Experimental Medications: Administered Orally
Company: EMD Serono
- Oral medication being studied at 75 mg once and twice daily
- Being studied in RMS
Two simultaneous Phase III clinical trials – EVOLUTION RMS 1 and EVOLUTION RMS 2 – will be testing the efficacy of the oral investigational medication evobrutinib for delaying neurologic and functional decline in people with relapsing forms of MS (RMS).
In a previous Phase II trial, evobrutinib reduced the total cumulative number of T1 gadolinium-enhancing (Gd+) lesions compared with placebo. The reduction in Gd+ T1 lesions was seen at 12 weeks and maintained through 48 weeks with evobrutinib 75 mg once or twice daily. Reductions in relapse rates were also observed at week 24 and were maintained through 48 weeks.16
Evobrutinib is a highly selective inhibitor of Bruton’s tyrosine kinase (BTK), a non-receptor enzyme. BTK contributes to the development and function of B lymphocytes, a type of white blood cell that can attack and destroy the neuroprotective myelin sheath that surrounds nerve cells in the brain and spinal cord. Evobrutinib is formulated to inhibit the primary B cell actions that lead to abnormal immune responses and, ultimately, neurodegeneration. It is hoped that through this mechanism of action, neurologic and functional decline will be delayed or even prevented.16
In another Phase II clinical trial, evobrutinib at different dosages did not appreciably reduce total B cells or immunoglobulin levels. This finding suggests that BTK inhibition, which is often employed to treat certain cancers, may not kill enough myelin-damaging cells and proteins to effectively combat MS.37 Still, however, the preliminary findings that point to evobrutinib’s effect on lesions and relapses give investigators reason to hope.
EVOLUTION RMS 1 and 2 are two-year, randomized, double-blind studies comparing twice-daily evobrutinib with interferon beta-1a (given intramuscularly once weekly). Researchers in both studies will record changes in annualized relapse rates, time to first occurrence of 12- and 24-week confirmed disability progression, and total number of lesions based on magnetic resonance imaging readings.16 Study completion for evaluation of primary results is expected sometime in 2023.68