FDA Approves Remibrutinib for Chronic Spontaneous Urticaria

The US Food and Drug Administration (FDA) approved remibrutinib (Rhapsido), a highly selective Bruton’s tyrosine kinase (BTK) inhibitor, for adults with chronic spontaneous urticaria (CSU).1

Novartis announced the approval on September 30, 2025. Remibrutinib represents a new oral option for patients with CSU whose symptoms remain uncontrolled despite antihistamine therapy and provides an alternative to omalizumab, the current standard biologic treatment. Approximately 40 million people worldwide have CSU, characterized by hives lasting ≥ 6 weeks, and more than 50% of individuals with this condition do not respond to H1-antihistamines alone.2

“CSU is a serious disease that can cause debilitating symptoms and unpredictable flares. It’s difficult to diagnose and manage,” said Mark Lebwohl, MD, dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai and member of the steering committee for the remibrutinib REMIX Phase III clinical trial program, in a statement. “Remibrutinib represents a new way of treating CSU. By blocking the activity of BTK, remibrutinib stops a key pathway of the immune response in CSU. This is an exciting new option that has the potential to help a broad range of patients get fast relief.”

The approval is supported by results from the phase 3 REMIX-1 and REMIX-2 trials. Both studies demonstrated that remibrutinib produced early and substantial reductions in CSU symptoms, with improvements sustained for up to 52 weeks.2,3 The therapy acts by inhibiting the BTK pathway, which prevents histamine release and, in turn, reduces hives and angioedema. When used in combination with standard-dose antihistamines, remibrutinib addresses both histamine release and histamine receptor activity.

REMIX-1 (n = 470) and REMIX-2 (n = 455) were multicenter, double-blind, global, randomized, placebo-controlled phase 3 studies that evaluated twice-daily remibrutinib (25 mg) among adults with CSU who did not respond well to second-generation H1-antihistamines.2,3 All participants, no matter whether they were in the active or placebo arm, received a second-generation H1-antihistamine.

The primary outcomes included the change from baseline in weekly urticaria activity score (UAS7), weekly itch severity score (ISS7), and weekly high severity score (HSS7) at 12 weeks. Remibrutinib met all primary endpoints, with improvements in UAS7, ISS7, and HSS7.2

The remibrutinib arm had a significantly greater reduction in the UAS7 at week 12 than the placebo arm (least-squares mean [±SE] change, −20.0±0.7 vs. −13.8±1.0; P <.001] in REMIX-1 and −19.4±0.7 vs. −11.7±0.9; P <.001 in REMIX-2).4 Moreover, significantly more participants in the remibrutinib group than the placebo group had a UAS7 of ≤ 6 (REMIX-1, 49.8% vs. 24.8%, P <.001; REMIX-2, 46.8% vs. 19.6%, P <.001) and a UAS7 of 0 (REMIX-1, 31.1% vs. 10.5%, P <.001; REMIX-2, 27.9% vs. 6.5%, P <.001).

Participants initially in the placebo arm who switched to remibrutinib at the 24-week mark demonstrated rapid and sustained symptom improvements during the first week after the switch.2 The study found that nearly half were able to get complete relief from hives (UAS7 = 0) by 52 weeks.

The trials demonstrated that remibrutinib was well-tolerated, with a safety profile similar to that of the placebo at 24 weeks, in terms of both adverse events and serious adverse events. The study did not link any serious adverse events to remibrutinib.2

Common adverse events included respiratory infections and headaches. Participants in both arms had similar lung function, and any transaminase elevations were asymptomatic, temporary, and reversible.2

Moving forward, investigators are evaluating remibrutinib for other indications, including chronic inducible urticaria, hidradenitis suppurativa, food allergies, and multiple sclerosis.2

"The approval of remibrutinib is an important development in CSU care," said REMIX trial investigator Giselle Mosnaim, MD, an allergist and immunologist from Endeavor Health and clinical associate professor at the University of Chicago Pritzker School of Medicine. "It quickly reduces symptoms, offering patients control of the hives and itching that they experience on a daily basis. This is significant because it expands beyond existing injectable treatments and gives patients an oral option that can easily be incorporated into their daily lives.”

References

1. Novartis Pharma AG. Novartis receives FDA approval for Rhapsido® (remibrutinib), the only oral, targeted BTKi treatment for chronic spontaneous urticaria (CSU). GlobeNewswire News Room. Published September 30, 2025. Accessed September 30, 2025. https://www.globenewswire.com/news-release/2025/09/30/3159065/0/en/Novartis-receives-FDA-approval-for-Rhapsido-remibrutinib-the-only-oral-targeted-BTKi-treatment-for-chronic-spontaneous-urticaria-CSU.html

2. Novartis Phase III data confirm sustained efficacy and long-term safety of oral remibrutinib in chronic spontaneous urticaria. Novartis. https://www.novartis.com/news/media-releases/novartis-phase-iii-data-confirm-sustained-efficacy-and-long-term-safety-oral-remibrutinib-chronic-spontaneous-urticaria

3. Smith T. New Long-Term Findings Confirm Safety, Efficacy of Oral Remibrutinib for CSU. HCPLive. Published June 3, 2024. Accessed September 22, 2025. https://www.hcplive.com/view/new-long-term-findings-confirm-safety-efficacy-of-oral-remibrutinib-for-csu

4. Metz M, Giménez-Arnau A, Hide M, et al. Remibrutinib in Chronic Spontaneous Urticaria. N Engl J Med. 2025;392(10):984-994. doi:10.1056/NEJMoa2408792