Written By: Pallavi Sahane BPharm
Reviewed By: Pharmacally Editorial Team
On 30 September 2025, The United States Food and Drug Administration (FDA) has granted approval to Rhapsido® (remibrutinib), developed by Novartis AG, for the treatment of chronic spontaneous urticaria (CSU) in adults who continue to have symptoms even after using H1 antihistamines.
Rhapsido is an oral tablet taken twice daily. It does not require injections or routine laboratory monitoring, which makes it convenient for patients and easier to prescribe for physicians. This approval makes Rhapsido the first and only Bruton’s tyrosine kinase inhibitor (BTKi) approved for CSU.
About Rhapsido
Remibrutinib is a selective oral inhibitor of Bruton’s tyrosine kinase (BTK), a key signaling protein found in immune cells such as mast cells and basophils. These cells are responsible for releasing substances like histamine, which trigger the itching, redness, swelling, and flare-ups seen in chronic spontaneous urticaria (CSU). By blocking BTK, remibrutinib interrupts this chain of reactions, thereby reducing the release of inflammatory chemicals that drive CSU symptoms. It is formulated as an oral tablet, taken twice daily, making it a practical and convenient treatment option compared to injectables. As the first oral BTK inhibitor approved for CSU, remibrutinib offers a valuable alternative for patients whose symptoms remain uncontrolled with existing therapies like anti histamines.
About Chronic Spontaneous Urticaria (CSU)
Chronic spontaneous urticaria (CSU) is a skin condition marked by recurrent hives, itching, and sometimes swelling (angioedema) that occur without a clear external trigger. It is diagnosed when symptoms persist for more than six weeks and affects an estimated 0.5% to 1% of the global population at any given time. The disease is unpredictable, with flare-ups that can significantly disrupt sleep, daily activities, and overall quality of life. Current treatment begins with non-sedating H1 antihistamines, but many patients continue to experience symptoms even when doses are increased. For those who do not respond, omalizumab, an anti-IgE monoclonal antibody administered by injection, is considered as the next option. However, despite these available treatments, more than half of CSU patients remain inadequately controlled. Rhapsido provides an important new oral treatment alternative for patients, whose symptoms remain uncontrolled with existing medications, offering a practical and accessible option.
Clinical Evidence
The FDA approval of Rhapsido® (remibrutinib) was based on results from two pivotal Phase III clinical trials, REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157), which evaluated its efficacy and safety in adults with chronic spontaneous urticaria who continued to experience symptoms despite treatment with second-generation H1 antihistamines. Both trials were randomized, double-blind, placebo-controlled studies. Patients were assigned to receive either remibrutinib or placebo for a treatment period of 12 weeks, with primary and secondary endpoints measuring improvement in urticaria activity. The primary endpoint was the change from baseline in the weekly Urticaria Activity Score (UAS7) at Week 12, which reflects the combined severity of itching and hives.
Results showed that patients receiving remibrutinib had significantly greater reductions in UAS7 scores compared with those on placebo. Secondary outcomes, including weekly itch severity score (ISS7) and weekly hive severity score (HSS7), also demonstrated marked improvement with remibrutinib. Importantly, some patients reported symptom relief as early as Week 2, highlighting the rapid onset of action. By Week 12, approximately one-third of patients treated with remibrutinib achieved complete absence of hives and itching, and a significantly higher proportion reached well-controlled disease status (UAS7 ≤6) compared to placebo. Together, these findings confirm that remibrutinib offers both effective and fast-acting relief for CSU patients who remain symptomatic despite standard therapies.
Safety profile
The safety profile of Rhapsido® (remibrutinib) was found to be favorable in clinical trials, with most side effects reported as mild to moderate. The most common adverse events, occurring in at least 3% of patients, included headache, nausea, abdominal pain, nasopharyngitis (sore throat and runny nose), and mild bleeding events. Patients may need to pause therapy for three to seven days before and after planned surgical procedures, and caution should be taken in individuals using blood thinners, those with liver problems, or women who are pregnant or planning to become pregnant. The safety of remibrutinib during pregnancy and breastfeeding has not yet been established, and the use of live or live-attenuated vaccines should be avoided during treatment. Overall, the trials confirmed that remibrutinib has no new or unexpected safety concerns.
Key Opinions
Experts have highlighted the significance of Rhapsido® (remibrutinib) as a new treatment option for chronic spontaneous urticaria. Dr. Mark Lebwohl, a REMIX trial investigator from the Icahn School of Medicine at Mount Sinai, noted that remibrutinib represents a novel approach by blocking BTK, an important immune pathway, thereby offering fast relief for many patients. Lynda Mitchell, CEO of the Allergy & Asthma Network, emphasized the patient perspective, pointing out that many individuals with CSU feel misunderstood and inadequately treated, and welcomed the convenience of an oral therapy that offers new hope for those struggling daily with the condition. Victor Bultó, President of Novartis US, described the FDA approval as a milestone in CSU treatment and underscored the company’s broader commitment to reshaping care for immune-related diseases with innovative, patient-focused therapies.
References
Novartis receives FDA approval for Rhapsido® (remibrutinib), the only oral, targeted BTKi treatment for chronic spontaneous urticaria (CSU), Novartis, 30 September 2025, https://www.novartis.com/us-en/news/media-releases/novartis-receives-fda-approval-rhapsido-remibrutinib-only-oral-targeted-btki-treatment-chronic-spontaneous-urticaria-csu
Metz M, Giménez-Arnau A, Hide M, Remibrutinib in Chronic Spontaneous Urticaria. N Engl J Med. 2025 Mar 6; 392(10):984-994. Doi: 10.1056/NEJMoa2408792. PMID: 40043237.
A Phase 3 Study of Efficacy and Safety of Remibrutinib in the Treatment of CSU in Adults Inadequately Controlled by H1 Antihistamines (REMIX-1), ClinicalTrials.gov ID NCT05030311, https://clinicaltrials.gov/study/NCT05030311
A Phase 3 Study of Efficacy and Safety of Remibrutinib in the Treatment of CSU in Adults Inadequately Controlled by H1-antihistamines (REMIX-2), ClinicalTrials.gov ID NCT05032157, https://clinicaltrials.gov/study/NCT05032157
Highlights of Prescribing Information, RHAPSIDO® (remibrutinib) tablets, for oral use, Novartis, https://www.novartis.com/us-en/sites/novartis_us/files/rhapsido.pdf