Real-world clinical characteristics and treatment outcomes in PNH patients prescribed pegcetacoplan across europe, the United States and Canada Free

Background Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare blood disease characterized by uncontrolled complement activation with potentially life-threatening complications. Therapeutic options comprise both terminal complement inhibition, targeting C5 to prevent intravascular hemolysis (IVH), and proximal complement inhibition, intervening upstream within the complement cascade to address IVH and extravascular hemolysis (EVH). Pegcetacoplan, the first C3 and C3b inhibitor, demonstrated efficacy and safety in complement inhibitor (CI)–experienced (CI_exp) and –naïve (CI_naive) patients in two phase 3 studies with a three year follow up (PEGASUS [NCT03500549] and PRINCE [NCT04085601]).

The aim of this study was to describe real world clinical and treatment outcomes in CI_exp and CI_naive PNH patients prescribed 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 November 2023–January 2025 in Canada, France, Germany, Italy, Spain, the UK, and the US. Patients prescribed pegcetacoplan for ≥3 months were included and described as CI_exp if they had previously been treated with CI, or CI_naive if patients had never been prescribed CI therapy. Physicians reported patient demographics, clinical characteristics, and treatment outcomes. Patients provided data on patient-reported outcomes, including the EQ-5D-5L and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue. Response to pegcetacoplan was categorized as no, minor, partial, good, major or complete response per SAAWP-response criteria (Risitano et al, 2019). Analyses were descriptive.

Results Overall, 54 physicians provided data for 77 patients prescribed pegcetacoplan (54 CI_exp patients and 23 CI_naive patients). Median (interquartile range [IQR]) age was 45.0 (33.5–55.0) years (CI_exp, 47.0 [37.0–60.8]; CI_naive, 39.0 [30.0–45.0]), 63.6% (C_exp, 64.8%; C_naive, 60.9%) were male, 57.9% (CI_exp, 50.9%; CI_naive, 73.9%) were in employment. Median (IQR) time since diagnosis was 2.4 (1.3–4.9) years (C_exp, 3.1 [2.0–5.5]; C_naive, 1.3 [0.8–2.3]) with median (IQR) time since start of pegcetacoplan initiation being 0.6 (0.4–1.0) year (CI_exp, 0.6 [0.4–0.9]; CI_naive, 0.6 [0.5–1.2]).

Clinical outcomes were measured at treatment initiation and the time of survey, and reported as median (IQR). Hemoglobin levels increased from 9.0 (8.0–9.2) to 11.0 (10.3–12.1) g/dL, and 9.0 (7.0–10.5) to 11.5 (10.6–12.0) g/dL, for C_exp (n=52) and C_naive (n=21), respectively. Lactate dehydrogenase levels decreased from 490 (295–594) to 260 (189–377) U/L for C_exp (n=53), and 275 (214–775) to 220 (187–278) U/L for C_naive (n=18). Absolute reticulocyte counts decreased from 200 (135–275) to 113 (105–217) x10⁹/L for C_exp (n=19) and 160 (113–250) to 110 (100–134) x10⁹/L for CI_naive (n=7).

Positive movement by at least one response category since pegcetacoplan initiation were observed in 85.2% CI_exp (n=27) and 61.5% CI_naive (n=13); with patients classified as having a ‘good’, ‘major’ or ‘complete’ response increasing from 3.7% to 74.1% for CI_exp and 23.1% to 69.2% for CI_naive.

Perceived severity of PNH improved after pegcetacoplan initiation, with ‘mild’ severity increasing from 13.0% to 68.5% and 34.8% to 87.0%; patients experiencing no fatigue increased from 5.6% to 57.4% and 8.7% to 65.2%, for CI_exp and CI_naive, respectively.

For both CI_exp and CI_naive, complete treatment adherence was reported for 87.0% of patients. Since pegcetacoplan initiation, proportion of ‘well’ or ‘very well’ controlled PNH patients increased from 14.8% to 96.3% for CI_exp and 52.2% to 100.0% for CI_naive.

Overall, 25 patients self-reported data (n=14 CI_exp; n=11 CI_naive). Patients reported a mean (Standard Deviation [SD]): EQ-5D VAS score of 66.8 (16.0) and 76.7 (18.7); EQ-5D utility score of 0.86 (0.16) and 0.91 (0.13); FACIT-Fatigue 41.1 (9.5; n=13)and 37.1 (12.2; n=11) for CI_exp and CI_naive, respectively.

Conclusion Improvements in clinical values, perceived PNH severity, control of PNH, and both physician and patient-reported fatigue were observed in CI_exp and CI_naive patients. These data suggest that pegcetacoplan has positive outcomes regardless of prior CI exposure. These findings indicate that the efficacy of pegcetacoplan in a real-world clinical practice is consistent with results from clinical trials and other real-world evidence for both CI_exp and CI_naive patients.