Early Insights into Real-World Iptacopan Use Among Patients with Paroxysmal Nocturnal Hemoglobinuria in the United States: The Apprise-PNH Data Platform

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening hematological disorder affecting approximately 24 people per million in the United States (US). Iptacopan, the first orally administered monotherapy for PNH, received US Food and Drug Administration approval in December 2023. APPRISE-PNH (A Patient Platform for Real-world data on Iptacopan in the United StatEs for patients with PNH) is a data platform designed to capture comprehensive real-world information on patients with PNH treated with iptacopan in the US. This interim analysis aims to provide early insights into the characteristics and treatment patterns of patients enrolled in APPRISE-PNH to date.

Methods: APPRISE-PNH is a retrospective, longitudinal, data platform including adult patients (age ≥18 years) with PNH treated with iptacopan in the US real-world setting. Consenting patients in the US are recruited through the iptacopan distribution network. The present analysis includes data from patients enrolled between July 2 and July 26, 2024, with additional data collection expected through the remainder of 2024 and 2025. Patient characteristics and treatment patterns were evaluated descriptively. Duration of therapy was measured from the date of iptacopan initiation until the date of iptacopan discontinuation or data cut-off, whichever occurred first. Treatment adherence was measured using both the medication possession ratio (MPR), calculated as the ratio of the total days supply to days covered, and the proportion of days covered (PDC), calculated as the ratio of days with supply to days covered.

Results: As of July 26^th, 2024, nine patients with PNH have enrolled in the APPRISE-PNH data platform. The median age at the start of iptacopan therapy was 44 years (interquartile range [IQR] 40-73 years), seven (78%) patients were female, and four (44%) were covered by commercial insurance. Overall, two (22%) patients were treatment-naïve at the start of iptacopan therapy, while seven (78%) patients had received prior complement-inhibitor (CI) therapy for PNH (44% ravulizumab, 44% eculizumab, 33% pegcetacoplan). The median duration of iptacopan therapy was 2.0 months (IQR 1.5-2.9 months). All patients received iptacopan 200 mg twice daily (as per the product label) and the median number of fills was 2.0 (IQR 1.0-3.0). At the time of data cut-off, no patients had discontinued iptacopan therapy. The MPR in this group of patients was 136% (IQR 114%-150%) and PDC was 100% (IQR 100%-100%).

Conclusions: These are the first data from the APPRISE-PNH data platform and represent the first insights into real-world use of iptacopan in the US. Many patients enrolled in APPRISE-PNH had previously received CI therapy for PNH. Treatment adherence, as indicated by both the MPR and PDC, was high across iptacopan-treated patients. Enrollment into the APPRISE-PNH data platform is currently ongoing; data from additional patients, additional laboratory and clinical outcomes, and longer follow-up data are expected to be available at the time of presentation.

Dingli:K36 Therapeutics: Research Funding; Alexion: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Apellis: Consultancy, Honoraria, Research Funding; MSD: Consultancy, Honoraria; Sorrento: Consultancy, Honoraria; Genentech: Consultancy; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria. Yen:Novartis Pharmaceuticals Corporation: Current Employment, Current holder of stock options in a privately-held company. Kuypers:Novartis Pharmaceuticals Corporation: Current Employment, Current holder of stock options in a privately-held company. Paulose:Novartis Pharmaceuticals Corporation: Current Employment, Current holder of stock options in a privately-held company. Chanpura:Novartis Pharmaceuticals Corporation: Current Employment. Lee:Novartis: Current Employment, Current holder of stock options in a privately-held company. Barone:Novartis Pharmaceuticals Corporation: Consultancy. Stutts:Novartis Pharmaceuticals Corporation: Consultancy. Buchan:Novartis Pharmaceuticals Corporation: Consultancy. Buchan:2Novartis Pharmaceuticals Corporation: Consultancy. Kim:2Novartis Pharmaceuticals Corporation: Consultancy. Tang:2Novartis Pharmaceuticals Corporation: Consultancy. Waheed:Novartis Pharmaceuticals Corporation: Consultancy; Alexion: Consultancy.