Current Real-World Treatment Landscape for Patients with Paroxysmal Nocturnal Hemoglobinuria in the United States

Introduction: Treatment options have historically been limited for patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare, life-threatening hematological disorder. However, since the first complement-inhibitor (CI) approval in 2007, therapeutic complement inhibition has revolutionized the treatment of PNH. In December 2023, iptacopan was approved as the first orally administered monotherapy for patients with PNH in the United States (US). Since then, two more CIs have been approved (danicopan and crovalimab). With an increasing number of CIs available for PNH, timely real-world evidence is needed to inform treatment decision-making. The objective of this study was to describe the current real-world treatment landscape among patients with PNH in the US.

Methods: This retrospective, observational cohort study used both US closed (insurance provider records) and open claims data (health system and pharmacy records) from Komodo's Healthcare Map™. The study included adults (age ≥18 years) with ≥2 distinct claims with a PNH diagnosis between January 1, 2018 and June 14, 2024. Patients were classified into two mutually exclusive cohorts based on their CI therapy use in the identification period (June 14, 2023 to June 14, 2024): CI-treated (those with ≥2 consecutive paid claims for CI therapy) and CI-untreated (those with ≥1 paid claim associated with a PNH diagnosis and ≤1 paid claim for CI therapy). CI therapies included eculizumab, ravulizumab, pegcetacoplan, iptacopan, danicopan, and crovalimab. The index date was defined as the start date of the most recent CI therapy received for the CI-treated cohort and the date of the earliest claim with a PNH diagnosis within the identification period for the CI-untreated cohort. All patients were required to have continuous enrollment for ≥90 days prior to the index date. It should be noted that this study will be updated with additional patients and clinical outcomes, including laboratory data, which will be available at the time of presentation.

Results: A total of 1,090 patients met the study inclusion criteria, of whom 369 (34%) were CI-treated (median age 49 years [interquartile range (IQR) 35-64 years], 58% female, 36% White, 10% Black, 8% Asian, and 55% covered by commercial insurance) and 721 (66%) were CI-untreated (median age 52 years [IQR 34-67 years], 56% female, 44% White, 10% Black, 7% Asian, and 48% covered by commercial insurance). The distribution of claims for the most recent CI therapy were as follows: pegcetacoplan (41.7%), ravulizumab (34.7%), iptacopan (13.8%), eculizumab (9.5%), danicopan (0.3%), and crovalimab (0%). Of the three most recently approved CI therapies, iptacopan had the highest number of patients with claims (n=51) and real-world data available; one patient had claims for danicopan and none for crovalimab. Among the 51 patients with iptacopan claims, the median age was 53 years (IQR 35-66 years); 65% were female, 41% were White, 6% were Black, 18% Asian, and 63% were covered by commercial insurance. At the start of iptacopan therapy, patients who had a claim for prior CI therapy were most commonly patients switching from pegcetacoplan and ravulizumab. The remaining patients did not have any claim for CI therapy in the 6 months prior to the index date.

Conclusions: This study provides early insights into the current real-world treatment landscape for patients with PNH. Following its approval, uptake of iptacopan among patients with PNH has been rapid in US real-world clinical practice, with 14% of CI-treated patients currently receiving iptacopan as their most recent therapy. Nonetheless, the majority of included patients with PNH did not have a claim for a CI therapy during the study period, despite the availability of six approved CI therapies.

Tomassetti:Genentech: Research Funding; Sanofi: Research Funding; Merck: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; Kartos: Research Funding; Seagene: Research Funding; Pfizer: Research Funding; Principia: Research Funding; Beigene: Research Funding; Proctor and Gamble: Current holder of stock options in a privately-held company; Eli Lili: 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. Buchan:Novartis Pharmaceuticals Corporation: Consultancy. Buchan:2Novartis Pharmaceuticals Corporation: Consultancy. Tang:2Novartis Pharmaceuticals Corporation: Consultancy. Kim:2Novartis Pharmaceuticals Corporation: Consultancy. Yen:Novartis Pharmaceuticals Corporation: Current Employment, Current holder of stock options in a privately-held company.