Clinical Experience of Iptacopan in Paroxysmal Nocturnal Hemoglobinuria.

Abstract

Iptacopan, an oral Factor B inhibitor, is approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). In clinical trials it was safe and effective but real-world data, particularly in patients with associated bone marrow failure, remain limited. A retrospective, multicenter study was conducted in patients with PNH who received iptacopan monotherapy in the UK and France between July 2021 and July 2025. Patient demographics, prior treatment and indication for switch were collected, as were hematological parameters at baseline, 3, 12 and 24 months. Outcomes included breakthrough hemolysis, infections, thrombotic events, treatment discontinuation and death. A total of 151 patients were included with a median treatment duration of 238 days. Iptacopan produced significant increases in mean hemoglobin, from 104 g/L at baseline to 127 g/L at 3 months, with improvements sustained to 24 months. A total of 76% achieved a hemoglobin ≥ 120 g/L by 12 months, compared with 21.9% at baseline, with transfusion independency in 88%. There was no statistical difference in responses between patients with and without history of bone marrow failure. Breakthrough hemolysis occurred in 6.6% of patients, with a mean hemoglobin fall of 24 g/L. Suspected bacterial infections occurred at a rate of 0.18 per patient-year, but there were no meningococcal or pneumococcal infections. There were no thromboses, and no deaths related to iptacopan. This cohort demonstrates that iptacopan produces sustained improvements in patients with PNH, irrespective of prior complement inhibition or history of bone marrow failure. Longer follow-up is needed to characterize long-term efficacy and infection risk.