Safety and Efficacy of Frexalimab in Relapsing Multiple Sclerosis: 48-week Results from the Phase 2 Open-label Extension
Gavin Giovannoni1, Cristina Granziera2, Yang Mao-Draayer3, Gary Cutter4, Oleksandr Kalbus5, Ivan Staikov6, Michal Dufek7, Stephane Saubadu8, Raphael Bejuit8, Biljana Djukic8, Philippe Truffinet8, Erik Wallstroem8, Patrick Vermersch9
1Queen Mary University of London, 2Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, 3Department of Neurology, Autoimmunity Center of Excellence, University of Michigan Medical Center, 4Department of Biostatistics, University of Alabama at Birmingham (UAB) School of Public Health, 5Department of Neurology, Dnipro State Medical University, 6Clinic of Neurology and Sleep Medicine, Acibadem City Clinic University Hospital Tokuda, 71st Department of Neurology, St. Anne’s University Hospital, 8Sanofi, 9Univ. Lille, Inserm U1172 LilNCog, CHU Lille, FHU Precise
Objective:

To report safety and efficacy at Week (W) 48 in the open-label extension (OLE) of the phase 2 trial (NCT04879628) of frexalimab in participants with relapsing multiple sclerosis (RMS).

Background:

Frexalimab is a second-generation anti-CD40L monoclonal antibody that blocks the costimulatory CD40/CD40L pathway, which is important for activation and function of adaptive and innate immunity. In the 12-week double-blind period (DBP), frexalimab demonstrated safety and efficacy with the high-dose treatment showing an 89% reduction (vs placebo) in new gadolinium-enhancing (Gd+) T1-lesions. Over 24 weeks in the OLE, frexalimab was well-tolerated, and the number of lesions further decreased.

Design/Methods:

In the DBP, participants were randomized to frexalimabhigh (N=52), frexalimablow (N=51), or matching placebo arms (placebohigh, N=12; placebolow, N=14). At W12, participants receiving placebos switched to respective frexalimab arms and entered the OLE. Key assessments during the OLE included safety and efficacy (number of Gd+ T1-lesions and new/enlarging T2-lesions).

Results:

125/129 (97%) participants completed the DBP and entered the OLE; 112 (87%) remained in the study at W48 cut-off. At W48, the number of Gd+ T1-lesions (mean [SD]) remained low in participants who continued receiving frexalimab and in those who switched from placebo to frexalimab at W12 (frexalimabhigh: 0.0 [0.2]; frexalimablow: 0.2 [0.5]; placebohigh/frexalimabhigh: 0.2 [0.6]; placebolow/frexalimablow: 0.1 [0.3]). Furthermore, 96% participants in frexalimabhigh, 87% in frexalimablow, 90% in placebohigh/frexalimabhigh, and 92% in placebolow/frexalimablow arms were free of Gd+ T1-lesions at W48. New/enlarging T2-lesion counts and T2-lesion volume change remained low with frexalimabhigh through W48, and lymphocyte counts were stable over 48 weeks. Overall, frexalimab treatment was well-tolerated through W48; the most common adverse events included nasopharyngitis, headache, and COVID-19.

Conclusions:

Frexalimab continued to show favorable safety and efficacy in RMS participants through W48. These data support its further development as a potential high-efficacy, non-lymphocyte-depleting treatment option in MS.

10.1212/WNL.0000000000205036