Long-Term Efficacy and Safety of Evobrutinib for Multiple Sclerosis Results Over 144-Week Clinical Studies

In the open-label extension of a phase 2 clinical trial (NCT02975349), participants with multiple sclerosis (MS) treated with the investigational Bruton tyrosine kinase inhibitor evobrutinib (EMD Serono, Rockland, MA) continued to have a low annualized relapse rate (ARR). For individuals treated with 75 mg evobrutinib twice daily in the double-blind period of the study, the ARR was 0.12 (95% CI: 0.07-0.20) over 132 weeks of treatment, similar to what is seen with available, highly efficacious MS treatments. Across all groups of participants, the mean ARR value was reduced upon switching to a dose of 75 mg evobrutinib twice daily.

Participants also had no increase in disability as Expanded Disability Status Scale (EDSS) scores remained stable with a mean of mean of 3.28 at week 144 vs 3.27 at baseline.

There were no increases in abnormal liver function test results, either with increased doses or prolonged use of evobrutinib. The majority of participants had normal IgG levels at week 132, and in those with low CD19+ B-cell counts (<107 cells/mcL), no associated infections were observed. Frequency of severe (Grade ≥3) infections was low at 4.2%, although 3 of these individuals had fatal infections (2 COVID-19 pneumonia, 1 E. coli sepsis) that were considered not to be treatment related.

The most common treatment-emergent adverse events were nasopharyngitis (11.3%), increased lipase levels (11.3%), headache (8.0%), upper respiratory tract infections (5.6%) and urinary tract infections (6.1%). 

Davorka L. Tomic, DVM, PhD, VP and Head of Global Clinical Development, Neurology at Merck KGaA, Darmstadt, Germany said, "These long-term data from the patients who participated in the evobrutinib phase 2 MS study indicate that evobrutinib, if approved as a treatment for MS, has a potential to become a promising and convenient-to-take oral treatment option with a positive benefit-risk profile, which we expect to be further confirmed by the data of the ongoing phase 3 trials.” 

These data were presented at the American Academy of Neurology meeting April 2022 and at the Consortium of Multiple Sclerosis Centers in June 2022.