Evobrutinib is a new drug being investigated for the treatment of relapsing MS. Phase 3 trials are recruiting following promising phase 2 results.

About evobrutinib

Evobrutinib is part of a new class of drugs called Bruton’s tyrosine kinase (BTK) inhibitors. BTK is a molecule that affects the activity of some immune cells.

Stopping BTK working properly reduces the activity of these immune cells. These cells have been linked to MS relapses. Researchers believe reducing their activity could reduce the damage caused to nerves.

As a tablet, twice daily.

Phase 2 trial

Merck, the company who designed evobrutinib, shared results of a phase 2 clinical trial in May 2019. The trial involved 267 people with relapsing MS. Participants took one of three doses of evobrutinib, a placebo (dummy drug) or dimethyl fumarate (Tecfidera).

The results showed that compared to the placebo, treatment with evobrutinib resulted in a significant reduction in new lesions and relapses.

Phase 3 trials

In October 2021, Merck announced recruitment for phase 3 clinical trials were complete. The two identical EVOLUTION trials have recruited 1860 people with relapsing MS. They will compare the efficacy of evobrutinib with an existing treatment called teriflunomide (Aubagio) over two years. The researchers want to know whether tolebrutinib is better at reducing relapses. They’ll also be looking at worsening of disability, lesions visible on MRI scans, physical function and fatigue.

In April 2023, the FDA (Food and Drug Administration, a US regulator) placed the EVOLUTION trials for evobrutinib on partial clinical hold. This was because two participants experienced liver injury. They had no symptoms and their livers returned to normal when they stopped taking the drug.

A partial clinical hold means people who have been taking the drug for 70 days or less have to stop. People who have been taking it for more than 70 days are allowed to complete the treatment.

Because they had finished recruitment, no-one had to leave the trial. The researchers expect to share results by the end of 2023.

A phase 1 clinical trial to test the safety profile of evobrutinib was completed in 2020. Results indicate it is well tolerated and poses no obvious safety concerns.

The primary side effects reported from the phase 2 clinical trial in 2019 were colds, and increases in blood levels in the liver. These increases in liver blood levels returned to normal when treatment was stopped and did not cause any symptoms.

Evobrutinib has not been widely tested in people with MS so it isn’t yet known how it compares to existing MS treatments. Phase 3 clinical trials are hoping to compare the efficacy of evobrutinib with that of teriflunomide (Aubagio).

Evobrutinib is currently being investigated in two phase 3 trials, with the results due in September 2023. If the results are positive, evonbrutinib will be submitted for regulatory approval.

Positive trial results can only make a real difference to people with MS once a regulator like the European Medicines Agency concludes there's sufficient evidence the drug is safe and effective.