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The following is a summary of “Inhibition of CD40L with Frexalimab in Multiple Sclerosis,” published in the February 2024 issue of Neurology by Vermersch et al.
Researchers conducted a retrospective study investigating the potential of frexalimab, a second-generation anti-CD40L antibody, in modulating the CD40-CD40L pathway for multiple sclerosis (MS) treatment.
They conducted a phase 2 trial, where participants with relapsing MS were randomly assigned in a 4:4:1:1 ratio to receive either 1200 mg of intravenous frexalimab every 4 weeks (including an 1800-mg loading dose), 300 mg of subcutaneous frexalimab every 2 weeks (with a 600-mg loading dose), or corresponding placebos. The primary goal was to assess the number of new gadolinium-enhancing T1-weighted lesions on week 12 compared to week 8 on magnetic resonance imaging. Secondary objectives comprised assessing new or enlarging T2-weighted lesions from week 8 to week 12, total gadolinium-enhancing T1-weighted lesions at week 12, and safety measures. After 12 weeks, all participants were eligible for open-label frexalimab treatment.
The results showed 166 screened participants; 129 were assigned to a trial group; 125 (97%) completed the 12-week double-blind period with a mean age of 36.6 years, with 66% being women and 30% showing gadolinium-enhancing lesions at baseline. At week 12, the adjusted mean number of new gadolinium-enhancing T1-weighted lesions was 0.2 (95% CI, 0.1 to 0.4) in the 1200 mg intravenous frexalimab group and 0.3 (95% CI, 0.1 to 0.6) in the 300 mg subcutaneous frexalimab group, compared to 1.4 (95% CI, 0.6 to 3.0) in the pooled placebo group. The rate ratios relative to 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. Secondary imaging endpoint results were generally aligned with the primary analysis. The prevalent adverse events included COVID-19 and headaches.
They concluded that the phase 2 trial suggests frexalimab reduced brain lesions in MS patients, though further studies are needed.
Source: nejm.org/doi/full/10.1056/NEJMoa2309439
