Safety and Efficacy Updates for Asthma and Urticaria Therapies

The long-term safety and efficacy of omalizumab, alongside promising phase 3 trial results that demonstrated the efficacy and favorable hematological safety profile of remibrutinib, were highlighted at the 2025 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress. | Image Credit: Сергей Шиманович - stock.adobe.com

New treatments for allergy and related inflammatory conditions focus on the safety and efficacy of novel and existing therapies for chronic spontaneous urticaria (CSU) and severe allergic asthma. Research from the 2025 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress highlights recent advancements in the understanding and management of allergic diseases and chronic urticaria.1-3

Long-Term Safety and Efficacy of Omalizumab

The FDA has approved omalizumab, a recombinant humanized monoclonal antibody against immunoglobulin E (IgE), for patients with severe allergic asthma, severe CSU, and chronic rhinosinusitis with nasal polyps.4 Researchers conducted a study at a tertiary clinic where they administered omalizumab to adult patients with asthma (IgE levels, 30-700 IU/L) and adolescent patients (IgE levels, 30-1300 IU/L). Physicians administered omalizumab to patients with severe CSU if they did not respond to conventional H1-antihistamines at 3 to 4 times the suggested dose or if they depended on oral steroids.

Patients with asthma underwent spirometry testing every 3 months, and patients with CSU reported scores for the Urticaria Activity Score over 7 days tool every 6 months. Researchers administered more than 2.5 million omalizumab injections in the past 2 decades without any reported anaphylaxis or serum sickness requiring medical intervention. Omalizumab demonstrated a high level of safety and efficacy with virtually no risk of anaphylaxis or serum sickness.

Remibrutinib Improves Urticaria Control

Remibrutinib, a novel, highly sensitive, oral Bruton tyrosine kinase inhibitor, demonstrated superior efficacy vs placebo in patients with CSU in the REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) phase 3 trials.2 The identical, multicenter, randomized, double-blind, placebo-controlled REMIX-1/-2 phase 3 trials assessed the efficacy and safety of remibrutinib in patients with CSU who remained symptomatic despite second-generation H1-antihistamines. Researchers randomized patients in a 2 to 1 ratio to receive add-on remibrutinib 25 mg twice daily or placebo. All patients received add-on open-label remibrutinib 25 mg twice daily from week 24 until week 52. Researchers assessed urticaria control using the weekly Urticaria Control Test (UCT7) at baseline and weeks 2, 4, 12, 24, and 52.

The study included a total of 912 patients, and researchers administered remibrutinib to 606 patients and a placebo to 306 patients. By week 2, remibrutinib rapidly improved the mean change from baseline in UCT7 compared with placebo (REMIX-1, 5.74 vs 1.95; REMIX-2, 5.57 vs 2.27), and this improvement remained well sustained through week 52 (REMIX-1, 7.17 vs 4.6 at week 24; REMIX-2, 6.93 vs 4.47 at week 24).

A higher percentage of patients achieved a UCT of 12 or greater (considered well-controlled) 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 who transitioned from placebo to remibrutinib at week 24 experienced similar improvements through week 52. The REMIX-1/-2 studies demonstrated improved urticaria control with add-on remibrutinib as early as week 2, with improvements remaining through week 52.

Hematological Safety Profile of Remibrutinib

Researchers analyzed the change from baseline in mean blood cell counts from the pooled REMIX-1 and REMIX-2 studies.3 Patients received remibrutinib 25 mg twice daily or a placebo for 24 weeks and then received remibrutinib 25 mg twice daily from week 24 to week 52.

The mean difference of change from baseline between remibrutinib and placebo in mean blood cell counts at week 24 showed the following: basophils (0.004), eosinophils (0.000), neutrophils (–0.199), erythrocytes (–0.022), leukocytes (–0.122), lymphocytes (0.048), monocytes (0.009), and platelets (–23.134).

Researchers highlighted that notable decreases were single instances and mostly transient. Researchers found no clinically meaningful trends during open-label treatment with remibrutinib for up to 52 weeks. Remibrutinib treatment did not cause a clinically substantial change in mean blood cell counts, which is consistent with the favorable clinical safety profile observed in phase 3 studies.

These posters underscore ongoing progress in managing severe allergic conditions and chronic urticaria through the sustained safety and efficacy of established biologics like omalizumab and the promising clinical profile of novel therapies such as remibrutinib.1-3

References

1. Santucci S, Yang W, Comiskey A, et al. Observed incidence of anaphylaxis and serum sickness in patients receiving omalizumab in a Canadian tertiary allergy/asthma clinic: an update. Presented at: 2025 AAAAI/WAO Joint Congress; February 28-March 3, 2025; San Diego, CA. Poster 055.

2. Metz M, Bin Y, Boren E, et al. The impact of remibrutinib on urticaria control in patients with chronic spontaneous urticaria: long-term results from the REMIX-1/-2 phase 3 trials. Presented at: 2025 AAAAI/WAO Joint Congress; February 28-March 3, 2025; San Diego, CA. Poster 551.

3. Mosnaim G, Windom H, Xinghua G, et al. Remibrutinib treatment has no clinical impact on mean blood cell counts in patients with chronic spontaneous urticaria: pooled safety analysis from REMIX-1 and REMIX-2 studies. Presented at: 2025 AAAAI/WAO Joint Congress; February 28-March 3, 2025; San Diego, CA. Poster 592.

4. FDA approves first medication to help reduce allergic reactions to multiple foods after accidental exposure. FDA. News release. February 16, 2024. Accessed April 4, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-help-reduce-allergic-reactions-multiple-foods-after-accidental