The FDA recently approved remibrutinib (Rhapsido, Novartis), the first and only oral, targeted Bruton’s tyrosine kinase inhibitor (BTKi) for adult patients with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1-antihistamine therapy. This approval represents a significant advancement in CSU management, offering patients a convenient oral alternative to existing injectable options.
Mechanism of Action
Remibrutinib selectively inhibits BTK, a signaling protein that mediates activation of immune cells such as mast cells and basophils. In CSU, overactivation of these cells leads to histamine release and a cascade of inflammatory signaling. By blocking BTK activity, remibrutinib disrupts this immune pathway, helping to reduce the frequency and intensity of hives and itch.
Clinical Findings
The approval is based on results from the phase 3 REMIX trials, which demonstrated:
- Significant improvement in weekly itch scores versus placebo
- Well-controlled disease achieved as early as week 2
- Complete absence of itch and hives by week 12 in approximately one-third of patients treated
- Sustained efficacy with continued treatment in long-term, open-label extensions
Remibrutinib also demonstrated a favorable safety profile, with the most commonly reported adverse events being nasopharyngitis, headache, minor bleeding, nausea, sore throat, and abdominal pain.
A New Option for an Ongoing Challenge
CSU symptoms have a profound impact on quality of life, disrupting sleep, work, and overall well-being of the 1.7 million people in the U.S. living with the condition. While antihistamines remain the first-line therapy, more than half of patients continue to experience symptoms even at higher doses. For those who do not respond, injectable biologic therapies have been the next step, yet fewer than 20% of eligible patients receive them.
“The approval of remibrutinib is an important development in CSU care,” 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. “It quickly reduces symptoms, offering patients control of the hives and itching that they experience on a daily basis.”
Offering New Hope
Mark Lebwohl, MD, dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai, and member of the REMIX phase 3 steering committee, described the FDA approval of remibrutinib as “exciting news,” noting that an oral option offers new hope for patients who have not responded to antihistamines.
“It is also a very fast-acting medication,” he added, “which poses a major advantage for our patients.”
Dr. Lebwohl emphasized the challenges of diagnosing and managing CSU:
“It’s difficult to diagnose and manage. 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.”
Looking Ahead
For patients affected by CSU, this new oral therapy offers an alternative that may be easier to integrate into daily life.
Victor Bultó, president of U.S. Novartis, calls the approval of Rhapsido an important milestone in advancing care for overlooked immune-related conditions like CSU.
“Building on our legacy in advancing the treatment of allergic, dermatologic, and rheumatologic conditions, we are deeply committed to further investing in innovative, patient-focused therapies across immunology.”
Remibrutinib’s mechanism is also being explored in ongoing clinical trials for other immune-mediated diseases, including chronic inducible urticaria (CIndU), hidradenitis suppurativa (HS), and food allergy.
It’s an exciting development not just for CSU patients, but also for those who suffer from related conditions.
