CMSC 2026: Trial data show frexalimab benefits lasting 3 years
Patients with relapsing disease show stable disability levels
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Medication is administered through an IV infusion. (Photo by iStock)
Three years of treatment with Sanofi’s investigational antibody therapy frexalimab was associated with persistently low disease activity and no new safety concerns in people with relapsing forms of multiple sclerosis (MS).
That’s according to new data from an ongoing open-label extension phase of a global Phase 2 clinical trial (NCT04879628), which showed that brain lesions and relapse rates have stayed low, while disability levels have remained stable.
Stephen Krieger, MD, neurology professor at the Icahn School of Medicine at Mount Sinai, presented the findings at the Consortium of MS Centers (CMSC) annual meeting, held last week in Charlotte, North Carolina.
“Things are really quite stable and assuring for frexalimab out to three years,” Krieger said in the talk, titled, “Efficacy and Safety of Frexalimab In Participants with Relapsing Multiple Sclerosis: 3-Year Results from the Phase 2 Open-Label Extension.”
“There is a sustained reduction in disease activity,” Krieger said. The treatment is “a very well-tolerated monthly simple infusion, and there have not been emerging safety signals,” he said.
Treatment aims to reduce harmful responses, maintain immune function
Frexalimab is designed to block the CD40/CD40L signaling pathway, which plays a key role in activating immune cells that drive disease-related inflammation.
Unlike many approved MS therapies, the therapy is intended to reduce harmful immune responses without depleting immune cells or preventing them from circulating normally throughout the body to fight infections.
“The goal … is to be able to create this sort of efficacy without some of the consequences of immune suppression that can occur in cell-depleting mechanisms,” Krieger said.
The proof-of-concept Phase 2 trial enrolled 129 adults with relapsing forms of MS, who were randomly assigned to receive either frexalimab or a placebo for 12 weeks (about three months). Among those given frexalimab, some received monthly into-the-vein (intravenous) infusions (1,200 mg), while others were given under-the-skin (subcutaneous) injections (300 mg) every two weeks.
Results showed that intravenous frexalimab significantly reduced the number of new lesions with active inflammation, by 89%, compared with a placebo after three months, meeting the study’s main goal. The under-the-skin formulation was similarly associated with a significant reduction, by 79%, compared with the placebo.
After the main study, participants could enter an ongoing open-label extension portion in which all are receiving intravenous or subcutaneous frexalimab. In this part, the subcutaneous dose was increased to 1,800 mg monthly to achieve a drug exposure that better matches the intravenous regimen.
Data presented last year showed that lesion counts and relapse rates remained low for up to 2.5 years on frexalimab. Krieger gave a three-year update at the CMSC meeting, showing that the mean number of lesions with active inflammation remained “incredibly low.” The same was true for new and enlarging lesions, and total lesion volume remained overall stable throughout the years.
Relapse activity also remained low. Among participants who had received intravenous frexalimab from the start of the study, 86% remained relapse-free through year three, with a mean of 0.11 relapses per year.
Disability scores, measured using the Expanded Disability Status Scale (EDSS), also remained stable over time.
Data presented at the meeting also showed that levels of immune lymphocytes and antibodies remained stable through year three, supporting the idea that the therapy does not work by depleting immune cells. No new safety signals were observed.
“In some ways, this is the most important part,” Krieger said. “It’s always important to make sure that efficacy is maintained, but what we’re really looking for in a long-term study is evidence of negative consequences, adverse events, or a risk profile that could evolve over time.”
Phase 3 trials continue
Three ongoing Phase 3 trials are now evaluating frexalimab in larger groups of MS patients. The twin FREXALT trials (NCT06141473) are comparing frexalimab with the approved oral therapy Aubagio (teriflunomide) in people with relapsing forms of MS, while FREVIVA (NCT06141486) is comparing frexalimab with a placebo in people with nonrelapsing secondary progressive MS (SPMS).
“We are hoping this continues to be a high-efficacy strategy for … both relapsing and progressive [MS],” Krieger said.
The FREXALT and FREVIVA trials are testing the intravenous formulation of frexalimab. Sanofi is still working on the subcutaneous version.
In a poster presented at the meeting, “Subcutaneous Administration of Frexalimab in Relapsing Multiple Sclerosis and Nonrelapsing Secondary Progressive Multiple Sclerosis: Design of the Phase 3 Frexcite Trial,” researchers described the design of the Phase 3 FREXCITE trial (NCT07325292), which is testing whether the subcutaneous formulation works similarly to the intravenous version.
About 160 people with relapsing MS or nonrelapsing SPMS will receive monthly frexalimab, either subcutaneously (1,800 mg) or intravenously (1,200 mg) for about six months, after which all will be switched to subcutaneous dosing.
Subcutaneous doses will be self-administered using single-use, wearable injection devices placed on the abdomen. These injections take six to 30 minutes, while intravenous infusions take about an hour.
The main goal is to demonstrate that subcutaneous dosing is just as good as intravenous dosing for achieving therapeutic levels of the medication in the bloodstream. Other pharmacological and safety properties will also be evaluated, along with patient preferences and other patient-reported outcome measures.
Note: The Multiple Sclerosis News Today team is providing live coverage of the Consortium of MS Centers Annual Meeting, May 27-29. Go here to see the latest stories from the meeting.
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