Orelabrutinib is an existing anti-cancer drug being investigated for the treatment of relapsing MS. A phase 2 trial is currently recruiting.

About orelabrutinib

Orelabrutinib 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 those immune cells.

These cells have been linked to MS relapses. Researchers believe reducing their activity could reduce damage caused to nerves.

As a tablet, however dosage is not set.

Phase 2 trial

A phase 2 clinical trial aims to recruit 160 people with relapsing MS. Participants will take either orelabrutinib or a placebo (dummy drug) for the initial 12 weeks. The researchers want to know whether orelabrutinib is effective for preventing the formation of lesions visible on MRI scans. Over a longer term, the researchers will also be looking at the effect of orelabrutinib on annualised relapse rates. 

In December 2022, the FDA (Food and Drug Administration, a US regulator) placed this trial for orelabrutinib on partial clinical hold. This was because a small number of participants experienced liver injury. Their livers returned to normal when they stopped taking the drug.

New participants can't be enrolled into the trial. And, people who had been taking the drug for 70 days or less had to stop. People who had been taking it for more than 70 days were allowed to complete the treatment.

Because the trial had almost finished recruitment, the researchers will collect the data from everyone who already joined. They expect to have results in 2024.

Orelabrutinib is a licensed anti-cancer treatment in the US and China, approved by the NMPA and FDA in 2020 and 2021 respectively. 

Orelabrutinib has not yet been widely tested in people with MS, so its side effects specifically for people with MS are not yet known.

The phase 3 trial by Merck showed two participants experienced liver injury. Both patients showed no symptoms, and did not require hospitalization. But, their livers were releasing abnormal enzymes. Their livers returned to normal when they stopped taking the drug.

Orelabrutinib has not been widely tested in people with MS so it isn’t yet known how it compares to existing MS treatments.

Orelabrutinib is currently being investigated in a phase 2 trial, with the results due in March 2024. If the results are positive, recruitment for phase 3 trials will begin. If the phase 3 results are also positive, orelabrutinib 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.