Novartis' Oral Targeted BTKi Treatment Approved for Chronic Spontaneous Urticaria in Adults

The FDA approved remibrutinib (Rhapsido; Novartis), the first oral Bruton’s tyrosine kinase inhibitor (BTKi) for adults with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1-antihistamine treatment. The announcement, from Novartis, was made on October 1, 2025, World Urticaria Day.

CSU is an inflammatory skin condition characterized by recurrent wheals, angioedema, or both lasting more than 6 weeks. Mast cells and basophils drive the disease through histamine and cytokine release. Two main autoimmune mechanisms are implicated: type I autoimmunity (autoallergy) mediated by IgE against autoallergens, and type IIb autoimmunity mediated by IgG against the IgE receptor (FcεRI) or receptor-bound IgE. These pathways may overlap in individual patients.4

In CSU, BTK activation drives mediator release and is believed to support autoantibody production. Inhibiting BTK interrupts signaling from FcεRI and reduces degranulation, histamine/cytokine release, and downstream inflammation. Because BTK plays a shared role in both effector cell activation and adaptive autoimmunity, BTK inhibition offers a dual mechanism of action in treating CSU.

“CSU is a serious disease that can cause debilitating symptoms and unpredictable flares. It’s difficult to diagnose and manage,” 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, said 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.”

REMIX-1 and REMIX-2 Phase 3 Trials

The FDA based its approval on data from the phase 3 REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) clinical trials. Remibrutinib demonstrated superiority over placebo in reducing itch (ISS7), hives (HSS7), and Urticaria Activity Score over 7 days (UAS7) at 12 weeks. Metz Significantly more participants achieved well-controlled disease (UAS7 of 6 or less) as early as week 2, and about one-third reported complete absence of itch and hives at week 12. The most common adverse events (incidence of 3% or more) included nasopharyngitis, bleeding, headache, nausea, and abdominal pain.

CSU diagnosis can take up to 24 months, and more than half of patients continue to experience symptoms even at high doses of antihistamines, according to Novartis. Many patients also live with asthma, allergies, or other immune-related conditions, and CSU significantly affects sleep, work productivity, and mental health. “Roughly 1 in 5 people will experience hives at some point in their lives, and over 3 million people in the US. will experience chronic hives,” Kenneth Mendez, president and CEO of the Asthma and Allergy Foundation of America (AAFA), said in a separate statement.

“We know that for many patients, urticaria is part of a bigger picture of immune system dysfunction. Recognizing UDAY as a community helps ensure that no one is left behind, and that together we can advocate for expanded research, clinical awareness, and comprehensive care,” Jessica Fraser, executive director of The Mast Cell Disease Society, added in the Novartis statement.

Novartis has submitted remibrutinib for regulatory review in the European Union, Japan, and China, with priority review granted in China, the company stated. Remibrutinib is also being studied in in chronic inducible urticaria, food allergy, and hidradenitis suppurativa.

1. Novartis receives FDA approval for Rhapsido® (remibrutinib), the only oral, targeted BTKi treatment for chronic spontaneous urticaria (CSU). News release. Novartis. September 30, 2025. Accessed October 2, 2025. https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-rhapsido-remibrutinib-only-oral-targeted-btki-treatment-chronic-spontaneous-urticaria-csu
2. Metz M, Giménez-Arnau A, Hide M, et al. Long-term efficacy and safety of remibrutinib in patients with chronic spontaneous urticaria in the Phase 3 REMIX-1 and REMIX-2 studies. Presented as a late oral abstract session on clinical trials at EAACI 2024; May 31-June 3, 2024; Valencia, Spain.