Title :

Inhibition of CD40L with Frexalimab in Multiple Sclerosis

Author(s) :

Vermersch, Patrick [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Granziera, Cristina [Auteur]
University Hospital Basel [Basel]
Université de Bâle = University of Basel = Basel Universität [Unibas]
Mao-Draayer, Yang [Auteur]
Université du Michigan = University of Michigan [Ann Arbor] [UMich]
Cutter, Gary [Auteur]
University of Alabama [Birmingham] [UAB]
Kalbus, Oleksandr [Auteur]
Dnipropetrovsk National University [DNU]
Staikov, Ivan [Auteur]
Dufek, Michal [Auteur]
St. Anne’s University Hospital [Brno]
Saubadu, Stephane [Auteur]
Sanofi Aventis R&D [Chilly-Mazarin]
Bejuit, Raphael [Auteur]
Sanofi Aventis R&D [Chilly-Mazarin]
Truffinet, Philippe [Auteur]
Sanofi Aventis R&D [Chilly-Mazarin]
Djukic, Biljana [Auteur]
Wallstroem, Erik [Auteur]
Giovannoni, Gavin [Auteur]
Queen Mary University of London [QMUL]

Journal title :

New England Journal of Medicine

Abbreviated title :

N Engl J Med

Volume number :

390

Pages :

589-600

Publisher :

Massachusetts Medical Society

Publication date :

2024-02-15

ISSN :

1533-4406

English keyword(s) :

Allergy/Immunology General
Autoimmune Disease
Inflammatory Disease
Multiple Sclerosis
T-Cells

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Background : The CD40–CD40L costimulatory pathway regulates adaptive and innate immune responses and has been implicated in the pathogenesis of multiple sclerosis. Frexalimab is a second-generation anti-CD40L monoclonal ...
Show more >Background : The CD40–CD40L costimulatory pathway regulates adaptive and innate immune responses and has been implicated in the pathogenesis of multiple sclerosis. Frexalimab is a second-generation anti-CD40L monoclonal antibody being evaluated for the treatment of multiple sclerosis. Methods : In this phase 2, double-blind, randomized trial, we assigned, in a 4:4:1:1 ratio, participants with relapsing multiple sclerosis to receive 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose), or the matching placebos for each active treatment. The primary end point was the number of new gadolinium-enhancing T1-weighted lesions seen on magnetic resonance imaging at week 12 relative to week 8. Secondary end points included the number of new or enlarging T2-weighted lesions at week 12 relative to week 8, the total number of gadolinium-enhancing T1-weighted lesions at week 12, and safety. After 12 weeks, all the participants could receive open-label frexalimab. Results : Of 166 participants screened, 129 were assigned to a trial group; 125 participants (97%) completed the 12-week double-blind period. The mean age of the participants was 36.6 years, 66% were women, and 30% had gadolinium-enhancing lesions at baseline. At week 12, the adjusted mean number of new gadolinium-enhancing T1-weighted lesions was 0.2 (95% confidence interval [CI], 0.1 to 0.4) in the group that received 1200 mg of frexalimab intravenously and 0.3 (95% CI, 0.1 to 0.6) in the group that received 300 mg of frexalimab subcutaneously, as compared with 1.4 (95% CI, 0.6 to 3.0) in the pooled placebo group. The rate ratios as compared with placebo were 0.11 (95% CI, 0.03 to 0.38) in the 1200-mg group and 0.21 (95% CI, 0.08 to 0.56) in the 300-mg group. Results for the secondary imaging end points were generally in the same direction as those for the primary analysis. The most common adverse events were coronavirus disease 2019 and headaches. Conclusions : In a phase 2 trial involving participants with multiple sclerosis, inhibition of CD40L with frexalimab had an effect that generally favored a greater reduction in the number of new gadolinium-enhancing T1-weighted lesions at week 12 as compared with placebo. Larger and longer trials are needed to determine the long-term efficacy and safety of frexalimab in persons with multiple sclerosis. (Funded by Sanofi; ClinicalTrials.gov number, NCT04879628.)Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Research team(s) :

Neuroinflammation & Multiple Sclerosis (NEMESIS)

Submission date :

2024-02-17T22:04:21Z
2025-02-21T15:53:33Z