Investigational therapy evobrutinib, also known as M2951, can reduce relapse rates and brain lesions in people with relapsing forms of multiple sclerosis (MS), 48-week data from a Phase 2 clinical trial suggest.
Updated results from the trial (NCT02975349) were presented at the recent 2019 annual meeting of the American Academy of Neurology (AAN), in an oral presentation titled “Efficacy and Safety of the Bruton’s Tyrosine Kinase Inhibitor Evobrutinib in Patients with Relapsing Multiple Sclerosis over 48 Weeks: a Randomized, Placebo-Controlled, Phase 2 Study.”
In addition, some of the results were published in The New England Journal of Medicine, in an article titled “Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis.”
Evobrutinib, an oral experimental therapy being developed by Merck KGaA (known as EMD Serono in the U.S. and Canada), inhibits the protein Bruton’s tyrosine kinase (BTK). This protein is involved in the development and maturation of immune cells, particularly B-cells, which play a major role in driving inflammation in MS.
“Evobrutinib is the first Bruton’s tyrosine kinase inhibitor to demonstrate clinical proof of concept in multiple sclerosis,” Xavier Montalban, MD, PhD, a professor at the University of Toronto, said in a press release.
Montalban is also the director of the MS Centre at St. Michael’s Hospital in Canada, and chairman and director of the neurology-neuroimmunology department and neurorehabilitation unit, Multiple Sclerosis Centre of Catalonia, Vall d’Hebron University Hospital in Barcelona.
In the trial, 267 patients were randomly assigned to one of five groups: three groups received various doses of evobrutinib (25 mg once daily, 75 mg once daily, or 75 mg twice daily); a fourth was given a placebo; and the fifth group was given Biogen‘s Tecfidera (dimethyl fumarate).
It had previously been reported that, compared with placebo, the higher doses of evobrutinib — 75 mg once or twice daily — led to a significant reduction in the number of T1 gadolinium-enhancing lesions (lesions in the inflammatory phase) in the brains of MS patients after 24 weeks of treatment.
This new data now show that this reduction was maintained through 48 weeks of the treatment.
Additionally, the annualized relapse rate in patients given the highest dose of evobrutinib (75 mg twice daily) was 0.11, with 79% of patients having no relapses after 48 weeks. For comparison, the relapse rate among patients on the placebo group was 0.37 at 24 weeks.
In terms of safety, the most common side effects of evobrutinib treatment were nasopharyngitis — more commonly known as a cold — and increased levels of a liver enzyme called ALT, which can be indicative of liver damage. No infections or lymphopenia (reduced white blood cell count) were reported.
“Building on our initial analysis at 24 weeks, these new data further demonstrate the potential role of evobrutinib in relapsing multiple sclerosis, subject to further clinical investigation,” Montalban said. “We are pleased that these 48-week data further support our continued clinical development of evobrutinib and investigation into its efficacy for patients with MS.”