Sanofi’s innovative second-generation investigational anti-CD40L antibody, Frexalimab, has astounded experts in the field by significantly reducing disease activity in patients with relapsing multiple sclerosis (MS). In a Phase 2 trial, patients on the higher-dose treatment saw a reduction of 89%, and those on the lower-dose reduced by 79%, in the number of new gadolinium-enhancing (GdE) T1-lesions after 12 weeks of therapy.
This news, presented at the upcoming 2023 Consortium of Multiple Sclerosis Centers (CMSC) annual meeting, has given scientists hope that Frexalimab’s unique mechanism of action could offer a promising new treatment for this challenging condition.
Frexalimab is revolutionising the treatment of multiple sclerosis (MS) with its unprecedented ability to inhibit the CD40/CD40L pathway – essential for adaptive and innate immune cell activation – without depleting lymphocyte counts.
Promising to provide sustained control of the disease, as well as reduce disability progression, frexalimab is setting a new standard in MS care, tackling the unmet need for an effective, safe therapeutic option.
Erik Wallström, MD, PhD
For the past two decades, we have been dedicated to researching and developing new therapies for multiple sclerosis. Now, we are determined to build upon this hard work by finding innovative treatments that may have the capacity to stop the progression of disability in MS patients, which unfortunately remains a large unresolved medical need. With various approaches and unique modes of action, our ongoing exploration into this pressing issue is highly-prized and carried out with great enthusiasm.
Gavin Giovannoni, MD, PhD, FCP, FRCP, FRCPath
Frexalimab has been exhilaratingly successful in controlling MS symptoms within just three months by targeting the CD40/CD40L costimulatory pathway, which is believed to be an integral part of the disease pathogenesis.
This innovative mechanism of action blocks the pathway to inhibit the activation and function of both the adaptive and innate immune cells. A rapid and meaningful response to the treatment is now possible due to the power of this new approach.
About the Phase 2 study
In Phase 2 of the clinical trial, 129 patients with relapsing MS were randomly assigned to receive either a higher (n=52) or lower dose (n=51) of frexalimab, or a placebo (n=12 + n=14; pooled for efficacy analyses), for a 12-week period (Part A). After Week 12, those taking placebo switched to respective frexalimab arms and progressed to the open-label Part B.
Primary endpoint assessed was the reduction in the number of new GdE T1-hyperintense brain lesions, but secondary endpoints also included other MRI-based efficacy measures, as well as the safety, tolerability, and pharmacokinetics of frexalimab. The study is ongoing.
The incredible effects of frexalimab have been observed in a recent study, with both high- and low-dose treatments leading to significant reductions in new GdE T1-hyperintense lesions after 12 weeks. Specifically, treatment with frexalimab saw reductions of 89% and 79% for high- and low-doses respectively, in comparison to the placebo group.
Furthermore, the 24-week mark saw 96% of participants within the higher-dose frexalimab arm completely free of further new GdE T1-lesions. Other effects – such as early effects on patient-reported MSIS-29 physical impact score and NfL plasma levels – are also being reported.
Frexalimab was proven to be effective and safe for 125 (97%) patients from the Part A study including those who continued in the open-label Part B. The most commonly reported adverse events such as COVID-19 and headache occurred in the lower-dose group (9.8% of cases) and higher-dose group (5.8% of cases) respectively. All cases of COVID-19 reported were mild to moderate in severity and can be easily managed.
Sanofi is developing a revolutionary monoclonal antibody, Frexalimab (SAR441344) under an exclusive licensing agreement with ImmuNext Inc. Though yet to be reviewed by regulatory authorities, Frexalimab looks to be a promising option when it comes to immune defense since it is believed to block the costimulatory CD40/CD40L cellular pathway without lymphocyte-depletion for both adaptive (T and B cells) and innate (macrophages and dendritic cells) immunity.
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