Pb2044: final patient-reported outcomes from a phase 2, randomised trial evaluating the safety and efficacy of pozelimab and cemdisiran in patients with paroxysmal nocturnal haemoglobinuria

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-rare acquired genetic disease characterised by uncontrolled complement activation, which results in intravascular haemolysis and an increased tendency to develop thrombosis. PNH causes symptoms such as severe fatigue, which can negatively impact a patient’s physical functioning and health-related quality of life (QoL). Cemdisiran is an investigational N-acetylgalactosamine-conjugated small interfering RNA (siRNA) that suppresses liver production of complement component C5, while pozelimab is an investigational fully human monoclonal antibody inhibitor of C5. The combination of pozelimab and cemdisiran is being evaluated in an ongoing phase 2, randomised, open-label, two-arm study that is designed to evaluate the safety and efficacy of combination therapy in patients with PNH who transitioned from pozelimab monotherapy (NCT04811716). Aims: Here, we present patient-reported outcomes data for the open-label treatment period of the study. Methods: Twenty-four patients were randomised (1:1) to two treatment regimens; both arms received subcutaneous (SC) cemdisiran 200 mg every 4 weeks (Q4W) plus pozelimab 400 mg SC at a frequency of either Q4W (arm 1) or every 2 weeks (arm 2). Patients completed the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale (score range 0–52), and the European Organization for Research and Treatment of Cancer: Quality-of-Life Questionnaire global health status (GHS)/QoL and physical function assessments (score range 0–100). Higher scores indicate a better level of functioning, GHS/QoL, or less fatigue. Results: Prior to receiving pozelimab monotherapy, mean (standard deviation [SD]) pre-treatment values were 32.3 (15.2) for FACIT-Fatigue scores, 60.6 (22.4) for GHS/QoL scores, and 70.9 (22.5) for physical functioning scores (Table 1). For the current trial, baseline values were representative of the effect of pozelimab monotherapy that the patients were receiving prior to transitioning to the combination therapy. The mean (SD) FACIT-Fatigue score at baseline was 45.4 (5.6) for arm 1 and 45.6 (3.6) for arm 2 (Table 1). Over Weeks 2–28, the mean FACIT-Fatigue scores were 40.3–45.2 for arm 1 and 36.5–42.9 for arm 2. The mean (SD) physical functioning score at baseline was 93.3 (8.8) for arm 1 and 94.2 (9.0) for arm 2. Over Weeks 2–28, the mean physical functioning scores were 90.0–95.0 for arm 1 and 82.0–90.9 for arm 2 (Table 1). The mean (SD) GHS/QoL scores were well controlled and similar for both treatment arms at baseline (77.8 [14.4] for arm 1 and 80.2 [20.9] for arm 2). Over Weeks 2–28, the mean GHS/QoL scores were 69.2–77.3 for arm 1 and 66.7–75.8 for arm 2. Summary/Conclusion: Patients with PNH who transitioned from pozelimab monotherapy had improved baseline scores compared with pre-treatment for their GHS/QoL, physical functioning, and fatigue scores. Improvements in these scores were maintained by the combination treatment through to Week 28, particularly with the pozelimab Q4W and cemdisiran dose regimen. Although further validation of these finding in a larger data set would be needed, this evidence suggests that pozelimab and cemdisiran combination therapy, particularly the Q4W regimen, improves and maintains improvements in patient fatigue, physical functioning, and QoL.Keywords: PNH, Quality of life, PRO, Clinical trial