Other names: GDC-0853


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

Phase 3

Fenebrutinib for primary progressive MS: Phase III

Phase 3

  • Fenebrutinib interferes with the function of macrophages and microglia 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, 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.

How does fenebrutinib work?

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 evobrutinibtolebrutinib, orelabrutinib and remibrutinib.

How is fenebrutinib taken?

Fenebrutinib is taken as a tablet, once daily.

Fenebrutinib research

What are the results so far?

Initial studies have investigated the effectiveness of fenebrutinib in a number of autoimmune conditions including rheumatoid arthritis, systemic lupus erythematosus and chronic spontaneous urticaria.

What further research is planned?

FENopta – fenebrutinib compared to placebo

This phase II study aims to recruit 102 participants with relapsing remitting MS who will take either fenebrutinib or placebo for up to 96 weeks. The study will evaluate the effect of fenebrutinib on brain MRI.
Estimated completion date March 2023.

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

Side effects

In a clinical trial which evaluated fenebrutinib in rheumatoid arthritis, the most common side effects included:

  • nausea
  • headache
  • anaemia
  • chest infections.
Weber M, et al.
Fenebrutinib demonstrates the highest potency of Bruton Tyrosine Kinase Inhibitors (BTKis) in phase 3 clinical development for multiple sclerosis (MS) (4437)
Neurology Apr 2021, 96 (15 Supplement) 4437
Summary (link is external)
Herman AE, et al.
Safety, pharmacokinetics, and pharmacodynamics in healthy volunteers treated with GDC-0853, a selective reversible Bruton's Tyrosine Kinase Inhibitor.
Clin Pharmacol Ther. 2018 Jun;103(6):1020-1028.
Summary (link is external)
On this page