Add-on remibrutinib improved urticaria control as early as Week 2, with improvements sustained through Week 52, according to long-term results from the REMIX-1/-2 Phase 3 trials presented at the 2025 American Academy of Allergy Asthma and Immunology (AAAAI) meeting in San Diego, CA..
Novartis’ remibrutinib is a selective Bruton’s tyrosine kinase (BTK) inhibitor under investigation in chronic spontaneous urticaria (CSU).
The Dermatology Digest has been closely following the development of remibrutinib. We sat down with study author Martin Metz, MD, a Professor of Dermatology at Charité – Universitätsmedizin in Berlin, Germany, to discuss the recently released results of the REMIX-1/-2 Phase 3 trials and the new thinking about diagnosing and treating CSU and other types of urticaria such as chronic inducible urticaria (CIndU).
TDD: Please share some of the topline results from the REMIX-1/-2 Phase 3 Trials that were presented at the recent AAAAI meeting.
Dr. Metz: The REMIX-1/-2 trials tell us that we will have a new effective treatment for patients with CSU. We only have omalizumab (Xolair, Genentech & Novartis), which is a good drug but only works in a certain number of CSU patients. Remibrutinib has a very fast onset of response and a high rate of efficacy in CSU patients. We also showed efficacy in patients who previously did not respond to omalizumab. REMIX-1/-2 are identical, multicenter, randomized, double-blind, placebo-controlled Phase 3 trials assessing the efficacy and safety of remibrutinib in patients with CSU remaining symptomatic despite second-generation H1-antihistamines. Patients were randomized 2:1 to add-on remibrutinib 25mg twice daily (bid), or placebo. At Week 24, all patients received an add-on open-label remibrutinib 25mg bid until Week 52. Urticaria control was assessed using the weekly urticaria control test (UCT7) at baseline and weeks 2, 4, 12, 24, and 52.
Overall, 912 patients were included in the full analysis set (remibrutinib [N=606]; placebo [N=306]). Remibrutinib showed fast improvement in mean change from baseline in the UCT7 vs. placebo at Week 2 (REMIX-1: 5.74 vs. 1.95; REMIX-2: 5.57 vs. 2.27) and Week 24 (REMIX-1: 7.17 vs. 4.60; REMIX-2: 6.93 versus 4.47), which was sustained through Week 52. The proportion of patients with UCT7≥12 (well-controlled urticaria) was higher at Week 24 with remibrutinib vs. placebo (REMIX-1: 63.1% vs. 41.6%; REMIX-2: 64.8% vs. 40.2%), with similar proportions observed at Week 52. Patients transitioning from placebo to remibrutinib at Week 24 experienced similar improvements through Week 52.”
TDD: How does remibrutinib work?
Dr. Metz: “It’s a new mode of action for urticaria. Remibrutinib is a small molecule oral agent that inhibits BTK, a signal transduction molecule that is downstream of IgE receptors. These receptors get crosslinked and activated through BTK, but remibrutinib inhibits BTK and therefore prevents the activation of mast cells through IgE.”
TDD: What other remibrutinib trials are ongoing in CSU?
Dr. Metz: “There are other ongoing large Phase 3 studies. One study is looking at how remibrutinib works in adolescents with CSU, and other trials are ongoing in every kind of urticaria.”
TDD: How can dermatologists better diagnose CSU or other types of urticaria?
Dr. Metz: “My recommendation is very simple. CSU is not a difficult disease to diagnose and manage. Don’t be afraid. It is all about symptom treatment. If antihistamines don’t work, step up to omalizumab. If this doesn’t work, in the future, we may have remibrutinib or dupilumab (Dupixent, Sanofi & Regeneron). Treat the symptoms. There is no lab screening for CSU.
For CIndU, we need to confirm the respective trigger with provocation tests. If it is possibly cold urticaria, we will use ice in a bag with water on the skin, and if positive. It’s cold urticaria. For dermographism urticaria, we scratch the skin.”
