Patient-Reported Improvements in Patients with PNH Treated with Iptacopan from Two Phase 3 Studies

Iptacopan, a first-in-class, oral, selective complement factor B inhibitor, demonstrated efficacy and safety as monotherapy in C5 inhibitor (C5i)-experienced (APPLY-PNH [NCT04558918]) and C5i-naive (APPOINT-PNH [NCT04820530]) patients with paroxysmal nocturnal hemoglobinuria (PNH). In APPLY-PNH and APPOINT-PNH, changes in fatigue (FACIT-Fatigue) and health-related quality of life (HRQOL; EORTC QLQ-C30) from baseline to Day 168 were evaluated. The proportion of patients achieving meaningful within-patient change (MWPC) on the FACIT-Fatigue and 4 EORTC QLQ-C30 subscales (physical functioning, role functioning, fatigue, dyspnea) was evaluated using anchor-based thresholds. Correlations between FACIT-Fatigue scores, lactate dehydrogenase (LDH), and hemoglobin (Hb) levels were also assessed. In APPLY-PNH (iptacopan, n=62; C5i, n=33), more patients in the iptacopan group reached the MWPC threshold for FACIT-Fatigue than in the C5i group (51% vs 11%). More patients achieved MWPC on domains of the EORTC QLQ-C30 in the iptacopan group (39%-49%) than the C5i group (9%-20%). In APPOINT-PNH (N=40), 56% achieved MWPC on the FACIT-Fatigue, and the proportion of patients who achieved MWPC on the EORTC QLQ-C30 ranged from 41% to 55%. In C5i-experienced patients, increased Hb levels correlated with improvement in FACIT-Fatigue scores (R=0.48, P<0.001). In C5i-naive patients treated with iptacopan, increased Hb (R=0.42, P<0.001) and decreased LDH (R=-0.53, P<0.001) correlated with improved FACIT-Fatigue scores. C5i-experienced and -naive patients receiving iptacopan exhibited meaningful improvement in fatigue, HRQOL, and disease-related symptoms, which correlated with clinical improvement in hematologic markers of disease control. These trials are registered at www.ClinicalTrials.gov as NCT04558918 (APPLY-PNH) and NCT04820530 (APPOINT-PNH).