Chronic Spontaneous Urticaria (CSU) is a distressing condition characterized by the spontaneous appearance of itchy wheals and angioedema, persisting for six weeks or longer. For many patients, the struggle to manage symptoms remains challenging despite the use of H1-antihistamines. However, recent advancements offer new hope. At the EAACI 2024 meeting in Valencia, Spain, groundbreaking data was presented on several promising new compounds. In this article, we share some of the latest developments.

Long-term efficacy and safety of remibrutinib for CSU: Promising phase III study results

Recent findings from the phase III REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) studies highlight the long-term efficacy and safety of remibrutinib, a novel oral Bruton’s tyrosine kinase inhibitor, for patients suffering from CSU.

The REMIX-1 and REMIX-2 studies are multicenter, randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of remibrutinib in CSU patients inadequately controlled with H1-antihistamines. Participants were randomized 2:1 to receive 25 mg of oral remibrutinib twice daily or a placebo for 24 weeks, followed by 28 weeks of open-label remibrutinib. The primary endpoints assessed changes from baseline in weekly Urticaria Activity Score (UAS7) and weekly Itch and Hives Severity Scores (ISS7 and HSS7) at week 12, while secondary outcomes included the proportion of patients achieving UAS7=0 and UAS7≤6 at weeks 2 and 12, and the occurrence of adverse events, with all endpoints reassessed at weeks 24 and 52.

The studies included 313 and 300 patients in the remibrutinib groups and 157 and 155 in the placebo groups for REMIX-1 and REMIX-2, respectively. At week 12, remibrutinib demonstrated superior improvements in UAS7, ISS7 and HSS7 scores compared to placebo, with these benefits sustained through week 24. Notably, by week 2, significant improvements in UAS7≤6 rates were observed with remibrutinib, and by week 12, more patients achieved UAS7≤6 and UAS7=0 compared to placebo. Remibrutinib was well tolerated across both studies, with an adverse event profile similar to that of the placebo group.

As we anticipate the presentation of the week 52 data, the future looks promising for remibrutinib as a transformative treatment option for CSU.

TAS5315 gives further hope for patients not responded adequately to H1-antihistamines

A randomized, double-blind, placebo-controlled phase IIa trial (NCT05335499), investigated the efficacy and safety of TAS5315, a novel covalent inhibitor of Bruton’s tyrosine kinase (BTK), shows promise for patients with CSI unresponsive to standard H1-antihistamine treatment. 

After a two-week placebo lead-in period, 126 patients were randomized to receive varying doses of TAS5315 (4mg, 2mg, 1mg, 0.5mg, 0.25mg) or placebo for 12 weeks. The primary endpoint was the change from baseline in the weekly urticaria activity score (UAS7) at week 12, analyzed using a mixed-effects model for repeated measures.

Out of the initial cohort, 113 patients completed the study according to protocol. The least squares mean changes from baseline in UAS7 at week 12 were as follows: TAS5315 4mg: -17.15, TAS5315 2mg: -16.01, TAS5315 1mg: -15.19, TAS5315 0.5mg: -11.63, TAS5315 0.25mg: -17.84, and placebo: -9.06. Notably, the 4mg, 2mg, and 0.25mg doses of TAS5315 demonstrated a clinically significant improvement compared to placebo, with changes of -8.09 (p=0.016), -6.95 (p=0.034), and -8.78 (p=0.008), respectively. TAS5315 was well tolerated across all doses, with all adverse events (AEs) being mild or moderate.

These preliminary results show a trend towards dose-response relationship, but further studies are needed to explore the long-term safety and efficacy of TAS5315 in this patient population.

Barzolvolimab Shows Promising Results in Improving Angioedema for patients with CSU

A recent phase II clinical trial (NCT05368285) has revealed significant improvements in angioedema symptoms for patients suffering from CSU who were treated with barzolvolimab. The double-blind, placebo-controlled trial enrolled 208 patients who were randomized to receive barzolvolimab at varying doses (75mg, 150mg, and 300mg) or a placebo. The study consisted of a 16-week placebo-controlled treatment phase, followed by 36 weeks of active treatment and a 24-week follow-up period. The primary endpoint was the mean change in urticaria activity score (UAS7) at Week 12, while secondary and exploratory endpoints included changes in the angioedema activity score (AAS7) and the number of angioedema-free days (AFD).

Of the 208 patients, 149 had an AAS7 greater than 0 at baseline, indicating the presence of angioedema. At Week 12, patients receiving barzolvolimab showed significant improvements in their AAS7 scores compared to those receiving the placebo. Specifically, the least square mean changes in AAS7 from baseline were -33.6 for the 75mg group, -39.6 for the 150mg group, and -41.4 for the 300mg group, compared to -16.0 for the placebo group. These improvements were statistically significant, with p-values of 0.0039, <0.0001 and <0.0001, respectively.

Additionally, the proportion of patients experiencing an improvement of 8 or more points in AAS7 was notably higher in the barzolvolimab groups (82.9%, 87.1% and 85.0% for the 75mg, 150mg and 300mg groups, respectively) compared to the placebo group (57.1%).

The mean number of angioedema-free days from the start of treatment to Week 12 also favoured barzolvolimab, with patients in the 75mg, 150mg, and 300mg groups reporting 54.1, 64.1 and 68.8 days free of angioedema, respectively, versus 56.3 days in the placebo group.

The phase 2 trial concluded that barzolvolimab significantly improves angioedema and overall CSU symptoms, meeting its primary endpoint and demonstrating a favourable safety profile. With these promising results from the Phase 2 trial, we eagerly await further development and data.

Disclosures: This article was created by the touchDERMATOLOGY team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.

Take a look at recent articles, conference highlights and education on urticaria.