӧth, Alexander, Barcellini, Wilma, Ademokun, Christine, Jang, Junho, Lozano, Maria Luisa, Ferreiras, David Valcarcel, Izquierdo, Cristina Pascual, Chitnis, Shripad, Matviykiv, Sofiya, Vitaliti Garami, Alessandra, Chen, Chi-2, Katsanou, Vasiliki, Chawla, Raghav and Al-Samkari, Hanny Al-Samkari (2025) Iptacopan for Immune Thrombocytopenia and Cold Agglutinin Disease: A Global Phase II Basket Clinical Trial. American journal of hematology. pp. 1-13. ISSN 1096-8652; 0361-8609

Abstract

Iptacopan is a first-in-class, oral, selective inhibitor of complement factor B that has demonstrated positive efficacy across several complement-driven diseases. Here we evaluate the efficacy and safety of iptacopan monotherapy in adult patients with primary immune thrombocytopenia (ITP) and primary cold agglutinin disease (CAD). We performed a global, multicenter, phase II basket study (NCT05086744) enrolling patients with primary ITP or CAD after failure of ≥1 unique prior therapies. Primary endpoints were platelet response (≥50×109/L) for ITP and hemoglobin response (≥1.5 g/dL increase) for CAD sustained for ≥2 consecutive weeks during the first 12 weeks of iptacopan treatment, without the use of rescue therapy. Other endpoints included time to first response, duration of response, pharmacokinetics, safety/tolerability, and FACIT-Fatigue. Nineteen patients were treated with iptacopan (9 ITP, 10 CAD). Five (50%) patients with CAD met the primary endpoint, with a mean increase in hemoglobin from baseline to week 12 of 2.2 g/dL. Improvements were also observed for other outcomes in CAD, including lactate dehydrogenase, bilirubin, reticulocytes, and FACIT-Fatigue. Conversely, no patients with ITP met the primary endpoint. Most treatment-emergent adverse events (TEAEs) were mild, the most common being headache (21%), asthenia (16%), fatigue (16%), and petechiae (16%). In conclusion, iptacopan monotherapy demonstrated encouraging preliminary efficacy in primary CAD, while no protocol-defined responses were observed in primary ITP. Iptacopan may represent a promising oral option for CAD and was well tolerated in both ITP and CAD with no unexpected safety signals.

Item Type:	Article
Date Deposited:	24 Dec 2025 00:45
Last Modified:	24 Dec 2025 00:45
URI:	https://oak.novartis.com/id/eprint/57973