Tezepelumab Shows Sustained Post-Treatment Benefit in Chronic Spontaneous Urticaria Despite Missed Primary Endpoint

Research findings presented at the 2025 American Academy of Allergy, Asthma, & Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress in San Diego, California, demonstrate that tezepelumab-ekko (Tezspire; AstraZeneca, Amgen) had post-treatment reductions in chronic spontaneous urticaria (CSU) activity through week 32 of the phase 2b clinical trial, INCEPTION (NCT04833855). The investigators said that although the 16-week primary end point was not met, these data suggest tezepelumab has a delayed, sustained thymic stromal lymphopoietin (TSLP) blockade treatment effect.^1,2

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CSU affects approximately 20% of people at some time during their lives and about 1.4% of the general population at any given time.³

Tezepelumab is a monoclonal antibody that inhibits TSLP. It is an upstream-targeted therapy with the potential to inhibit multiple pathways in CSU, according to the investigators.¹ The agent has also demonstrated efficacy in reducing exacerbations in asthma and chronic obstructive pulmonary disease, as well as chronic rhinosinusitis with nasal polyps.^4-6 Because tezepelumab has been shown to reduce severity or exacerbations of conditions that can be triggered by allergies, the investigators conducted a trial to compare its efficacy, safety, and effect on the improvement of urticaria activity score (UAS7) with omalizumab (Xolair; Novartis Pharmaceuticals), which is currently FDA-approved in patients 12 years and older, and placebo in patients with CSU.^1-3

In INCEPTION (NCT04833855), a randomized, double-blind, placebo-controlled, multicenter, dose-ranging phase 2b trial, a total of 183 patients with CSU were randomly assigned to receive placebo once every 2 weeks, 210 mg of tezepelumab once every 4 weeks, 420 mg of tezepelumab once every 2 weeks, or 300 mg of omalizumab once every 4 weeks for a 16-week treatment duration. Among these patients, 125 were anti-immunoglobulin E (IgE) therapy-naïve, and the other 58 had received anti-IgE therapy. According to the investigators, safety and exploratory end points were evaluated through week 32.^1,2

The findings indicated that the 16-week primary end point was not met. In the overall population, both the 210 and 420 mg doses of tezepelumab did not significantly improve UAS7 when compared with placebo (LSM [SE]: –13.5 [1.6] and –14.7 [1.5], respectively, vs –13.6 [1.6], p = .99, nominal and p = .60, nominal, respectively). Additionally, greater improvement in UAS7 compared with placebo was observed in the anti-IgE-naïve tezepelumab-treated populations. A trend toward significance was also observed with omalizumab, according to the investigators.¹

Further, within the anti-IgE-naïve population, there was delayed, sustained, 32-week off-treatment improvement in UAS7 for those treated with 210 (nominally significant) and 420 mg (trend) of tezepelumab when compared with placebo. This was not observed in patients who received omalizumab. In addition, this effect was larger in patients with lower baseline IgE levels and longer CSU duration and accompanied sustained IL-5 and IL-13 reductions. Overall, tezepelumab and placebo safety findings were balanced, according to the investigators.¹

The authors noted that although the 16-week primary end point was not met, tezepelumab continued to demonstrate post-treatment reductions in CSU activity through week 32. This suggests a delayed, sustained TSLP blockade treatment effect and warrants additional research to further explore or confirm these findings.¹

References

1. McLaren J, Chon Y, Gorski KS, et al. Tezepelumab for the treatment of chronic spontaneous urticaria: Results of the phase 2b INCEPTION study. J Allergy Clin Immunol. 2025. doi:10.1016/j.jaci.2025.01.045
2. Study to evaluate tezepelumab in adults with chronic spontaneous urticaria (INCEPTION). ClinicalTrials.gov identifier: NCT04833855. Updated May 1, 2024. April 13, 2023. https://clinicaltrials.gov/study/NCT04833855
3. American College of Allergy, Asthma, and Immunology. Chronic Spontaneous/Idiopathic Urticaria (Chronic hives). Accessed March 12, 2025. https://acaai.org/allergies/allergic-conditions/skin-allergy/chronic-hives/
4. McGovern G. Tezepelumab reduces exacerbations in patients with severe, Uncontrolled Asthma. Pharmacy Times. July 30, 2024. Accessed March 12, 2025. https://www.pharmacytimes.com/view/tezepelumab-reduces-exacerbations-in-patients-with-severe-uncontrolled-asthma
5. Gallagher A. Study: Tezepelumab reduces annual rates of exacerbations related to COPD. Pharmacy Times. June 5, 2024. Accessed March 12, 2025. https://www.pharmacytimes.com/view/study-tezepelumab-reduces-annual-rates-of-exacerbations-related-to-copd
6. McGovern G. Tezepelumab-Ekko reduces nasal polyp severity and need for surgery in patients with CRSWNP. Pharmacy Times. March 5, 2025. Accessed March 12, 2025. https://www.pharmacytimes.com/view/tezepelumab-ekko-reduces-nasal-polyp-severity-and-need-for-surgery-in-patients-with-crswnp