Nasal administration of foralumab, a fully human anti-CD3 monoclonal antibody, showed positive clinical effects for 2 patients with nonactive secondary progressive multiple sclerosis (SPMS), according to findings presented at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis.

After at least 3 months of treatment, both patients had reductions in microglial activation, lower levels of proinflammatory cytokines, and positive effects on clinical scores. At the time of reporting, no adverse reactions, local irritation, or laboratory abnormalities had been observed.

One of the patients, EA1, who had completed 6 months of treatment, subjectively reported feeling more stable and having more strength in his lower extremities. Stabilization or improvement in Expanded Disability Status Scale scores, pyramidal motor scores, and timed 25-foot walk tests were observed during the study. Nine-Hole Peg test and Symbol Digit Modalities test scores were also stable during treatment.


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Significant reduction in serum protein cytokine levels including interferon gamma, interleukin-18, interleukin-1-beta, and interleukin-6 were observed through the Olink assay. An increase in CD8 naïve cells and a decrease in CD8 effector cells were both shown in cellular immune studies. Alterations in gene expression were also found through single-cell RNA sequencing.

Previous studies of intranasal foralumab in a chronic experimental autoimmune encephalomyelitis model showed a reduction in microglia and astrocyte inflammation. In human controls dosed at 10 μg, 50 μg, and 250 μg for 5 days, treatment was found to be safe and immune effects were seen at 50 μg. Nasal foralumab was also tested in patients with COVID-19 for 10 days and was found to be “well-tolerated and exhibited positive effects on blood markers and lung inflammation,” the authors noted.

The 2 patients recruited for the study had nonactive SPMS with sustained clinical progression despite the use of approved disease-modifying therapies, including ocrelizumab for 3 years most recently. EA1 is a 61-year-old male and was diagnosed for over 20 years ago with MS, while EA2 is a 42-year-old male, who was diagnosed 8 years ago.

Both patients received nasal foralumab at 50 μg/day in 3-week cycles of 2 weeks of treatment followed by 1 week of rest. Clinical and neurological assessments were repeated at the end of every cycle and imaging was repeated every 3 months.

Reference

Chitnis T, Singhal T, Zurawski J, et al. Nasal anti-CD3 monoclonal antibody (Foralumab) reduces PET microglial activation and blood inflammatory biomarkers in two patients with nonactive secondary progressive MS. Poster presented at: Congress of the European Committee for Treatment and Research in Multiple Sclerosis 2022; October 26-28, 2022; Amsterdam, the Netherlands.