Evobrutinib is a new drug treatment under investigation for relapsing remitting multiple sclerosis (MS). It is taken as a tablet once or twice daily.
Evobrutinib for relapsing remitting MS: Phase III
- Evobrutinib interferes with the function of macrophages which have been linked to MS progression and of B cells, a type of white blood cell which is involved in the immune response that damages the myelin coating of nerves
- In relapsing remitting MS, evobrutinib reduced the number of new active lesions on MRI and reduced the yearly relapse rate.
- In phase II studies, the most common side effects were common colds, and increased blood levels of liver enzymes.
Evobrutinib is also being developed as a treatment for rheumatoid arthritis and systemic lupus erythematosus.
Evobrutinib belongs to a group of medicines called Bruton's tyrosine kinase (BTK) inhibitors.
Bruton’s tyrosine kinase is an enzyme which is essential for the survival and activation of B-cells. B-cells are a type of white blood cell (lymphocyte) thought to be involved in the inflammation caused by MS which causes lesions in the brain and spinal cord and can lead to relapses. The enzyme also regulates immune cells in the brain called macrophages and microglia which have been linked to MS progression.
Evobrutinib blocks the actions of the enzyme and it is thought that this will prevent the MS activity which leads to relapses as well as the longer term damage to nerve cells which causes progression.
Other BTK inhibitors in the MS drug pipeline include tolebrutinib, fenebrutinib, remibrutinib and orelabrutinib.
Evobrutinib is taken as a tablet, twice daily.
In a phase II study, 267 people with relapsing MS took one of three doses of evobrutinib (25mg once daily, 75mg once daily or 75mg twice daily), placebo or Tecfidera. The main measure was the number of active lesions seen on MRI. After 24 weeks of treatment, people taking evobrutinib 75mg once daily had significantly fewer active lesions than those taking placebo. Compared to placebo, there was no significant difference for the other doses of evobrutinib (25mg once daily or 75mg twice daily). Over the 24 week study period there was no significant difference in relapse rate or disability progression for any dose compared to placebo.
Further results from this study were presented at a scientific meeting in 2022. After 48 weeks of treatment, evobrutinib decreased slowly expanding lesion (SEL) volume compared to placebo. SELs are thought to be associated with progression in MS, possibly driven by the activity of microglia and macrophages.
EVOLUTION RMS1 and RMS2 - evobrutinib compared to Aubagio (teriflunomide)
These identical phase III studies will recruit 1860 people with relapsing remitting MS. One half will take evobrutinib and the other Aubagio (teriflunomide) for approximately two years. The main measure for these studies is the number of relapses in a year. Additional measures include worsening of disability which persists for three and six months, lesions visible on MRI scans and participant reported scores for physical function and fatigue.
Estimated completion date September 2023.
Further details of EVOLUTION RMS1
Further details of EVOLUTION RMS2
In the phase II study, the most common side effects were colds, and increases in blood levels of liver enzymes which returned to normal levels when treatment was stopped and did not cause any symptoms.
Two cases of increased liver enzyme levels suggestive of evobrutinib-associated liver injury have been reported in clinical trials. Both participants had no symptoms, did not require any medical treatment and blood levels of liver enzymes returned to normal after treatment was stopped. In the States, recruitment to clinical trials has been suspended while further investigations are carried out.