Rilzabrutinib

Bruton's tyrosine kinase; BTK; Bruton's tyrosine kinase inhibitor;  

Rilzabrutinib is an orally administered, reversibly covalently binding inhibitor of Bruton’s tyrosine kinase (BTK). The active ingredient belongs to the group of newer-generation BTK inhibitors and possesses both immunomodulatory and anti-inflammatory properties.

 Rilzabrutinib binds reversibly and covalently to the cysteine residue Cys481 of BTK and inhibits its enzymatic activity. This affects several immunological signaling pathways:

• B lymphocytes: Inhibition of B-cell receptor signal transduction and, consequently, B-cell activation.
• Mast cells and basophils: Inhibition of FcεRI-mediated activation and degranulation.
• Macrophages and monocytes: Attenuation of Fcγ receptor-mediated inflammatory responses.

Special feature: Unlike irreversible BTK inhibitors such as remibrutiniband others, the covalent binding of rilzabrutinib is reversible. BTK inhibition can thus persist beyond the immediate exposure phase despite a relatively short plasma half-life.

BTK (see below: BTK gene) is an intracellular signaling molecule. BTK is found in B cells. There, its signaling regulates survival, proliferation, and maturation. BTK is involved in several inflammatory pathways that lead to the activation of the NLRP3 inflammasome as well as to signaling via the Fc-gamma receptor (FcγR) and Toll-like receptors.

Treatment of immune thrombocytopenia (ITP) in adults who are refractory to other therapies (EU approval since December 2025). Dosage: 400 mg orally twice daily. If the platelet count does not rise sufficiently, discontinue treatment after 12 weeks at the latest, in accordance with the prescribing information. In the Phase III LUNA-3 study, 23.3% of treated patients achieved a sustained platelet response, compared with 0% in the placebo group.

In clinical trials:

• Chronic spontaneous urticaria(CSU/experimental): Rilzabrutinib inhibits IgE-mediated degranulation in mast cells and basophils. In a larger randomized study, 160 omalizumab-naive patients and patients with an incomplete response to omalizumab were treated with rilzabrutinib. The primary analysis population consisted exclusively of the 143 omalizumab-naive patients. At week 12, significant reductions in the ISS7 score from baseline were observed with rilzabrutinib 1200 mg/day compared with placebo. CSU-related biomarkers, including soluble Mas-related G protein-coupled receptor X2, soluble Mas-related G protein-coupled receptor X2, immunoglobulin (Ig)G anti-thyroid peroxidase, IgG anti-Fcε receptor 1, and interleukin-31, were reduced at Week 12 compared with placebo. Rilzabrutinib demonstrated a favorable risk-benefit profile (Giménez-Arnau A et al. 2025):
• Pemphigus vulgaris 

Recommended dose (oral): 400 mg twice daily.   

Diarrhea, nausea, headache, abdominal pain, nasopharyngitis, and joint pain.

Clinically relevant interactions occur, in particular, with drugs that modulate CYP3A.

Rilzabrutinib has been available on the German market under the brand name^Wayrilz® since October 1, 2026. Approved indication: Treatment of immune thrombocytopenia (ITP) in adult patients who are refractory (resistant) to other therapies.

1. EMA: Wayrilz – Approval and Clinical Efficacy
2. EMA: German Prescribing Information for Rilzabrutinib
3. G-BA: Benefit Assessment Procedure 2026
4. Giménez-Arnau A et al. (2025) Rilzabrutinib in Antihistamine-Refractory Chronic Spontaneous Urticaria: The RILECSU Phase 2 Randomized Clinical Trial. JAMA Dermatol 161:679-687.
5. Maurer M et al. (2024) Dupilumab in patients with chronic spontaneous urticaria (LIBERTY-CSU CUPID): Two randomized, double-blind, placebo-controlled, Phase 3 trials. J Allergy Clin Immunol 154:184–194.