B-cells produce antibodies, present antigens, stimulate and activate T-cells, and produce proinflammatory cytokines, among other functions.
The interest in B-cells in the disease progression of MS has been piqued by the anti-inflammatory effect of antibodies that target the B-cell surface marker CD20 … and the effect of such antibodies in primary progressive MS.
Bruton’s tyrosine kinase (BTK) is involved in the regulation of B cells and myeloid cells that are believed to be involved in the pathogenesis of multiple sclerosis. If BTK could be inhibited, then this might affect the progression of the disease. Such a drug, evobrutinib, is being developed by Merck KGaA to treat multiple sclerosis.1
In a double blind, randomised Phase II trial, 267 patients aged 65 and older with relapsing multiple sclerosis were given 25 or 75 mg of evobrutinib once a day, 75 mg twice a day, open label 240 mg doses of dimethyl fumarate (DMF) or a placebo.2
The primary endpoint was the total number of gadolinium-enhancing lesions at weeks 12, 16, 20 and 24. Placebo-treated patients were switched to 25 mg of evobrutinib after 24 weeks.
The baseline adjusted rate ratios for the total number of lesions compared with the placebo were 1.45 with the lowest dose, 0.3 with 75 mg/day and 0.44 in the twice daily dosed group.
The unadjusted annualised relapse rate at week 24 was 0.37 with the placebo, and 0.57, 0.13 and 0.08, respectively, for the three dose groups; it was 0.20 with DMF. It was well tolerated at all doses. Further trials are planned.
References
- P. Haselmayer, et al., J. Immunol. 202, 2888 (2019).
- X. Montalban, et al., N. Engl. J. Med. (2019): epub ahead of print, doi: 10.1056/NEJMoa1901981.