Merck’s MS Therapy Evobrutinib Significantly Reduces Brain Lesions, Phase 2 Trial Shows

Merck KGaA’s evobrutinib led to significant reductions in relapsing multiple sclerosis patients’ brain and spinal cord lesions, compared with a placebo, a Phase 2b clinical trial showed.

Researchers measured the number of lesions at weeks 12, 16, 20 and 24.

Evobrutinib, also known as M2951, is an oral inhibitor of a protein called Bruton’s tyrosine kinase (BTK), which is vital for the development and functioning of several immune cells. These include antibody-producing B-cells and macrophages.

By inhibiting BTK, evobrutinib suppresses autoantibody-producing cells. Preclinical-trial studies have suggested it could be an effective treatment for autoimmune diseases such as MS.

The ongoing Phase 2b trial (NCT02975349) is taking place at the EMD Serono Research & Development Institute in the United States. It enrolled 267 patients with relapsing MS.

Participants were randomized to receive either evobrutinib, a placebo, or Tecfidera (dimethyl fumarate), a disease-modifying drug approved for relapsing-remitting MS.

Those in the evobrutinib group are receiving one of three doses — low, medium or high — for 48 weeks (11 months).

Patients in the placebo group are receiving a placebo for 24 weeks, followed by low-dose evobrutinib for another 24 weeks.

The therapy comparison group is receiving a 120-mg hard capsule of Tecfidera twice a day for seven days, then a 240-mg hard capsule twice a day for 47 weeks.

Researchers said the trial’s primary endpoint is seeing how many gadolinium-enhancing T1 lesions there are in the three groups at different stages of the treatment. Another endpoint is an assessment of patients’ annualized relapse rate (ARR).

According to the trial page, researchers define a relapse as “new, worsening or recurrent neurological symptoms attributed to multiple sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.”

In addition, a relapse has to be accompanied by new signs of worsening during a neurological examination or an increase in patients’ Expanded Disability Status scale score.

“We are encouraged by these early positive results of evobrutinib in relapsing MS,” Luciano Rossetti, head of Global Research & Development at the Biopharma business of Merck KGaA in Darmstadt, Germany, said in a press release.

“The trial will continue so as to further inform our clinical development strategy for evobrutinib in MS,” Rossetti added.

Evobrutinib is also being evaluated as a therapy for rheumatoid arthritis and systemic lupus erythematosus.