Real-world treatment patterns and clinical outcomes among patients with paroxysmal nocturnal hemoglobinuria treated with iptacopan in the United States

Abstract Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening hematological disorder affecting ≈24 per 1,000,000 people in the US. Iptacopan, the first orally administered monotherapy for PNH, received US Food and Drug Administration approval in December 2023. APPRISE-PNH is a data platform designed to capture comprehensive real-world information on iptacopan-treated patients with PNH. The aim of this study was to describe patient profiles and assess treatment patterns and clinical outcomes among iptacopan-treated patients (age ≥18 years) with PNH in the US real-world setting. Methods: The present interim analysis of APPRISE-PNH includes data from patients enrolled between July 2, 2024, and June 13, 2025, with additional data collection expected through 2025. Duration of therapy was measured from the date of iptacopan initiation (index) until discontinuation or data cutoff, whichever occurred first. Treatment adherence was measured using the medication possession ratio (MPR; ratio of the total days' supply to days covered) and the proportion of days covered (PDC; ratio of days with supply to days covered). Clinical outcomes were assessed during follow-up including hemoglobin (Hb; change from pre-index to highest level post index, proportion of patients with Hb increase ≥2 g/dL, and proportion of patients with Hb normalization to ≥12 g/dL), lactate dehydrogenase (LDH) (change from pre-index to lowest level post index and proportion of patients with LDH reduction <1.5× upper limit of normal [ULN]), and number of red blood cell (RBC) transfusions. Results: Among 52 patients enrolled as of June 13, 2025, the median age was 53.7 years, 38% were male, and 60% were covered by commercial insurance. Overall, 25% of patients (n=13) were complement inhibitor (CI) naive at the time of iptacopan initiation, while 75% (n=39) were treatment experienced and had received ≥1 prior CI therapy for PNH (77% ravulizumab, 46% eculizumab, 26% pegcetacoplan). All patients received iptacopan 200 mg twice daily, per the product label; the median (IQR) duration of iptacopan therapy was 9.8 (5.0-12.8) months. At the time of data cutoff, 2 patients discontinued therapy (1 due to provider decision, 1 due to death). The median (IQR) MPR and PDC were 105.2% (100.6%-110.7%) and 97.3% (92.7%-99.5%), respectively. Among the 52 patients enrolled in APPRISE-PNH, 42 patients had medical records available at the time of data cutoff. Of the 23 of 42 patients (55%) with Hb values available pre- and post index at the time of data cutoff, 4 were CI treatment naive (median [IQR] pre-index Hb, 9.9 [9.1-10.2] g/dL) and 19 were CI treatment experienced (median [IQR] pre-index Hg, 10.7 [8.9-12.2] g/dL). The median (IQR) change from pre-index to highest value post-index was similar for both groups (1.6 [0.8-2.3] g/dL and 1.6 [0.6-3.4] g/dL, respectively). However, among the CI treatment–experienced patients, those with pre-index Hb <12 g/dL (n=11) experienced a greater improvement than those with pre-index Hb ≥12 g/dL (n=8), with median (IQR) of 3.3 (2.2-4.5) g/dL vs 0.4 (0.1-1.3) g/dL, respectively. Overall, 12 of 23 patients (52%) achieved a Hb increase ≥2 g/dL, and 17 of 23 (74%) achieved Hb normalization to ≥12 g/dL. Among the 18 of 42 patients (43%) with LDH values available pre- and post index, the median (IQR) change from pre-index to lowest post-index value was −41.5 (−155.8 to 2.5) U/L. Among those with clinical data, most patients (38 of 42; 90%) did not require RBC transfusions during follow-up and 4 had evidence of an RBC transfusion over the follow-up period; 2 of 4 patients requiring transfusions had aplastic anemia and/or myelodysplastic syndrome. At the time of data cutoff, no patients with clinical data available had evidence of a major adverse vascular event (including thrombosis, transient ischemic attack, stroke, and major bleeding) over the follow-up period. Conclusions: These data represent early insights into the real-world use of iptacopan and related Hb response in US patients with PNH. Adherence to iptacopan was high, and iptacopan treatment improved Hb and LDH parameters, providing comprehensive hemolysis control. Enrollment is currently ongoing; data on additional patients with longer follow-up are forthcoming.