Rilzabrutinib Tablets (Wayrilz)
October 15, 2025
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
The U.S. Food and Drug Administration (FDA) has approved rilzabrutinib, the first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, for the treatment of persistent or chronic immune thrombocytopenia. Rilzabrutinib is distributed by Genzyme Corporation as Wayrilz.
Indications
Rilzabrutinib is indicated for the treatment of adult patients with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to previous treatment.1
Dosage
The recommended dose is one tablet (400 mg) twice daily taken with water and without regard to food.1 It should be taken at least two hours before administration of an antacid or H2 receptor antagonist. Concomitant use of a proton pump inhibitor should be avoided. Rilzabrutinib is available as 400-mg tablets.
Potential Advantages
Rilzabrutinib has demonstrated clinical benefit in patients with persistent/chronic ITP who failed multiple prior therapies.2
Potential Disadvantages
Rilzabrutinib increases the risk of serious infections (e.g., bacterial, viral, or fungal); hepatotoxicity, including severe, life-threatening, and potentially fatal cases; and embryo-fetal toxicity.1 Common (> 10% vs. placebo) adverse reactions include diarrhea (32% vs. 10%, respectively), nausea (20% vs. 6%, respectively), headache (18% vs. 7%, respectively), abdominal pain (14% vs. 1%, respectively), COVID-19 (14% vs. 4%, respectively), and neutropenia (11%). Rilzabrutinib is a substrate of CYP3A4. Concomitant administration with moderate or strong CYP3A inhibitors and inducers should be avoided. Rilzabrutinib also is an inhibitor and inducer of CYP3A as well as an inhibitor of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion-transporting polypepties 1B (OATPIB) and may affect the exposure of drugs that are substrates for this enzyme or these transporters.
Comments
Rilzabrutinib is a covalent, reversible BTK inhibitor that acts through multiple immune modulation mechanisms, including inhibition of B cell activation and decreasing autoantibody production, thus preventing cell phagocytosis by Fc gamma receptors in the spleen and liver.1,2 Its efficacy was evaluated in a randomized, double-blind, placebo-controlled trial in study participants with primary persistent or chronic ITP (LUNA-3). Participants had a median age of 47 years, 63% were female, 62% were Caucasian, there was a median of 7.7 years since ITP diagnosis, 28% had prior splenectomy, and the median platelet count was 15.3 × 109/L. Participants had unsustained responses to either intravenous immunoglobulin (IVIg/anti-D) or corticosteroids, or they had a documented intolerance or insufficient response to any appropriate course of standard-of-care therapy. Participants were randomized to the rilzabrutinib (n = 133) or placebo (n = 69) arms for 24 weeks. The primary endpoint was durable platelet response: weekly platelet count of ≥ 50 x 109/L for two-thirds or more of at least eight non-missing weekly scheduled platelet measurements during the last 12 weeks of the 24-week double-blind period in the absence of rescue therapy. At least two non-missing weekly counts of ≥ 50 x 109/L had to be during the last six weeks of the 24-week blinded treatment period. Secondary endpoints included the number of weeks with a platelet response of ≥ 50 x 109/L or between 30 × 109/L and 50 × 109/L, and double from baseline, time to platelet response, percent of participants requiring rescue therapy and change from baseline at week 13 on a 10-item of the Immune Thrombocytopenic Purpura-Patient Assessment Questionnaire (ITP-PAQ) (for physical fatigue). Durable platelet response rate was 23% for rilzabrutinib vs. 0% for placebo, mean number of weeks with platelet response was 7.18 (0.75) vs. 0.72 (0.35), and median days to first platelet response was 36 days vs. not reaching response for placebo. Percent requirement for rescue medication was 33% vs. 58%, respectively. Improved ITP-PAQ scores were observed with rilzabrutinib as early as week 5 and sustained from week 13 through 25.3
Clinical Implications
ITP is an acquired autoimmune disorder characterized by reduced platelet counts and increased risk of bleeding. It is caused by dysfunction of the immune system at multiple levels, including platelet destruction mediated by autoantibodies targeting glycoproteins (GPIIb and GPIb/IX), leading to Fc gamma receptor-dependent phagocytosis, complement-mediated clearance in the spleen and liver, as well as megakaryocyte dysfunction.4 Prevalence is estimated to be 10 and 23 per 100,000 individuals and a higher prevalence in females younger than 70 years of age.5 First-line therapy is corticosteroids and intravenous immunoglobulin.5 Second-line therapies include thrombopoietin-receptor agonist (romiplostim, eltombopag, avatrombopag), or splenectomy. Several BTK inhibitors are in clinical development, with rilzabrutinib being the first to gain FDA approval. Rilzabrutinib provides an effective option for patient who do not respond adequately or are intolerant to first- or second-line therapies. Rilzabrutinib costs $17,500 for a 30-day supply.
William T. Elliott, MD, FACP, is Assistant Clinical Professor of Medicine, University of California, San Francisco.
James Chan, PharmD, PhD, is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
References
- U.S. Food and Drug Administration. Wayrilz prescribing information. Genzyme Corporation. Revised August 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219685s000lbl.pdf
- Kuter DJ, Ghanima W. Evaluating rilzabrutinib in the treatment of immune thrombocytopenia. Immunotherapy. 2025;17(11):767-782.
- Kuter DJ, Ghanima W, Cooper N, et al. Safety and efficacy of rilzabrutinib vs. placebo in adults with immune thrombocytopenia: The Phase 3 LUNA3 study. Blood. 2025;145(24):2914-2926.
- Martínez-Carbelleira D, Bernardo Á, Caro A, et al. Pathophysiology, clinical manifestations and diagnosis of immune thrombocytopenia: Contextualization from a historical perspective. Hematol Rep. 2024;16(2):204-219.
- Labanca C, Martino EA, Vigna E, et al. Rilzabrutinib for the treatment of immune thrombocytopenia. Eur J Haematol. 2025;115(1):4-15.
The U.S. Food and Drug Administration has approved rilzabrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor, for the treatment of persistent or chronic immune thrombocytopenia. Rilzabrutinib is distributed by Genzyme Corporation as Wayrilz.
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