2026 American Academy of Neurology Abstract Website

Patrick Vermersch¹, Stephen Krieger², Heinz Wiendl³, Cristina Granziera⁴, Yang Mao-Draayer⁵, Gary Cutter⁶, Oleksandr Kalbus⁷, Ivan Staikov⁸, Michal Dufek⁹, Xavier Montalban¹⁰, Stephane Saubadu¹¹, Xiaodong Luo¹², Brendan Smyth¹², Biljana Djukic¹³, Philippe Truffinet¹¹, Erik Wallstroem¹³, Gavin Giovannoni¹⁴
¹University of Lille, Inserm U1172 LilNCog, CHU Lille, FHU Precise, Lille, France, ²Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ³Department of Neurology and Neurophysiology, University of Freiburg, Freiburg, Germany; Brain & Mind Institute, University of Sydney, Sydney, Australia, ⁴Translational 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, Basel, Switzerland, ⁵Autoimmunity Center of Excellence, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States, ⁶Department of Biostatistics, UAB School of Public Health, Birmingham, AL, United States, ⁷Department of Neurology, Dnipro State Medical University, Dnipro, Ukraine, ⁸Clinic of Neurology and Sleep Medicine, Acibadem City Clinic University Hospital Tokuda, Sofia, Bulgaria, ⁹First Department of Neurology, St. Anne’s University Hospital, Faculty of Medicine, Masaryk University, Brno, Czech Republic, ¹⁰Multiple Sclerosis Centre of Catalonia, Department of Neurology, Vall d'Hebron University Hospital, Barcelona, Spain, ¹¹Sanofi, Gentilly, France, ¹²Sanofi, Morristown, NJ, United States, ¹³Sanofi, Cambridge, MA, United States, ¹⁴Queen Mary University of London, London, United Kingdom

Objective:

To report efficacy and safety of frexalimab at Week (W)144 (3 years) in the phase 2 (NCT04879628) open-label extension (OLE) in participants with relapsing multiple sclerosis (pwRMS).

Background:

Frexalimab is a second-generation anti-CD40L monoclonal antibody that inhibits the costimulatory CD40/CD40L pathway and may recalibrate immune networks involving adaptive and innate immunity. During the double-blind period of the phase 2 trial, frexalimab was well-tolerated and showed 89% reduction in new gadolinium-enhancing (Gd+) T1-lesions with frexalimab-1200mg/intravenous (IV) vs placebo at W12.

Design/Methods:

129 participants were randomized (4:4:1:1) to frexalimab-1200mg/IV every 4 weeks (q4w) or frexalimab-300mg/subcutaneous (SC) q2w or matching placebo. After W12, 125 participants entered the OLE, during which placebo arm participants switched to the respective frexalimab arms. In the SC arms, the frexalimab dose was increased to 1800mg q4w to achieve pharmacokinetic comparability with the 1200mg q4w IV dose. By W112, all 57 SC participants switched to the 1800mg q4w dose, with W144 magnetic resonance imaging data available for 55 participants. Key endpoints included efficacy (number of Gd+ T1-lesions, new/enlarging T2-lesions, annualized relapse rate [ARR]) and safety outcomes.

Results:

As of June 24, 2025 (W144 cut-off), 100 participants (78%) remained on treatment. At W144, the total number of Gd+ T1-lesions (mean [SD]) remained low in all treatment groups (IV: 0.1 [0.3], placebo»IV: 0.3 [1.0]; SC: 0.0 [0.0] and placebo»SC: 0.1 [0.3]). New/enlarging T2-lesions monthly count also remained low through W144. Further, ARR (baseline–W144) was low in the original frexalimab-1200mg/IV arm, with 86% of participants remaining relapse-free. Frexalimab was well-tolerated through W144, with no new safety signals, stable lymphocyte counts and immunoglobulin levels.

Conclusions:

Frexalimab continues to exert sustained reduction in disease activity with favourable safety in pwRMS through 3 years, supporting its further development in phase 3 trials (FREXALT and FREVIVA) as a potential high-efficacy, non-lymphocyte-depleting therapy.