PATIENT-REPORTED OUTCOMES from A PHASE 3, RANDOMIZED TRIAL EVALUATING the COMBINATION of POZELIMAB and CEMDISIRAN in PATIENTS with PAROXYSMAL NOCTURNAL HEMOGLOBINURIA.

Hartford, C.; Griffin, M.; Jang, J.; Dain, B.; Magyar, A.; Delevry, D.; Taneja, D.; Aurand, L.; Perlee, L.; Patriquin, C.

PATIENT-REPORTED OUTCOMES from A PHASE 3, RANDOMIZED TRIAL EVALUATING the COMBINATION of POZELIMAB and CEMDISIRAN in PATIENTS with PAROXYSMAL NOCTURNAL HEMOGLOBINURIA.

All Authors

Hartford, C.

Griffin, M.

Jang, J.

Dain, B.

Magyar, A.

Delevry, D.

Taneja, D.

Aurand, L.

Perlee, L.

Patriquin, C.

LTHT Author

Griffin, Morag

LTHT Department

Oncology
Haematology

Publication Date

2025

Item Type

Conference Abstract

Abstract

Background Paroxysmal nocturnal hemoglobinuria (PNH), an ultra-rare, acquired, life-threatening disease, is characterized by uncontrolled complement activation. The combination of pozelimab + cemdisiran is being investigated for its ability to achieve complete, durable suppression of complement component C5. Here, we present patient-reported outcomes from a completed exploratory cohort (Cohort A) of an ongoing, open label Phase 3 study evaluating the effect of pozelimab + cemdisiran versus ravulizumab in patients with active PNH who are complement inhibitor treatment-naive or have not recently received complement inhibitor therapy (NCT05133531). Methods Patients were randomized 1:1 to pozelimab + cemdisiran or ravulizumab. Patients in the pozelimab + cemdisiran arm received a 30 mg/kg intravenous (IV) loading dose of pozelimab on Day 1, followed by pozelimab 400 mg + cemdisiran 200 mg subcutaneously once every 4 weeks. Those assigned to ravulizumab received IV treatment every 8 weeks after an initial loading regimen, as per the prescribing information. Secondary endpoints included change from baseline to Week 26 on 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/quality of life (GHS/QoL) and physical function scales (score range 0-100). Higher scores indicate less fatigue, improved GHS/QoL, or greater physical function. Results Overall, 48 patients were randomized, 25 to the pozelimab + cemdisiran arm and 23 to the ravulizumab arm. For FACITFatigue, mean (standard deviation [SD]) baseline scores were 36.0 (10.8) for the pozelimab + cemdisiran arm and 38.7 (11.2) for the ravulizumab arm; at Week 26, mean change from baseline was 4.9 (10.1) and 3.5 (9.2), respectively. For GHS/QoL, mean (SD) baseline scores were 55.6 (23.2) for the pozelimab + cemdisiran arm and 62.1 (18.0) for the ravulizumab arm; at Week 26, mean change from baseline was 17.6 (25.3) and 12.1 (16.4), respectively. For physical function, mean (SD) baseline scores were 72.1 (20.0) for the pozelimab + cemdisiran arm and 82.1 (16.4) for the ravulizumab arm; at Week 26, mean change from baseline was 9.0 (15.3) and 4.5 (14.8), respectively. Summary/Conclusion Improvements were observed for FACIT-fatigue, GHS/QoL, and physical function scores for both pozelimab + cemdisiran and ravulizumab arms. Though Cohort A was not sized to achieve statistical significance for these endpoints, numericallygreater improvements were observed with pozelimab + cemdisiran therapy compared with ravulizumab.