The US Food and Drug Administration has approved remibrutinib (Rhapsido; Novartis), marking a significant milestone as the first oral Bruton's tyrosine kinase inhibitor (BTKi) approved for chronic spontaneous urticaria (CSU). The approval provides adult patients who remain symptomatic despite H1-antihistamine therapy with a novel oral treatment option that requires no laboratory monitoring.
Novel Mechanism Targets Immune Pathway
Remibrutinib operates as a highly selective inhibitor of BTK, a signaling protein critical in immune cell activation. In CSU, BTK activation contributes to the release of histamine and other inflammatory mediators from mast cells and basophils. By blocking BTK activity, remibrutinib aims to reduce this inflammatory cascade and mitigate symptoms.
"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," 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.
Emerging data presented at the European Academy of Dermatology and Venereology Congress 2025 suggest BTK inhibition may influence autoimmune mechanisms underlying type IIb autoimmune CSU. Investigators reported that remibrutinib reduced serum levels of autoantibodies against FcεRI and thyroid antigens, particularly in patients with positive Chronic Urticaria Index tests, though whether such changes alter long-term disease course remains under investigation.
Phase 3 Trial Results Support Efficacy
The FDA approval is supported by the phase 3 REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) trials, which enrolled patients with CSU who remained symptomatic despite antihistamines. Patients were randomized to receive remibrutinib 25 mg twice daily or placebo.
Key findings demonstrated significant improvement versus placebo in weekly itch score (ISS7), hives score (HSS7), and urticaria activity score (UAS7) at week 12. A higher proportion of patients on remibrutinib achieved well-controlled disease (UAS7 ≤6) as early as week 2, with approximately one-third of treated patients reporting complete absence of itch and hives by week 12. Improvements were sustained through longer-term treatment in open-label extensions.
The safety profile proved favorable, requiring no laboratory monitoring. The most common adverse events (≥3%) were nasopharyngitis, headache, bleeding, nausea, sore throat, and abdominal pain.
Addressing Significant Unmet Medical Need
CSU affects an estimated 1.7 million people in the United States and is characterized by recurrent hives, angioedema, or both for more than 6 weeks without identifiable triggers. The condition significantly impairs quality of life, affecting sleep, work productivity, and mental health. Diagnosis may be delayed for up to 24 months, and more than half of patients remain symptomatic despite high-dose antihistamines.
"The approval of remibrutinib is an important development in CSU care. It quickly reduces symptoms, offering patients control of the hives and itching that they experience on a daily basis," said Giselle Mosnaim, MD, MS, an allergist and immunologist from Endeavor Health, clinical associate professor at the University of Chicago Pritzker School of Medicine, and REMIX trial investigator. "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."
Injectable biologic therapies, including omalizumab, are available for refractory cases, but uptake remains limited, with fewer than 20% of eligible patients receiving them. Until now, no oral targeted therapies have been available for this population.
Clinical and Patient Impact
Healthcare professionals have emphasized the significance of having an oral, non-injectable option in this disease setting. Walter Liszewski, MD, assistant professor of dermatology and assistant professor of cancer epidemiology at Northwestern University, expressed enthusiasm about the approval's potential impact on the field of chronic urticaria management.
Patient advocacy groups also welcomed the development. According to Lynda Mitchell, CEO of the Allergy & Asthma Network, "Many CSU patients feel misunderstood and settle for treatments that don't fully meet their needs. We support new treatment options that empower patients to choose what works best for them. This convenient new oral therapy offers a promising new way to manage CSU and potentially improve daily life for those living with this challenging condition."
Broader Development Program
Remibrutinib's approval represents not only a new treatment option for CSU but also the first BTKi authorized for a non-oncologic, immune-mediated dermatologic condition. Novartis has completed regulatory submissions for remibrutinib across multiple countries, including the European Union, Japan, and China, with priority review granted in China.
The company is also investigating remibrutinib in ongoing clinical trials across various immune-related conditions, including chronic inducible urticaria, hidradenitis suppurativa, and food allergy, reflecting broader interest in BTK inhibition across immunology.
While long-term outcomes and potential disease-modifying effects remain to be clarified, the availability of remibrutinib offers a meaningful addition to the CSU treatment landscape, particularly for patients seeking oral therapies after inadequate response to antihistamines.
