FDA Approves Remibrutinib, First Oral BTK Inhibitor for CSU

The US Food and Drug Administration (FDA) has approved remibrutinib (Rhapsido; Novartis), an oral Bruton’s tyrosine kinase inhibitor (BTKi), for the treatment of adult patients with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1-antihistamine therapy. This marks the first approval of a BTKi for CSU and introduces a novel oral option for patients whose symptoms are not adequately controlled with standard antihistamines.¹

"Patients with CSU now have a game-changing oral therapy that provides a high degree of efficacy and safety. Importantly, based on the REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) trials patients can also expect relatively quick onset of action, which will provide much needed symptom relief to patients struggling with CSU," Christopher Bunick, MD, PhD, associate professor of dermatology at the Yale School of Medicine and editor in chief of Dermatology Times said. "The mechanism by which remibrutinib selectively targets BTK is elegant, and reimagines what is possible in managing mast cell-related disorders."

Mechanism of Action

Remibrutinib is a highly selective inhibitor of BTK, a signaling protein that plays a critical role in immune cell activation. In CSU, BTK activation contributes to the release of histamine and other inflammatory mediators from mast cells and basophils.² By blocking BTK activity, remibrutinib aims to reduce this cascade and mitigate symptoms.

Beyond symptom control, emerging data suggest BTK inhibition may influence the autoimmune mechanisms underlying type IIb autoimmune CSU. At the European Academy of Dermatology and Venereology (EADV) Congress 2025, investigators reported that remibrutinib reduced serum levels of autoantibodies against FcεRI and thyroid antigens, particularly in patients with positive Chronic Urticaria Index (CUI) tests. These findings suggest potential immunomodulatory effects in a subset of patients, though whether such changes alter the long-term disease course remains under investigation.³

Clinical Trial Evidence

The FDA approval is supported by the phase 3 REMIX-1 and REMIX-2 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 included:

• 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.
• Approximately one-third of treated patients reported complete absence of itch and hives by week 12.
• Improvements were sustained through longer-term treatment in open-label extensions.

Remibrutinib demonstrated a favorable safety profile requiring no laboratory monitoring. The most common adverse events (≥3%) were nasopharyngitis, headache, bleeding, nausea, sore throat, and abdominal pain.

Clinical and Patient Perspectives

Experts have highlighted the significance of an oral, non-injectable option in this disease setting. Mark Lebwohl, MD, of the Icahn School of Medicine, noted that remibrutinib blocks a central pathway in CSU immune activation, providing a new therapeutic avenue. “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, said in a news release. “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.”

Walter Liszewski, MD, assistant professor of dermatology and an assistant professor of cancer epidemiology at Northwestern University, told Dermatology Times, "As someone who specializes in itchy rashes, a major part of my job is CSU, and I am so excited that we have approval for remibrutinib. I think the field of chronic urticaria is going to be completely changed. I'm excited to not only use this drug for my patients, but to get other dermatologists really excited about taking chronic urticaria back."

Patient advocacy groups also welcomed the approval. According to Lynda Mitchell of the Allergy & Asthma Network, many patients feel underserved by current therapies and may benefit from having a convenient oral alternative.

Broader Implications

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 is pursuing regulatory review in multiple regions, including Europe, Japan, and China. Ongoing studies are also evaluating remibrutinib in 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.

Background on CSU and Unmet Need

CSU is a mast cell-driven condition defined by recurrent hives, angioedema, or both for more than 6 weeks without identifiable triggers. The disease is thought to arise from immune dysregulation, including both IgE-mediated allergic pathways and IgG-mediated autoimmune pathways. Activation of mast cells and basophils triggers the release of histamine and other proinflammatory mediators, leading to symptoms such as swelling, itching, and wheals.

CSU significantly impairs quality of life, affecting sleep, work productivity, and mental health. Diagnosis may be delayed for up to 2 years, and more than half of patients remain symptomatic despite high-dose antihistamines. 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.

References

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 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. Bernstein JA, Maurer M, Saini SS. BTK signaling-a crucial link in the pathophysiology of chronic spontaneous urticaria. J Allergy Clin Immunol. 2024;153(5):1229-1240. doi:10.1016/j.jaci.2023.12.008
3. Metz M. Remibrutinib decreases specific IgG autoantibody levels in patients with chronic spontaneous urticaria. Presented at: European Academy of Dermatology and Venereology Congress 2025; September 17-20, 2025; Paris, France.