Sanofi has presented a broad range of new data underscoring its commitment to tackling both the clinical and scientific challenges of multiple sclerosis (MS).

The French company showcased results from 14 abstracts, spanning late-stage therapeutic trials, biomarker analyses, digital monitoring technologies, and studies into the economic burden of the disease. The data will be presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, which is taking place in Barcelona, Spain, from 24 to 26 September.

At the heart of Sanofi’s program were findings on tolebrutinib, its oral Bruton’s tyrosine kinase inhibitor (BTKi), and frexalimab, an investigational anti-CD40L antibody. The company also emphasized the importance of new tools to capture progression independent of relapses, along with data that highlight the high cost and unmet needs associated with progressive forms of MS.

Tolebrutinib: Slowing Disability Beyond Relapse Control

Tolebrutinib has been a focal point of Sanofi’s MS pipeline. The company acquired the drug as part of the $3.7 billion takeover of Principia Biopharma in 2021. Designed to cross the blood–brain barrier and act within the central nervous system, the therapy targets persistent immune activation thought to drive smouldering inflammation and long-term disability.

The drug is currently under priority review by the US Food and Drug Administration (FDA) for treating non-relapsing secondary progressive MS (nrSPMS) and to slow disability accumulation independent of relapse activity in adult patients, with the action date for the FDA decision set for 28 September 2025.

While the two Phase III GEMINI trials, GEMINI 1 (NCT04410978) and 2 (NCT04410991), in relapsing MS demonstrated that tolebrutinib did not outperform Sanofi’s other approved MS drug Aubagio (teriflunomide), in reducing relapses. New analyses showed that it did reduce the risk of disability worsening events that occurred independent of relapses. Nearly 80% of progression events in these studies were not linked to relapse activity, and patients receiving tolebrutinib experienced fewer of them compared with those on  Aubagio.

Further insights came from the Phase III HERCULES trial (NCT04411641) in nrSPMS, where tolebrutinib reduced the risk of confirmed disability progression by nearly a third compared to placebo. Subgroup analyses showed the effect was consistent across a wide range of patient characteristics, including age, sex, disability level, and MRI findings.

Supporting these clinical outcomes were detailed safety and biomarker findings. Over several years of treatment, immune cell counts, immunoglobulin levels, and platelet counts remained stable and within normal ranges. This suggests that the drug, while immunomodulatory, does not significantly deplete circulating immune cells, addressing one of the safety concerns common to many MS therapies.

Pharmacokinetic data reinforced the therapeutic potential, showing that higher plasma levels of tolebrutinib and its active metabolite were associated with greater protection against disability progression. Patient-reported outcomes added another dimension: while differences in quality-of-life scores were not evident early in treatment, by the two-year mark, patients receiving tolebrutinib reported improvements in both physical and mental health measures. Some benefits waned later, but when averaged across the study, quality-of-life outcomes generally favored tolebrutinib.

Mechanistic work further suggested that the therapy induces complex shifts in immune regulation. Although total counts of B and T cells remained unchanged, researchers observed changes in differentiation patterns of B-cell subsets and helper T cells, along with reductions in inflammatory monocyte populations. These shifts may help explain tolebrutinib’s ability to slow progression in progressive MS without broad immune suppression.

Frexalimab: Targeting CD40L to Modulate Inflammation

In addition to tolebrutinib, Sanofi presented preclinical and clinical findings on frexalimab, its investigational anti-CD40L antibody. CD40L plays a central role in activating both innate and adaptive immune responses, and blocking this pathway could help modulate chronic inflammation without depleting immune cells.

In a progressive MS animal model, treatment with an anti-CD40L antibody reduced the severity of disease, improved clinical outcomes, and lessened neuroinflammation. The therapy appeared to reduce infiltration of inflammatory T cells into the central nervous system and dampen production of key inflammatory cytokines. These results provide biological support for frexalimab’s ongoing Phase III evaluation in both relapsing and progressive forms of MS.

Beyond Drugs: Tools to Track and Measure Progression

Sanofi also highlighted research designed to address gaps in how MS is measured and understood.

One study examined the clinical and economic burden of secondary progressive MS in the United States, drawing on insurance claims from more than 5,000 patients. Compared with matched controls, people with SPMS faced higher rates of comorbidities, hospitalizations, emergency visits, and reliance on rehabilitation therapies. Healthcare costs were nearly eight times higher, with patients incurring an average of more than $160,000 over two years. The findings illustrate the high burden faced by patients and the healthcare system alike, reinforcing the urgency of developing effective therapies for progressive MS.

Another effort focused on developing more sensitive measures of disability progression. The Smouldering Associated Worsening (SAW) index aims to capture subtle changes that occur even in the absence of relapses. Baseline data from 40 patients showed that difficulties with walking, cognition, fatigue, and balance were the most commonly reported signs of worsening. By grounding the index in patient experience, researchers hope to create a more reliable tool for monitoring progression outside of traditional relapse-driven metrics.

Digital tools were also on display. Interim results from the ongoing MS-DETECT study (NCT05816122) evaluated MSCopilot, a smartphone-based application designed to measure walking, dexterity, cognition, and vision from home. Results showed strong correlations between the digital measures and established clinical tests, with high patient adherence and data quality. If validated further, such digital biomarkers could enable earlier detection of disease worsening and more continuous monitoring, reducing reliance on clinic-based assessments.

A Comprehensive Approach to MS

The breadth of Sanofi’s ECTRIMS program highlights a multi-layered strategy. On one hand, the company is advancing late-stage therapies such as tolebrutinib, which has already demonstrated consistent benefits in both relapsing and progressive forms of MS. On the other, it is investing in innovative approaches like frexalimab, which targets a novel pathway with the potential for high efficacy and a distinct safety profile.

At the same time, Sanofi is contributing to efforts that go beyond drug development, from real-world economic analyses to new clinical and digital tools. Together, these initiatives reflect a shift in MS research toward tackling the disease on multiple fronts: slowing disability, enhancing quality of life, and better detecting subtle changes that often precede significant decline.

Tolebrutinib is currently under regulatory review in several markets, including the United States, where it has been granted Breakthrough Therapy Designation for nrSPMS. Frexalimab remains under investigation for multiple diseases, with two Phase III studies in RMS (NCT06141473) and nrSPMS (NCT06141486), and Phase II studies in systemic lupus erythematosus (NCT05039840), Type 1 diabetes (NCT06111586), and focal segmental glomeruloscelerosis (NCT06500702).

The broader challenge will be integrating new therapies with emerging biomarkers and digital tools to create a more personalized, proactive model of MS care. As Sanofi’s data at ECTRIMS demonstrate, the field is moving toward a future in which slowing progression and detecting early worsening are just as important as preventing relapses.