Remibrutinib Tablets (Rhapsido)

By William Elliott, MD, FACP, and James Chan, PharmD, PhD

The U.S. Food and Drug Administration has approved a second Bruton’s tyrosine kinase inhibitor (BTKi), remibrutinib, for the treatment of chronic spontaneous urticaria (CSU) in adults who remain symptomatic despite antihistamine treatment. The first BTKi, rilzabrutinib (Wayrilz), was approved for chronic immune thrombocytopenia. Remibrutinib is distributed by Novartis Pharmaceuticals Corporation as Rhapsido.

Indications

Remibrutinib is indicated for the treatment of CSU in adult patients who remain symptomatic despite H1 antihistamine treatment.¹

Dosage

The recommended dose is 25 mg twice daily with or without food.¹ The dosing regimen should be interrupted for three to seven days pre- and post-surgery.

Potential Advantages

Remibrutinib, as a selective BTK inhibitor, offers an orally effective treatment for CSU in patients who remain symptomatic despite being treated with second-generation H1-antihistamines.²

Potential Disadvantages

In placebo-controlled studies, mucocutaneous-related bleeding occurred in 9% of participants treated with remibrutinib, compared to 2% in those treated with placebo.¹ Mild or moderate transient petechiae were reported in the remibrutinib-treated group (3.8%) vs. 0.3% in the placebo-treated group.²Remibrutinib should be interrupted for three to seven days pre- and post-surgery or invasive procedures.¹ Remibrutinib is a substrate of cytochrome P450 3A4 (CYP3A4 ). Therefore, the use of strong or moderate CYP3A4 inhibitors and inducers should be avoided.¹ Remibrutinib is a P-glycoprotein (P-gp) inhibitor. Monitoring for adverse reactions is advised when remibrutinib is administered concomitantly with P-gp substrates.

Comments

Remibrutinib blocks BTK-mediated degranulation of mast cells and basophils, preventing the release of histamine and other proinflammatory compounds mediated by pathogenic immunoglobulin E (IgE) or immunoglobulin G.¹ Its efficacy was evaluated in two identical 52-week, randomized, double-blind, placebo-controlled trials (REMIX-1, REMIX-2) in participants who remained symptomatic despite H1-antihistamine treatment — defined by the presence of itch and hives for ≥ 6 consecutive weeks.^1,2 All participants were required to have a weekly urticaria activity score (UAS7) of ≥ 16, a weekly itch severity score (ISS7) of ≥ 6, and a weekly hives severity score (HSS7) of ≥ 6 for seven days prior to randomization. The mean age of participants was 44 years; 67% were female; 55% were white; and 63% had UAS7 scores of ≥ 28, a mean HSS7 score of 16, and a mean ISS7 score of 15; and about 30% had previous exposure to anti-IgE biologics (e.g., omalizumab). Participants were randomized to remibrutinib (n = 309 [REMIX-1], n = 297 [REMIX-2]) or placebo (n = 153 [REMIX-1], n = 153 [REMIX-2]) along with background H1-antihistamine. The co-primary endpoints were absolute change from baseline in ISS7 and HSS7 at week 12. ISS7 was defined as the sum of the daily itch severity scores (range 0 to 3) recorded over a seven-day period (range 0 to 21) and HSS7 sum of daily hive severity scores over a seven-day period (0 to 21). Secondary endpoints included the proportion of participants who achieved UAS7 ≤ 6 at weeks 2 and 12, and the proportion of participants who achieved complete absence of itch and hives (UAS7 = 0) at week 12. Remibrutinib produced significant reductions in ISS7 and HSS7 in both studies (mean differences vs. placebo of -2.63 and -3.23 in ISS7 and -3.61 and -4.47 in HSS7). These represented an 18% to 23% reduction from baseline ISS7 and reductions of 23% to 28% from baseline HSS7. Proportion of participants achieving UAS7 ≤ 6 (vs. placebo) at week 2 were 33.7% vs. 3.3% and 30% vs. 5.9%, respectively. At week 12, proportions were 49.8% vs. 24.8% and 46.8% vs. 19.6%. Proportion of participant achieving UAS7 = 0 (vs. placebo) were 31.1% vs. 10.5% and 27.9% vs. 6.5% in the two studies, respectively. Decrease in symptoms appeared to occur as early as week 1.² Efficacy was maintained up to 52 weeks with a consistent favorable safety profile in a Phase IIb study.³

Clinical Implications

CSU is an inflammatory skin disease affecting approximately 1% of the general population.⁴ It is characterized by unpredictable itching, hives, and/or angioedema for more than six weeks. It is more common in females aged 30 to 50 years. Second generation H1-antihistamines are the first-line treatment, with omalizumab considered a second-line treatment.⁴ Remibrutinib now provides an orally active option. There currently are no published studies comparing omalizumab and remibrutinib. In placebo-controlled trials, improvements in ISS7 and HSS7 at week 12 for remibrutinib were similar in magnitude to those reported for omalizumab 75 mg and 150 mg administered every four weeks, but numerically less than reported for omalizumab 300 mg.^1,5 In a network meta-analysis comparing omalizumab, dupilumab, and remibrutinib, omalizumab
300 mg every four weeks consistently showed the greatest efficacy across major outcomes, followed by remibrutinib.⁶ A comparative trial between omalizumab 300 mg every four weeks vs. remibrutinib (25 mg twice daily) is in progress (NCT06042478) (n = 470), with an estimated completion date of July 2027. The cost for remibrutinib is $4,521 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

1. Novartis Pharmaceuticals Corporation. Rhapsido prescribing information. Revised September 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218436s000lbl.pdf

2. Metz M, Giménez-Arnau A, Hide M, et al. Remibrutinib in chronic spontaneous urticaria. N Engl J Med. 2025;392(10):984-994.

3. Jain V, Giménez-Arnau A, Hayama K, et al. Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks. J Allergy Clin Immunol. 2024;153(2):479-486.

4. Kolkhir P, Bonnekoh H, Metz M, Maurer M. Chronic spontaneous urticaria: A review. JAMA. 2024;332(17):1464-1477.

5. Genetech, Inc. Xolair prescribing information. Revised February 2024.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/103976s5245lbl.pdf

6. Xiong G, Rayner DG, Kim S, et al. Comparative efficacy of omalizumab, dupilumab, and remibrutinib in chronic spontaneous urticaria: A network meta-analysis of randomized control trials. J Dermatolog Treat. 2025;36(1):2580374.