RESULTS from the OPEN-LABEL EXTENSION PERIOD of A PHASE 2 TRIAL EVALUATING the SAFETY and EFFICACY of POZELIMAB and CEMDISIRAN COMBINATION in PATIENTS with PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA.

Jang, J.-H.; Raymond Wong, S.M.; Pavani, R.; Aurand, L.; Nguyen, Q.P.; Perlee, L.; Souttou, A.; Kelly, R.

RESULTS from the OPEN-LABEL EXTENSION PERIOD of A PHASE 2 TRIAL EVALUATING the SAFETY and EFFICACY of POZELIMAB and CEMDISIRAN COMBINATION in PATIENTS with PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA.

All Authors

Jang, J.-H.

Raymond Wong, S.M.

Pavani, R.

Aurand, L.

Nguyen, Q.P.

Perlee, L.

Souttou, A.

Kelly, R.

LTHT Author

Kelly, Richard

LTHT Department

Oncology
Haematology

Publication Date

2024

Item Type

Conference Abstract

Subject

ADULT , AGED , RECTAL FISTULA , BLOOD TRANSFUSION , CONTROLLED CLINICAL TRIALS AS TOPIC , DOSAGE FORMS , SUBSTANCE WITHDRAWAL SYNDROME , WOMEN , FOLLOW-UP-STUDIES , INJECTIONS , INTESTINAL POLYPS , INTESTINE, LARGE , MEN , HAEMOGLOBINURIA , CLINICAL TRIALS AS TOPIC , RANDOMISED CONTROLLED TRIAL , DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS , HAEMOGLOBINS , ANTIBODIES, MONOCLONAL , MENINGOCOCCAL VACCINES , ANTIGENS

Abstract

Background: Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-rare disease characterised by chronic intravascular haemolysis due to uncontrolled complement activation. Cemdisiran and pozelimab are investigational treatments that act together to suppress terminal complement activity. Cemdisiran is an N-acetylgalactosamine-conjugated small interfering RNA that suppresses liver production of complement component C5, while pozelimab is a fully human monoclonal antibody inhibitor of C5. The combination of pozelimab and cemdisiran was evaluated in a Phase 2 study (NCT04811716) that enrolled patients with PNH who had transitioned from pozelimab monotherapy. Aim(s): To present safety and efficacy data from the completed optional open-label extension period (OLEP) of this phase 2 trial. Method(s): The study consisted of four periods: a screening period (7-8 days), an open-label treatment period (OLTP; 28 weeks), an optional OLEP (52 weeks), and a post-treatment safety follow-up period (52 weeks). Patients (n=24; all had received meningococcal vaccination) were randomised (1:1) into one of two treatment arms during the previous OLTP; 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). During the OLEP, all patients received cemdisiran 200 mg Q4W plus pozelimab 400 mg SC Q4W. Result(s): In total, 23 patients entered the optional OLEP; 22 completed the OLEP and one from arm 2 withdrew consent and discontinued treatment. During the OLEP, all patients maintained adequate control of lactate dehydrogenase (<=1.5 x upper limit of normal) at all time points through to Week 52. Most patients (78.3%, n=18) met the criteria for haemoglobin stabilisation (did not receive a blood transfusion and had no decrease in haemoglobin >=2 g/dL) through to Week 24 of the OLEP, with a similar proportion through Week 52 (69.6%, n=16). Transfusion avoidance was achieved by 20 (87.0%) patients through Week 52 of the OLEP. CH50, a measure of total complement haemolysis activity, remained fully suppressed in all patients at all post-baseline time points. During the OLEP, 17 patients (73.9%) experienced a total of 38 treatment-emergent adverse events (TEAEs); the majority of events were mild/moderate and none resulted in treatment discontinuation. The most common treatment-related TEAE during the OLEP was injection-site reaction, experienced by three (13.0%) patients. Breakthrough haemolysis (a severe TEAE) occurred in one patient. Two patients (8.7%) experienced serious TEAEs; one experienced haemolysis, and one experienced anal fistula and large intestine polyp. There were no meningococcal infections, thrombotic events or deaths during the OLEP. Summary/Conclusion: During the OLEP, the combination of pozelimab and cemdisiran was generally well tolerated in patients with PNH. All patients maintained adequate control of haemolysis for the duration of the OLEP on a Q4W dosing regimen of pozelimab and cemdisiran. Most patients (69.6%) achieved haemoglobin stabilisation for the duration of the 52-week OLEP. These findings support the ongoing development of this combination therapy in the treatment of patients with PNH. (Figure present).