Fenebrutinib is an investigational oral medication currently undergoing clinical development. It is being studied for its potential use in treating a range of autoimmune diseases. This compound is part of a newer class of targeted therapies, designed to interfere with specific pathways involved in immune responses.
How Fenebrutinib Works
Fenebrutinib functions as a Bruton’s tyrosine kinase (BTK) inhibitor. BTK is an enzyme found within cells that plays a significant role in the signaling pathways of various immune cells, particularly B-cells and myeloid lineage cells like macrophages and microglia. In healthy individuals, BTK helps regulate the development and activation of B-cells, a type of white blood cell involved in the body’s immune response.
When BTK is inhibited by fenebrutinib, it blocks the enzyme’s activity, interfering with signaling pathways that drive inflammation and unwanted immune responses. This interruption reduces the activation, proliferation, and survival of B-cells, which are often overactive in autoimmune conditions. Fenebrutinib is a reversible and non-covalent inhibitor, meaning it temporarily binds to and blocks BTK’s function. It is highly selective for BTK.
Conditions Fenebrutinib Targets
Fenebrutinib is under investigation for its potential to treat several autoimmune diseases where immune system overactivity contributes to the condition. A primary focus of its development is multiple sclerosis (MS), a chronic disease affecting the brain, spinal cord, and optic nerves. In MS, the immune system mistakenly attacks the protective myelin sheath around nerve cells, leading to inflammation and damage.
Fenebrutinib’s ability to inhibit both B-cell and microglia activation is thought to be beneficial in MS, potentially reducing disease activity and slowing disability progression. Clinical trials in relapsing forms of MS have shown fenebrutinib can significantly reduce brain lesions, which are markers of MS disease activity, compared to a placebo. It is also being evaluated for primary progressive MS. Beyond MS, fenebrutinib has been studied in other autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus (SLE), and chronic spontaneous urticaria (CSU).
Current Research and Safety Considerations
Fenebrutinib is an investigational drug undergoing rigorous testing in clinical trials and has not yet received approval from regulatory bodies like the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). Its development program includes Phase I, II, and III clinical trials, involving over 2,500 individuals across various diseases.
While fenebrutinib has shown a generally consistent safety profile, some side effects have been observed. The most common adverse events reported in Phase II trials for MS included elevated liver enzymes (hepatic transaminases), urinary tract infections, COVID-19, and pharyngitis (sore throat). In November 2023, the U.S. FDA placed a partial clinical hold on the fenebrutinib MS development program in the U.S. due to two cases of elevated liver enzymes combined with elevated bilirubin, suggesting drug-induced liver injury. Both patients were asymptomatic, and their liver enzyme levels returned to normal after discontinuing the drug. While new enrollment in the U.S. for some Phase III MS trials was paused, enrollment continues in other countries.