PHOENIX — Frexalimab, a second-generation anti-CD40 ligand monoclonal antibody provides extended tight control of multiple sclerosis (MS) whether measured by relapse or brain imaging at 2-year follow-up, results of an open-label extension (OLE) of a phase 2 trial showed.
“At week 96, there was almost complete suppression of new gadolinium-enhancing lesions with very similar pattern seen with new or enhancing T2 lesions,” said study investigator Stephen Krieger, MD, professor of neurology, Icahn School of Medicine at Mount Sinai, New York City.
Two phase 3 international studies with this drug are already enrolling.
“Part of the interest in frexalimab and anti-CD40 therapies is the idea that one can modulate both B- and T-cell activity without cell depletion,” explained Krieger, who presented the long-term open-label data on May 29 at the Consortium of Multiple Sclerosis Centers (CMSC) 2025 Annual Meeting.
Near Complete Disease Suppression
The latest data suggest frexalimab is fulfilling its promise. Over follow-up to date, there has been nearly complete suppression of gadolinium-enhancing (Gd+) lesions on MRI among those taking the dose now being tested in the phase 3 trials. At 2 years, with an annualized relapse rate of 0.08%, 92% of patients were relapse-free.
The randomized portion of this phase 2 trial attracted attention when it was published a year ago in The New England Journal of Medicine, but the 2-year results showed that the efficacy and safety observed at 12 weeks persist.
In the controlled trial, 129 patients with relapsing MS were randomized to 300-mg, 400-mg, 600-mg, or 1200-mg frexalimab or matching placebos. Suppression of Gd+ lesions was the primary endpoint.
At 12 weeks, the adjusted mean of new Gd+ lesions was 1.4 in the combined placebo groups but 0.3 in the 300-mg frexalimab group and 0.2 in the 1200-mg group.
Of those who participated in the randomized portion of the phase 2 trial, 97% continued into the long-term OLE. The OLE consisted of two arms: 1200-mg frexalimab administered intravenously every 4 weeks