Overview of BTK Inhibitors in Development for CSU Treatment

Author(s):

Giselle Mosnaim, MD, MS ,Shyam Joshi, MD

Panelists discuss how newer Bruton tyrosine kinase (BTK) inhibitors being developed for chronic spontaneous urticaria (CSU), particularly remibrutinib (in phase 3 trials) and rilzabrutinib (in phase 2), are designed to be more selective than earlier oncology-focused BTK inhibitors, potentially reducing off-target effects like bleeding, cardiovascular complications, and GI issues.

EP: 1.Chronic Spontaneous Urticaria and Bruton Tyrosine Kinase: A Multispecialty Expert Discussion

EP: 2.Pathophysiology of Chronic Spontaneous Urticaria

EP: 3.Current CSU Treatment Approach and the Role of Bruton Tyrosine Kinase

EP: 4.BTK Inhibition as a Strategy for CSU Treatment

EP: 5.How BTK Inhibitors Differ From Current CSU Treatment Approaches

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EP: 6.Overview of BTK Inhibitors in Development for CSU Treatment

EP: 7.Differentiating BTK Inhibition From Genetic BTK Deficiency

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Let’s talk a bit about the BTK inhibitors currently being developed and studied for the treatment of CSU:
Remibrutinib: phase 3 trials, with 12-, 24-, and 52-week data available; inhibits BTK in mast cells, basophils, and B cells
Rilzabrutinib: currently in phase 2 trials
How do the BTK inhibitors under development for CSU treatment differ from earlier generations of BTK inhibitors used in oncology and other autoimmune diseases?
Older BTK inhibitors have limited selectivity and irreversibly inhibit additional kinases, increasing potential for off-target adverse effects (AEs; bleeding effects, cardiotoxicity [hypertension, atrial fibrillation], gastrointestinal effects, and rash).
Remibrutinib binds to the inactive conformation of BTK and shows higher selectivity, limiting the potential for these off-target AEs