AAN 2025: Frexalimab results promising over 2-year extension
Sanofi drug maintains disease control, slows progression in RRMS participants
Frexalimab, an experimental antibody-based medication, was well tolerated and maintained disease control over two years in adults with relapsing forms of multiple sclerosis (MS).
That’s according to new data from an open-label extension to a Phase 2 clinical trial (NCT04879628) in which frexalimab outperformed a placebo at reducing the number of active and new or enlarging brain lesions in adults with relapsing-remitting MS or active secondary progressive MS (SPMS) after 12 weeks.
Two-year data now show that patients who received a high frexalimab dose in the main trial and the extension continued to have a low number of active and new or enlarging brain lesions, alongside stable disability levels. Most also remained relapse-free for the whole two years.
The findings were presented by Patrick Vermersch, MD, PhD, a neurologist at the Hospital Center University of Lille, France, at the American Academy of Neurology (AAN) 2025 Annual Meeting, held April 5-9 in San Diego and online. His presentation was titled “Safety and Efficacy of Frexalimab from the Phase 2 Open-label Extension in Participants with Relapsing Multiple Sclerosis: 2-year Results.”
“Frexalimab continues to show favorable safety and sustained reduction in disease activity,” the researchers wrote.
These data support ongoing Phase 3 clinical testing of frexalimab in FREXALT (NCT06141473), which is enrolling about 1,400 adults with relapsing forms of MS, and FREVIVA (NCT06141486), which is seeking about 900 adults with nonrelapsing SPMS. Both clinical trials are sponsored by Sanofi, which is developing frexalimab.
The study and its results
Frexalimab is a second-generation antibody designed to inhibit the CD40/CD40L pathway, which plays a key role in activating immune cells in the body. It is expected to control both new and ongoing inflammation in MS without reducing the number of circulating white blood cells or causing blood clots, a serious side effect of earlier CD40L inhibitors.
The Phase 2 clinical trial included 129 adults with relapsing forms of MS who were randomly assigned to one of two doses of frexalimab — 1,200 mg administered monthly into the vein or 300 mg given every other week via an under the skin injection — or a placebo for 12 weeks.
After this period, the high-dose group had 89% fewer brain lesions with active inflammation than the placebo, and the low-dose group had a 79% reduction in those lesions. The total number of new and enlarging lesions was also reduced with both doses.
Following the main trial, 97% of participants chose to join an open-label extension, in which all received frexalimab for up to 96 weeks (almost two years). Those who had initially received a placebo were given a high or low frexalimab dose, while those already on the experimental therapy continued on their assigned dose.
Later, the under-the-skin dose was increased to 1,800 mg every four weeks to match the exposure to frexalimab in the into-the-vein group.
By week 96, 106 patients were still receiving treatment with frexalimab. Results showed that the number of brain lesions with active inflammation remained low in all groups, including those who had switched from a placebo to frexalimab. The monthly count of new or enlarging brain lesions and the total lesion volume were also low.
Relapse rates were also low in all groups, though the greatest benefits were seen in patients who were given the high dose in the main and extension trial periods. In this group, patients experienced a rate of 0.08 relapses per year, and most (92%) remained relapse-free.
Finally, disability scores on the Expanded Disability Status Scale (EDSS) similarly “remained low and stable in all groups,” Vermersch said, indicating the antibody may be able to slow the progression of disability in these patients.
Frexalimab was well tolerated over the two years, with the most common side effect reported during the study being the common cold, headache, and COVID-19. One patient experienced a pulmonary embolism that could be consistent with an effect of frexalimab on blood clots, but researchers believe there’s a “high probability” of it not being related to the drug.
“Frexalimab treatment led to a sustained reduction of disease activity over two years,” as evidenced by a very low number of active and new or enlarging lesions in MRI scans, Vermersch concluded, adding that clinical endpoints also remained stable during the extension period.
This result supports the drug’s “further development in Phase 3 trials as a potential high-efficacy … therapy,” he wrote in his presentation.
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