Data Regarding Novel CD40 Ligand Inhibitor as Potential Treatment for Individuals with Relapsing MS Presented at AAN 2025

Results from an open-label extension (OLE) of a phase 2 clinical trial (NCT04879628) for frexalimab (Sanofi; Bridgewater, NJ), an investigational CD40 ligand inhibitor not associated with lymphocyte depletion being studied as a potential treatment for people with relapsing multiple sclerosis, were presented at the American Academy of Neurology (AAN) 2025 Annual Meeting. By week 96, participants treated with frexalimab demonstrated sustained reductions in gadolinium-enhancing (Gd+) T1 lesions, low annualized relapse rates (ARRs), and a high rate of relapse-free status.

In the phase 2 study, 129 participants were randomized to receive either intravenous (IV) frexalimab 1200 mg every 4 weeks, subcutaneous (SC) frexalimab 300 mg every 2 weeks, SC placebo, or IV placebo. At the start of the OLE at week 12, participants who were randomized to receive placebo were switched to frexalimab (either SC or IV, depending on initial placebo administration method), and the SC dosage of frexalimab was increased to 1800 mg every 4 weeks. A total of 106 participants remained on treatment at the 96-week cutoff of the OLE.

• At 96 weeks, Gd+ T1 lesion count (mean [standard deviation]) was low for participants who were initially randomized to receive IV frexalimab (0.1[0.5]) and for those who switched from IV placebo to IV frexalimab (0.1[0.3]).
• At 96 weeks, Gd+ T1 lesion count also was low for participants initially randomized to SC frexalimab and for those who switched from SC placebo, with a mean of ≤0.4 across all SC groups.
• Participants who received IV frexalimab 1200 mg had a low monthly new/enlarging T2 lesion count.
• IV frexalimab–treated participants also showed a low ARR (0.08; 95% CI, 0.03 to 0.18); 92% of these individuals were relapse free.
• Nasopharyngitis, headache, and COVID-19 were the most common adverse events in the OLE.

Source: Vermersch P, Granziera C, Mao-Draayer Y, et al. Safety and efficacy of frexalimab from the phase 2 open-label extension in participants with relapsing multiple sclerosis: 2-year results. Presented at: American Academy of Neurology Annual Meeting; April 5–9, 2025; San Diego, CA.