Positive Phase 2 data of novel investigational anti-CD40L antibody frexalimab show significantly reduced disease activity in relapsing multiple sclerosis

• Frexalimab met primary endpoint with 89% reduction in new gadolinium-enhancing T1 brain lesions achieved at Week 12 in the higher-dose treatment arm, compared with placebo
• Sanofi plans to initiate pivotal trials in multiple sclerosis in early 2024

Paris, May 31 2023. New data, being presented in a late-breaking session at the 2023 Consortium of Multiple Sclerosis Centers (CMSC) annual meeting, demonstrate that frexalimab, Sanofi’s novel second-generation investigational anti-CD40L antibody, with a unique mechanism of action, significantly reduced disease activity in a Phase 2 trial of patients with relapsing multiple sclerosis (MS). Following 12 weeks of therapy, the number of new gadolinium-enhancing (GdE) T1-lesions was reduced by 89% and 79% in the higher- and lower-dose treatment arms, respectively, compared with placebo, meeting the study’s primary endpoint.

A substantial unmet need remains in MS for highly effective and well-tolerated treatment options that provide sustainable control of disease activity and disability progression, while minimizing risks. As the first second-generation anti-CD40L antibody to show efficacy in MS, frexalimab is thought to block the costimulatory CD40/CD40L cellular pathway necessary for adaptive (T and B cells) and innate (macrophages and dendritic cells) immune cell activation and function, without lymphocyte-depletion.

Erik Wallström, MD, PhD
Global Head of Neurology Development, Sanofi
"Building on our 20 years of research and development in multiple sclerosis, we are committed to growing our robust pipeline of MS therapies by exploring multiple treatment approaches with unique MOAs that have the potential to slow or halt disability, which remains one of the greatest unmet medical needs in multiple sclerosis today.”

Gavin Giovannoni, MD, PhD, FCP, FRCP, FRCPath
Chair of Neurology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London
"Frexalimab has a unique mechanism of action, blocking the CD40/CD40L costimulatory pathway thought to regulate both adaptive and innate immune cell activation and function – a pathway that is pivotal in the pathogenesis of MS. We are thrilled with the results achieved with frexalimab in just 3 months, which shows that CD40L inhibition rapidly controls MS disease activity without lymphocyte depletion.”

Pivotal trials in MS are planned to be launched in 2024.

About the Phase 2 study
The Phase 2 study was a randomized, double-blind, placebo-controlled trial evaluating frexalimab in patients with relapsing MS. In the trial, 129 patients with relapsing MS were randomized (4:4:1:1) to receive either higher or lower doses of frexalimab (n=52 and n=51, respectively) or matching placebo (n=12 and n=14, respectively; pooled for efficacy analyses) for 12 weeks (Part A). After Week 12, patients receiving placebo switched to respective frexalimab arms and entered the open-label Part B, which is currently ongoing. The primary endpoint was the reduction in the number of new GdE T1-hyperintense MRI brain lesions after 12 weeks of treatment. Secondary endpoints included additional MRI-based efficacy measures as well as the safety, tolerability and pharmacokinetics of frexalimab.

In the study, both groups receiving higher or lower doses of frexalimab had significant reductions in new GdE T1-hyperintense lesions after 12 weeks of treatment. At Week 12, high- and low-dose frexalimab significantly reduced the number of new GdE T1-lesions by 89% (95%CI: 62%-97%, p=0.0004) and 79% (95%CI: 44%-92%, p=0.0021), respectively, versus placebo (pooled dose groups). Additionally, both groups treated with frexalimab showed reductions in new or enlarging T2-lesions and total GdE T1-lesions. At Week 24, 96% of participants in the higher-dose frexalimab arm were free of new GdE T1-lesions. Early effects (Week 12) on MSIS-29 physical impact score (a patient-reported outcome) and plasma neurofilament light chain (NfL) levels will also be reported.

Frexalimab was well-tolerated, and 125 (97%) patients completed Part A and continued to the open-label Part B. The most common adverse events (≥4%) in any frexalimab-treated group were COVID-19 (n=5 [9.8%] in the lower-dose group; all uncomplicated cases of mild or moderate intensity) and headache (n=1 [2.0%] and n=3 [5.8%] in the lower- and higher-dose group, respectively).

About frexalimab
Frexalimab (SAR441344) is a novel monoclonal antibody that is thought to block the costimulatory CD40/CD40L cellular pathway necessary for adaptive (T and B cells) and innate (macrophages and dendritic cells) immune cell activation and function, without lymphocyte-depletion. Sanofi is developing SAR441344 under an exclusive license from ImmuNext Inc. Frexalimab is an investigational product, and its safety and efficacy has not been reviewed by any regulatory authority.

About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.

Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY

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