Positive Phase 2 Results for Evobrutinib Treatment of MS and Initiation of Phase 3 Trials 

At the European Committee on Research and Treatment in Multiple Sclerosis (ECTRIMS) Congress in Stockholm, Sweden September 11-13, 2019, data from a phase 2 trial (NCT02975349) of evobrutinib (EMD Serono, Rockland, MD) for treatment of relapsing multiple sclerosis (MS) will be presented. Evobrutinib inhibits Bruton’s tyrosine kinase, the deletion of which depletes B cells and reduces circulating immunoglobulin (Ig). During the phase 2 trial, however, inhibition of Bruton’s tyrosine kinase with evobrutinib treatment did not have significant effects on B cells or Ig levels. 

Initiation of 2 phase 3 clinical trials (EVOLUTION RMS 1 and 2; NCT04032158 and NCT04032171) has been announced, and the announcement included more data from the phase 2 trial. 

Participants in the phase 2 trial who were treated with evobrutinib vs placebo had significant reductions in cumulative T1 gadolinium-enhancing (Gd+) lesions over 24 weeks of treatment. The T1 Gd+ lesion reduction was observed at the first MRI study, done at 12 weeks of treatment and was also maintained through 48 weeks when another MRI was done. Reduction of lesions and ARR was seen in both participants give 75 mg/day or 150 mg/day of evobrutinib compared with those given placebo. Relapse reduction observed at week 24 was maintained through 48 weeks. 

"Evobrutinib is a potential innovation for people living with MS, as it may offer a novel dual mechanism of action that is thought to impact myeloid cells in addition to B-cells and thus could address MS pathobiology in a fundamentally new way," said Luciano Rossetti, head of Global R&D for EMD Serono. "Evobrutinib, which was developed in our own laboratories, is an oral, highly selective BTK inhibitor that has shown clinical proof of concept in RMS. Progressing this molecule into phase 3 is an important step for us and the MS community, with an opportunity to further advance on benefit-risk considerations for RMS patients."

Nasopharyngitis and reversible increases in alanine aminotransferase (ALT) or aspartate aminotransferase (AST), or lipase were the most commonly observed adverse events in participants treated with evobrutinib. Over 52 weeks of treatment, 85% of participants (n = 267) completed the study. 

In the EVOLUTION RMS 1 and 2 trials, participants will be randomly assigned to receive evobrutinib (75 mg twice/day) or intramuscular interferon beta-1a weekly on a double-blind basis. The primary study measure will be annualized relapse rate (ARR) after 96 weeks of treatment. Secondary endpoints include time disability progression, total number of Gd+ T1 lesions, and new or enlarging T2 lesions.
In collaboration with the Accelerated Cure Project (ACP) for Multiple Sclerosis and its iConquerMS people-powered research network patient-reported outcomes (PRO) were also chosen, including change from baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Physical Function (PF) and the PROMIS MS Fatigue Scores at 96 Weeks. 

Trial recruitment is currently underway with the goal of 1,900 patients enrolled. The target completion is in June 2023.