Frexalimab linked to reduction in lesion activity, well tolerated in relapsing MS

Key takeaways:

• A phase 2 study included 129 individuals with MS randomized to receive frexalimab or placebo for 24 weeks.
• Reduction in T1 and T2 lesions was more significant in the high dose frexalimab group.

In a cohort of individuals with relapsing multiple sclerosis, treatment with frexalimab significantly reduced new MRI lesions by week 24, according to a data presented at ECTRIMS 2023.

“Frexalimab, the first second-generation anti-CD40L monoclonal antibody to be studied in [multiple sclerosis], may modify T- and B-cell activation and innate immune cell function, reducing inflammation without lymphocyte depletion,” Patrick Vermersch, MD, PhD, a neurologist at the University of Lille in France, and colleagues wrote.

Vermersch and fellow researchers aimed to present safety and efficacy data at week 24 from the ongoing open-label extension study stemming from a phase 2 clinical trial of frexalimab (Sanofi) for those with relapsing MS.

Their analysis included 129 participants aged 18 to 55 years who were randomized on a 4:4:1:1 basis to receive high-dose frexalimab (n = 52), low-dose frexalimab (n = 51), or matching placebos (high dose, n = 12; low dose, n = 14). At week 12, those receiving placebo were switched to corresponding frexalimab arms and entered the open-label portion. Primary assessments included safety and efficacy with respect to the number of new Gadolinium T1 (Gd+ T1) lesions as well as new/enlarging T2 lesions. A total of 125 enrollees entered the open label extension phase.

At week 24, 96% of participants in the continuing high-dose frexalimab arm recorded no instances of new Gd+ T1 lesions while 91% recorded no new/enlarging T2 lesions.

In the low-dose frexalimab arm, new Gd+ T1 lesion count was 0.5 (0.17) by week 12 and 0.3 (0.12) at week 24; 80% of participants had no new Gd+ T1 lesions and 74% participants had no new/enlarging T2 lesions.

Among placebo-switch participants, Vermersch and colleagues observed the monthly count of new Gd+ T1 lesions decreased from 2.3 (1.49) at week 12 to 0.4 (0.31) at week 24 in the high-dose frexalimab arm and 3.7 (2.31) at week 12 to 0.6 (0.44) at week 24 in the low-dose frexalimab arm.

Data additionally showed no new safety concerns, with the most common adverse events (10% in any group) being mild to moderate cases of COVID-19, nasopharyngitis and headache.

“These findings provide proof of concept for targeting CD40L in MS and support development of frexalimab as a potential high-efficacy, non-depleting, MS therapy,” Vermersch and colleagues wrote.