EVALUATING the SAFETY and EFFICACY of POZELIMAB and CEMDISIRAN in PATIENTS with PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA: PATIENT-REPORTED OUTCOMES from the PHASE 2 OPEN-LABEL EXTENSION STUDY.

Hartford, C.; Nguyen, Q.P.; Delevry, D.; Lum, C.; Pavani, R.; Aurand, L.; Rofail, D.; Kelly, R.

EVALUATING the SAFETY and EFFICACY of POZELIMAB and CEMDISIRAN in PATIENTS with PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA: PATIENT-REPORTED OUTCOMES from the PHASE 2 OPEN-LABEL EXTENSION STUDY.

All Authors

Hartford, C.

Nguyen, Q.P.

Delevry, D.

Lum, C.

Pavani, R.

Aurand, L.

Rofail, D.

Kelly, R.

LTHT Author

Kelly, Richard

LTHT Department

Oncology
Haematology

Publication Date

2024

Item Type

Conference Abstract

Subject

ABDOMINAL PAIN , ADULT , CONTROLLED CLINICAL TRIALS AS TOPIC , DRUG THERAPY , SURVEYS AND QUESTIONNAIRES , FATIGUE , WOMEN , OUTCOME ASSESSMENT , HEALTH STATUS , MEN , HAEMOGLOBINURIA , CLINICAL TRIALS AS TOPIC , QUALITY OF LIFE , DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS , ANTIBODIES, MONOCLONAL , ANTIGENS

Abstract

Background: Paroxysmal nocturnal haemoglobinuria (PNH), an ultra-rare, chronic, progressive, acquired genetic disease, causes intravascular haemolysis and an increased tendency to develop thrombosis through uncontrolled complement activation of red blood cells, white blood cells and platelets. Symptoms of PNH which can have a negative impact on a patient's physical functioning and health-related quality of life (QoL) include severe fatigue, dyspnoea and abdominal pain. A combination therapy of pozelimab (an investigational fully human monoclonal antibody inhibitor of complement component C5) and cemdisiran (an investigational N-acetylgalactosamine-conjugated small interfering RNA that suppresses liver production of C5) is in development for patients with PNH. The 52-week safety and efficacy of the combination of pozelimab and cemdisiran following the phase 2, randomised, open-label, two-arm study were assessed (NCT04811716); patient-reported outcomes were also assessed. Aim(s): To present patient-reported outcomes data from the optional open-label extension period (OLEP) of the study. Method(s): Following completion of the randomised, open-label, two-arm, 28-week treatment period, patients were offered the opportunity to continue into the optional 52-week OLEP. During the OLEP, all patients received subcutaneous (SC) cemdisiran 200 mg every 4 weeks (Q4W) plus pozelimab 400 mg SC Q4W. Patients completed the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale (range 0-52), and the European Organization for Research and Treatment of Cancer: Quality-of-Life Questionnaire to determine changes in global health status (GHS)/QoL and physical function (range 0-100). Higher scores indicate less fatigue, a better level of functioning or better GHS/QoL. Result(s): Amongst the 24 patients who previously completed the OLTP, 23 entered the OLEP; one discontinued, and 22 completed the OLEP. At OLEP baseline, mean (standard deviation [SD]) values were 42.9 (8.61) for FACIT-Fatigue scores, 74.6 (20.33) for GHS/QoL scores, and 92.7 (12.33) for physical functioning scores. At the end of the OLEP, mean (SD) values were 42.0 (8.59) for FACIT-Fatigue scores, 81.0 (17.11) for GHS/QoL scores, and 92.4 (14.65) for physical functioning scores. A sustained improvement was observed in FACIT-Fatigue and GHS/QoL scores throughout the OLTP and OLEP. The overall mean (SD) change from OLEP baseline to Week 52 values were-0.9 (5.95) for FACIT-Fatigue scores, 6.0 (13.73) for GHS/QoL scores, and-0.3 (3.93) for physical functioning scores. Summary/Conclusion: Patients with PNH who were treated with pozelimab and cemdisiran combination therapy during the OLTP and who continued on the combination therapy Q4W in the OLEP maintained improvement in fatigue, physical functioning and QoL.