Favorable Outcomes Reported for Novel Therapy Frexalimab in Reducing Disease Activity in Those with Relapsing Multiple Sclerosis

Frexalimab (SAR441344; Sanofi, Bridgewater, NJ), an investigational anti-CD40L monoclonal antibody, was shown to reduce disease activity in individuals with relapsing multiple sclerosis (RMS) according to study results published in The New England Journal of Medicine. Inhibition of CD40L with frexalimab treatment reduced the number of new gadolinium-enhancing T1-weighted lesions with only minor safety events reported.

The phase 2, double-blind, randomized, placebo-controlled trial (NCT04879628) took place over 12 weeks and included 125 participants with RMS who were assigned to receive either 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800 mg loading dose, n=50), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose, n=49), or the matching placebos for each active treatment (n=12 for intravenous placebo, n=14 for subcutaneous placebo). The primary end point for this study was the number of new gadolinium-enhancing T1-weighted lesions seen on MRI at week 12 relative to week 8.

• The adjusted mean number of new gadolinium-enhancing T1-weighted lesions at week 12 relative to week 8 was 0.2 (95% 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.
• At week 12, a total of 85% of the participants who received 1200 mg of frexalimab intravenously and 84% of those who received 300 mg frexalimab subcutaneously had no new gadolinium-enhancing lesions, as compared with 50% of the participants in the pooled placebo group.

“Frexalimab has a unique mechanism of action, blocking the CD40/CD40L costimulatory pathway thought to regulate both adaptive and innate immune cell activation and function–a pathway that is pivotal in the pathogenesis of MS,” said study author and Chair of Neurology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Dr. Gavin Giovannoni. “We are thrilled with the results achieved with frexalimab in just 3 months, which shows that CD40L inhibition rapidly controls MS disease activity without lymphocyte depletion.”

Study limitations include the short trial period and small sample size. Sanofi supported this study and has initiated 2 phase 3 trials to study frexalimab treatment in participants with relapsing and progressive multiple sclerosis.