Rilzabrutinib Yields Responses in Angioedema in People With CS Urticaria

Jonathan Bernstein, MD,

Credit: University of Cincinnati School of Medicine

Participants with moderate-to-severe chronic spontaneous urticaria (CSU) and angioedema treated with 1200mg of rilzabrutinib a day had greater improvements in their angioedema than those treated with placebo.¹

These findings, from the phase 2 RILECSU trial (NCT05107115), will be presented at the 2025 American Academy of Allergy, Asthma, and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress, February 28-March 3, in San Diego, California, by Jonathan Bernstein, MD, adjunct professor, University of Cincinnati School of Medicine and past president of the AAAAI.

“Many patients with CSU experience angioedema, a rapid, potentially life-threatening swelling of the face and extremities. CSU is an immunological disease mainly driven by activated mast cells in skin. Bruton’s tyrosine kinase (BTK) plays a critical role in multiple immune-mediated disease processes. Rilzabrutinib (SAR444671) is an oral reversible covalent BTK inhibitor being investigated as a CSU therapy. Here, the effect of rilzabrutinib on angioedema is evaluated,” Bernstein and colleagues wrote.¹

RILECSU is a 52-week Phase 2 study that consists of a 12-week, randomized, double-blind, placebo-controlled, dose-ranging efficacy and safety period and a 40-week open-label extension period. The study enrolled 160 adults with moderate-to-severe CSU whose disease was not adequately controlled with H1-antihistamines alone. The participants were randomized 1:1:1:1 to rilzabrutinib 1200mg a day, 800mg a day, 400mg a day or placebo. Bernstein and colleagues investigated the effect of rilzabrutinib on angioedema in 102 out of 143 participants who had not previously received omalizumab and had weekly Angioedema Activity Score (AAS7) of over 0 at baseline.¹

The investigators found that at Week 12, a higher proportion of participants on rilzabrutinib 1200mg a day (60.9%) achieved AAS7 scores of 0 than placebo-treated participants (30.8%). Improvements were rapid, with 30.4% of participants on rilzabrutinib 1200mg a day reaching AAS7 scores of 0 at Week 1 compared with 3.8% of those on placebo. The proportion of participants with AAS7 scores of 0 was numerically higher every week through week 12 with rilzabrutinib 1200mg a day than with placebo. The duration of AAS7 0 response up to 12 weeks was greater with rilzabrutinib 1200mg a day (5.1 weeks) than with placebo (3.1 weeks).¹

Bernstein is also giving a talk on emerging treatment approaches for angioedema in patients with urticaria at the AAAAI/WAO meeting.² He spoke with HCPLive® about forthcoming research and unmet needs that remain in the field, including addressing the significant burden on patients with inflammatory skin conditions such as urticaria and improving their management. He also discussed a need for more physician education and progress in research in the space, including adding to the field’s understanding of the disease, including mast cells mechanisms.

“I think that's really the biggest thing that's confronting us, is to get clinicians understand the spectrum of angioedema and to make sure that they aren't skipping steps and going from inexpensive antihistamines to extremely expensive drugs that are targeted towards hereditary angioedema,” Bernstein told HCPLive in an interview.

REFERENCES

1. Bernstein J, Lee CH, Ferrucci S, et al. Effects of Rilzabrutinib on Angioedema over 12 Weeks: Results from the Phase 2 RILECSU Trial in Participants With Moderate-to-Severe Chronic Spontaneous Urticaria. Presented at: 2025 AAAAI/WAO Joint Congress, February 28-March 3. Abstract 192.

2. Bernstein J. Emerging Treatment Approaches to Hives, Itch, and Angioedema. Presented at: 2025 AAAAI/WAO Joint Congress, February 28-March 3.