Real-World Characteristics and Treatment History of Patients with Paroxysmal Nocturnal Hemoglobinuria Initiating Iptacopan in US Administrative Claims Data
Authors: Shammo Jamile , Bilano Ver , Noshad Sina , Geevarghese Lincy , Yen Glorian , Paulose Jincy , Sorg Rachael , Boyd Marley , Keshishian Allison , Kim Sonia , Tomicki Samantha , Lee Soyon 
Published: December 2024

Introduction
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening, clonal hematopoietic stem cell disorder and if left untreated, can lead to serious morbidity. The introduction of complement inhibitors (Ci) since 2007 has significantly improved patient outcomes. Iptacopan, a first-in-class factor B inhibitor, received approval from the U.S. Food and Drug Administration on December 5, 2023. Given its recent approval, there is currently a lack of real-world evidence characterizing treatment history of patients with PNH initiating iptacopan. This study describes characteristics and treatment journeys landscape among patients with PNH prior to initiating iptacopan in the US.
Methods
This was an initial exploratory analysis with data derived from a retrospective observational cohort study that analyzed closed claims and linked labs of patients with PNH, aggregated by HealthVerity between October 1st, 2015, and May 30th, 2024. The curated data types included medical claims, pharmacy claims, laboratory data, and hospital chargemaster. For this analysis, we included patients aged ≥18 years with a PNH clinical diagnosis who received at least one prescription fill for iptacopan. The earliest prescription fill for iptacopan was defined as the index date. The baseline period was defined as 12 months of continuous enrollment in medical benefits prior to the iptacopan initiation index. For treatment history, the lookback period for Ci treatments included the entire enrollment period prior to the index date, while the lookback period for PNH-related concomitant non-Ci treatments (e.g. antibiotics, corticosteroids) was limited to 12 months prior to the index date. Patients were considered treatment switchers if they began iptacopan within specific treatment gaps: a 42-day gap after the end of the supply/duration of benefit for eculizumab, a 112-day gap for ravulizumab, and a 7-day gap for pegcetacoplan.
Results
Based on the interim data (May 2024), a total of 14 patients initiating iptacopan were included in the present analysis. The median (IQR) age was 47 (31, 59) years. Of these 14 patients, 71% were female, and 29% were male. Among patients with available hemoglobin measurements during the baseline period (43%), the mean (SD) hemoglobin level was 9.7 (2.9) g/dL. For PNH-related concomitant non-Ci treatments, the majority (79%) received antibiotics prior to iptacopan initiation. Other therapies included corticosteroids (43%), anti-thrombotics (7%), immunosuppressants (7%), and iron replacement/chelation therapies (7%).
A total of 11 patients (79%) had prior exposure to another Ci treatment, while 21% did not have any prior Ci treatment before iptacopan initiation and can be considered treatment-naïve. Among patients with prior Ci exposure, 91% switched to iptacopan within the treatment gap, while 9% discontinued the prior Ci treatment and initiated iptacopan later, outside of the defined grace period. 64% had a prior history of ravulizumab treatment, while 36% switched from pegcetacoplan to iptacopan. None of the patients switched directly from eculizumab to iptacopan. However, 73% had prior exposure to eculizumab sometime during the lookback period. The median time from the most recent Ci treatment discontinuation (either ravulizumab or pegcetacoplan) to iptacopan initiation was 0.9 months (IQR: 0.3, 1.3).
Conclusion
This is among the first real-world studies describing characteristics and treatment history of US patients with PNH receiving iptacopan in clinical practice. The findings show that early iptacopan users are a mix of Ci-naïve and previously-Ci-treated patients. Most patients who initiated iptacopan had been previously treated with other Cis, primarily ravulizumab. Given the small number of patients with available information, findings need to be interpreted with caution as data become available. Updated analyses with more comprehensive data are anticipated in September. Future studies are needed to explore the reasons for switching, including the potential for inadequate hematologic response to prior Ci treatments.