Pb2043: clinical effectiveness, treatment use, satisfaction and impact on quality-of-life of pegcetacoplan treatment for patients with paroxysmal nocturnal haemoglobinuria (pnh).

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: PNH is a rare, chronic, and potentially fatal disease characterized by complement mediated premature destruction of red blood cells. Clinical manifestations include anemia, fatigue and major adverse vascular events such as thrombosis. Currently available treatments include complement protein 5 inhibitors (C5i), however some patients receiving these still remain anemic or symptomatic due to ongoing intravascular hemolysis (IVH) and emerging extravascular hemolysis (EVH). Pegcetacoplan (PEG) is the first FDA/EMA approved complement protein 3 inhibitor (C3i), for the treatment of adults with PNH demonstrating broad control of both IVH and EVH. Aims: Examine treatment use, satisfaction, clinical effectiveness, and impact on patient Quality of Life (QoL) of PEG treated patients with PNH. Methods: Data were drawn from the Adelphi PNH Disease Specific Programme™, a real-world cross-sectional survey of physicians, and their next consulting patients with PNH from January-November 2022 in the US and EU4 (France, Italy, Germany, and Spain). Patients were eligible for inclusion if prescribed PEG for ≥1 month. Physicians recorded data on patient demographics, clinical markers, treatment satisfaction, and QoL. The same patients were invited to self-report data on treatment satisfaction and QoL. Descriptive statistics are shown. Results: 14 hematologists/hematologist-oncologists provided data for 61 patients receiving PEG. Mean (SD) time since diagnosis was 3.7 (3.3) years and mean (SD) time receiving PEG was 5.9 (4.0) months. Mean (SD) patient age was 37.1 (11.3) years, 36 (59.0%) were male and 57 (93.4%) previously switched from a C5i. From PEG initiation to date of data collection, physicians reported a mean (SD) improvement in hemoglobin of 2.5 (1.9) g/dL, 2.8 (2.1) g/dL, and 3.3 (2.1) g/dL for those receiving PEG for ≥1 month (n=61), ≥3 months (n=44), and ≥6 months (n=23), respectively. Improvement in lactate dehydrogenase (LDH) was seen from PEG initiation to date of data collection (30.0% vs 57.4% reporting LDH <1.5 x ULN), and a higher proportion reported no fatigue (1.6% vs 31.1%, respectively). Physicians considered all patients to have ‘well or very well controlled’ disease and were ‘satisfied or completely satisfied’ with PEG. Physicians reported 57.4% (n=35) of patients had ‘excellent or very good’ QoL. For 91.1% (n=51/56) of patients switching from C5i to PEG, physicians reported higher satisfaction with PEG, mostly due to improved disease control (n=47/51, 92.2%). 30 patients provided self-reported data via questionnaire, of whom the mean (SD) age was 34.5 (7.3) and 15 (50.0%) were male. 96.7% (n=29) were ‘satisfied or completely satisfied’ with PEG and 92.9% (n=26) reported higher satisfaction with PEG than previous C5i, with 76.9% (n=20) attributing higher satisfaction to experiencing less fatigue. Patients reported various QoL outcomes. Mean (SD) EQ-5D Index (n=30), VAS (n=27) and FACIT-Fatigue (n=30) scores were 0.84 (0.17), 80.9 (13.3) and 37.4 (8.6), respectively. Summary/Conclusion: These findings demonstrate the real-world effectiveness of PEG through improvement in clinical markers e.g. hemoglobin, with greater improvement seen in those receiving PEG for longer. Physicians and patients reported favorable treatment satisfaction with PEG compared to previous C5i. Patients receiving PEG reported improved FACIT-Fatigue scores when compared to previously published literature for C5i, and EQ-5D-5L scores were similar to US population norms. Further research is required to explore these promising findings and support the real-world benefits of this novel treatment option for PNH Keywords: Real world data, Paroxysmal nocturnal hemoglobinuria (PNH), Complement