Fenebrutinib is a new drug treatment under investigation for relapsing remitting and primary progressive multiple sclerosis (MS). It is taken as a tablet once daily.
Fenebrutinib for relapsing remitting MS: Phase III
Fenebrutinib for primary progressive MS: Phase III
- Fenebrutinib interferes with the function of macrophages and microglia which have been linked to MS progression. It also affects 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, fenebrutinib reduced the number of new active lesions on MRI.
- In studies involving people with rheumatoid arthritis, the most common side effects included nausea, headache, anaemia, and chest infections.
Fenebrutinib 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.
Fenebrutinib 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 evobrutinib, tolebrutinib, orelabrutinib and remibrutinib.
Fenebrutinib is taken as a tablet, once daily.
Fenebrutinib has previously been studied in a number of autoimmune conditions including rheumatoid arthritis, systemic lupus erythematosus and chronic spontaneous urticaria.
FENopta – fenebrutinib compared to placebo
This phase II study recruited 103 participants with relapsing remitting MS who will took either fenebrutinib or placebo for up to 96 weeks. The FENopta trial found that the drug significantly reduced the number of MS lesions in the brains of people with relapsing MS using MRI scans. So far, no signs of liver toxicity have been seen, a side effect that caused problems for a small number of people taking other BTK inhibitors in trials.
Topline results published in a press release from the manufacturer reported that fenebrutinib significantly reduced MRI markers of disease activity. Further results will be presented at an up-coming scientific meeting.
Further details of FENopta
FENHANCE 1 and 2 – fenebrutinib compared to Aubagio (teriflunomide), in relapsing remitting MS
These identical phase III studies will recruit 1468 people with relapsing remitting MS or active secondary progressive MS. One half will take fenebrutinib and one half will take Aubagio (teriflunomide) for two years. The main measure is the number of relapses in a year. Other measures include worsening of disability which persists for three and six months, lesions visible on MRI scans, as well as changes in physical function and cognition.
Estimated completion date November 2025.
Further details of FENHANCE 1
Further details of FENHANCE 2
FENTREPID – fenebrutinib compared to Ocrevus (ocrelizumab) in primary progressive MS
This phase III study will recruit 946 participants with primary progressive MS who will take either fenebrutinib or Ocrevus for 120 weeks (about 2.3 years). The main aim of the study is to measure how fenebrutinib affects worsening disability using a combination of EDSS, walking and hand function. Side effects, changes in brain volume as measured on MRI scans, cognition and self-reported physical function will also be measured.
Estimated completion date December 2026.
Further details of FENTREPID
In a clinical trial which evaluated fenebrutinib in rheumatoid arthritis, the most common side effects included:
- nausea
- headache
- anaemia
- chest infections.
