Real-World Clinical Outcomes for Complement Inhibitor Experienced and Naïve Paroxysmal Nocturnal Hemoglobinuria Patients Prescribed Pegcetacoplan in Europe and Canada

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder, characterized by complement-mediated hemolysis, and often manifests as anemia, fatigue, dyspnea, hematuria and abdominal pain. Current treatments include inhibitors that target complement 5 (C5i), complement 3, factor B or factor D. Pegcetacoplan, an inhibitor of complement components C3 and C3b, was approved by the European Medicines Agency (EMA) in 2021. A recent expansion to the indication by the EMA has made pegcetacoplan available for the treatment of all adults with PNH who have hemolytic anemia. The aim of this study was to describe clinical outcomes for real-world complement inhibitor experienced and complement inhibitor naïve patients treated with pegcetacoplan.

Methods: Data were drawn from the Adelphi PNH II Disease Specific Programme™, a real-world cross-sectional survey of hematologists, and their consulting PNH patients. Data were collected from December 2023 – April 2024 in Canada, France, Germany, Italy, Spain, and the UK. Physicians provided data on patient demographics, laboratory values, adherence, and clinical outcomes, and patients completed the FACIT-Fatigue questionnaire. Patients prescribed pegcetacoplan for ≥3 months were included, described as complement inhibitor experienced (C_e) if they had previously been treated with C5i or complement inhibitor naïve (C_n) if they had never been treated with any complement inhibitor. Treatment adherence was defined as the patient taking medication exactly as agreed with their physician. Descriptive analyses were reported, and missing data were not imputed.

Results: 53 physicians provided data for 63 patients prescribed pegcetacoplan, including 52 C_e patients and 11 C_n patients. Mean (SD) age was 46.4 (16.1) years (C_e, 49.4 [15.8]; C_n, 32.1 [7.4]), 60.3% (C_e, 63.5%; C_n, 45.5%) were male, 48.4% (C_e, 49.0%; C_n, 45.5%) were employed (full/part time) and 44.4% (C_e, 48.1%; C_n, 27.3%) had a diagnosed concomitant condition. Median (interquartile range [IQR]) time since PNH diagnosis was 3.1 (2.0-5.5) and 1.3 (0.8-3.7) years and median (IQR) time since pegcetacoplan initiation was 0.6 (0.4-0.9) and 0.7 (0.5-1.2) years for C_e and C_n, respectively. Complete adherence to treatment was reported for 86.5% of C_e and 90.9% of C_n. From pegcetacoplan initiation to time of data collection, mean (SD) hemoglobin (Hb) level increased from 8.8 (1.1) to 11.3 (1.7) g/dL, and 7.4 (1.9) to 11.7 (1.3) g/dL, for C_e (n=50) and C_n (n=10), respectively. Mean (SD) lactate dehydrogenase (LDH) level decreased from 503.6 (268.5) to 292.5 (140.2) U/L, and 977.8 (713.4) to 358.9 (237.4) U/L, for C_e (n=51) and C_n (n=9), respectively. Mean (SD) absolute reticulocyte count changed from 92.4 (28.2) to 77.5 (28.9) x10⁹/L, and 58.8 (24.4) to 61.7 (29.4) x10⁹/L, for C_e (n=35) and C_n (n=6), respectively. Moderate/severe fatigue was reported by the physician for 76.9% of C_e patients at pegcetacoplan initiation and 21.1% at data collection, along with 72.7% of C_n patients at pegcetacoplan initiation and 9.1% at data collection. Twenty patients provided FACIT-Fatigue data (C_e, n=12; C_n, n=8) at the time of data collection. Overall, mean (SD) FACIT-Fatigue scores were 40.1 (9.3) and 34.6 (13.5) for the C_e and C_n group, respectively. Physician-reported mean (SD) annual transfusion frequencies prior to pegcetacoplan initiation were 3.4 (2.9) and 3.8 (4.2) for C_e and C_n, respectively. Of those prescribed pegcetacoplan for ≥6 months (C_e, n=29; C_n, n=8), 28% of C_e and 11% C_n required a transfusion within the 6 months prior to data collection (mean (SD) number of transfusions 0.8 (1.6) vs 0.1 (0.4), respectively). At time of survey, physicians described PNH control as “well/very well” for 96.2% of the C_e group and 100% of the C_n group, which increased from 15.4% and 9.1% at pegcetacoplan initiation, respectively.

Conclusion: Increases in mean Hb, along with decreases in LDH, and fatigue were observed in both C_e and C_n patients. These data suggest that complement inhibitor naïve patients may experience similar outcomes to those who had previously been prescribed C5i, following pegcetacoplan initiation. These findings encourage the possibility of pegcetacoplan as an efficacious therapy for both complement inhibitor experienced and naïve PNH patients in real-world practice.