New Phase II Data Shows Frexalimab Reduced Nerve Cell Damage in Relapsing Multiple Sclerosis

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Emerging data released from Sanofi show its CD40L monoclonal antibody, frexalimab, reduced a key biomarker associated with multiple sclerosis (MS) nerve cell damage in patients with relapsing MS. These new Phase II trial results showed significant reduction in plasma levels of neurofilament light chain (NfL) after one year of treatment, a biomarker of nerve cell damage that is typically elevated in people living with MS.¹

The Phase II clinical trial was a randomized, double-blind, placebo-controlled study. Participants were randomized to receive either 1200 mg of frexalimab intravenously every four weeks, with an initial 1800 mg loading dose, or 300 mg subcutaneously every two weeks, with an initial 600 mg loading dose or matching placebo for 12 weeks (part A). The primary endpoint was the reduction in the number of new Gd+ T1 MRI brain lesions at week 12. Secondary endpoints included additional MRI-based efficacy measures as well as the safety, tolerability, and pharmacokinetics of frexalimab. After week 12, participants receiving placebo switched to respective frexalimab arms and entered the open-label part B.

“As our science and diagnostic tools have evolved, so has our understanding of multiple sclerosis. We now know that NfL levels may be related to both acute inflammatory damage and chronic diffuse neuronal loss leading to disability progression, strengthening its position as a key biomarker of nerve cell damage in people with multiple sclerosis,” Patrick Vermersch, MD, PhD, University of Lille, CHU Lille, France said in a press release. “These data presented at EAN (10th Congress of the European Academy of Neurology) suggest that CD40L inhibition may reduce nerve cell damage in people with multiple sclerosis and reinforce the potential of frexalimab to slow or halt disease progression for people living with this disease.”

According to Sanofi, 97% of the study participants from the initial 12-week double-blind period entered the open-label extension (OLE) of the Phase II study, and 87% remained in the study by the 48-week cut-off. During the OLE, treatment groups consisted of participants with relapsing MS receiving either high-dose frexalimab regimens, low-dose frexalimab regimens, or placebo-matched groups that switched to matching high or low doses of frexalimab at week 12 (placebo-low/frexalimab-low and placebo-high/frexalimab-high). Plasma NfL samples were collected and analyzed from all four groups at baseline, week 12, week 24, and week 48.

Recent findings from the National MS Society show there are an estimated 1 million people in the United States living with MS, which is double the last reported number in 1975.²

“People with multiple sclerosis need new high-efficacy treatment options that target disability progression, which remains an unmet need. These results, alongside the previously reported Phase II efficacy and safety results, further show that frexalimab’s novel mechanism of action has the potential to deliver meaningful improvements for people living with this chronic and debilitating disease,” Erik Wallström, MD, PhD, global head of neurology development, Sanofi added in the press release.

Additionally, Sanofi has two global Phase III studies of frexalimab in relapsing MS (NCT06141473) and non-relapsing secondary progressive MS (NCT06141486) underway.

References

1. Media Update: Frexalimab new phase 2 data showed reduction of key biomarker of nerve cell damage in relapsing MS. News release. Sanofi. June 28, 2024. Accessed July 1, 2024. https://www.sanofi.com/en/media-room/press-releases/2024/2024-06-28-15-30-00-2906026.

2. Healthline. Multiple Sclerosis: Facts, Statistics, and You. Retrieved from https://www.healthline.com/health/multiple-sclerosis/facts-statistics-infographic