Patient-reported outcomes in patients with paroxysmal nocturnal hemoglobinuria treated with crovalimab and approved C5 inhibitors in the phase III COMMODORE 2 and 1 studies.

Crovalimab is a next-generation C5 inhibitor (C5i) for paroxysmal nocturnal hemoglobinuria (PNH) treatment with every-4-weeks low-volume subcutaneous maintenance dosing and the possibility for self-administration. Patient-reported outcomes (PROs) with crovalimab versus other C5is were evaluated in C5i-naive and experienced adult patients in COMMODORE 2 and 1 (NCT04434092; NCT04432584; both registered June 12, 2020), respectively. For primary analyses, patients were randomized to treatment with crovalimab or eculizumab. All patients continuing in the extension period received crovalimab. During the 24-week primary treatment period, both COMMODORE 2 arms showed rapid and sustained improvement from baseline across PROs assessing fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), other PNH symptoms (European Organisation for Research and Treatment of Cancer [EORTC] Item Library-40), and functioning and global health status/quality of life (GHS/QoL; EORTC QoL Questionnaire Core 30). In COMMODORE 1, baseline levels of PROs were maintained throughout the primary treatment period. Across studies, most patients (60–85%; including COMMODORE 1 non-randomized patients) preferred crovalimab to eculizumab or ravulizumab (Patient Preference Questionnaire), mainly driven by easier and faster administration and fewer hospital visits required. Crovalimab was rated more convenient (Treatment Satisfaction and Medication Questionnaire-9) than eculizumab across the randomized arms of both studies, with similar global satisfaction and perceived efficacy. Overall, COMMODORE 2 and 1 data on relevant aspects of health-related QoL support the treatment benefit of crovalimab from the patient perspective and show its potential as a less burdensome option than other therapies for this lifelong disease.