Rilzabrutinib Reduces Itch, Hives in Chronic Spontaneous Urticaria in Phase 2 Trial


Rilzabrutinib, an oral BTK inhibitor, demonstrates efficacy in reducing itch and disease activity among patients with chronic spontaneous urticaria in phase 2 dose-ranging trial at AAAAI 2024.

Marcus Maurer, MD | Credit: Charite Berlin

Marcus Maurer, MD
Credit: Charite Berlin

Phase 2 data from a trial presented at the 2024 American Academy of Allergy, Asthma and Immunology (AAAAI) Annual Meeting suggest the oral BTK inhibitor rilzabrutinib was effective in reducing itch relief and disease activity among adults with chronic spontaneous urticaria (CSU) in as little as 1 week.

According to a release from Sanofi, results of the phase 2 RILECSU indicate use of rilzabrutinib significantly improved itch, hives and urticaria in adults with moderate-to-severe CSU and inadequate symptoms control with H1 antihistamines. The company noted data from the trial are the basis of phase 3 programs in CSU and prurigo nodularis, which are slated to begin later this year.1,2

“People with CSU are living with debilitating symptoms such as intensely itchy recurrent hives, swelling, or both which can have a high impact on their day-to-day lives. These data are promising news for patients that cannot be controlled with standard-of-care antihistamines – the possibility of controlling itch rapidly with an oral medicine would offer an important advancement in the treatment of this disease,” said principal investigator Marcus Maurer, MD, professor of Dermatology and Allergy and executive director of the Institute of Allergology at the Charité Berlin.2

An oral, reversible, covalent BTK inhibitor, rilzabrutinib is billed by Sanofi as having the potential to be a first- or best-in-class treatment of a number of immune-mediated diseases. According to the aforementioned release, it is 1 of 12 agents currently in development within Sanofi’s immunology pipeline.2

Phase 2 RILECSU Background

A phase 2 dose-ranging trial, RILECSU was designed as a parallel, 12-week, double-blind, 4-arm study with the aim of assessing the safety and effectiveness of 3 oral doses of rilzabrutinib relative to placebo therapy. A total of 160 were randomized in a 1:1:1:1 ratio to placebo, 400 mg rilzabrutinib once every evening, 400 mg twice a day, or 400 mg 3 times a day.1

For inclusion in the trial, patients needed to have a diagnosis of CSU refractory to H1-AH at the time of randomization, be diagnosed at least 3 months before first screening visit, and presence of itch and hives for 6 or more consecutive weeks at any time prior to screening despite use of H1-AH during this period.1

The primary outcome of interest for the trial was change from baseline in weekly itch severity score (ISS7) at 12 weeks. Secondary outcomes of interest included change from baseline in weekly urticaria activity score (UAS7) at 12 weeks and change from baseline weekly hives severity score (HSS7) at 12 weeks.1

Of note, following the conclusion of the double-blind portion of the study participants are offered the option of enrolling in the 40-week, open-label extension phase of the trial.2

Reduced Itch Severity and Disease Activity

Upon analysis of the trial’s intent-to-treat population, use of 400 mg rilzabrutinib 3 times daily was associated with a statistically significant reduction in ISS7 at week 12 (least squares mean [LSM] -9.58 vs -6.31, respectively; P=.0181), with investigators highlighting significant changes seen as early as week 1. Analysis of secondary outcomes of interest suggested those receiving400 mg rilzabrutinib 3 times daily was associated with significant reductions from baseline to week 12 in UAS7 (LSM -17.95 vs -11.20, respectively; P=.0116) and HSS7 (LSM -8.31 vs -4.89; P <.0100).1

Rilzabrutinib’s Safety Profile

Analysis of safety events during the trial indicated rilzabrutinib was generally well-tolerated with no events of cytopenia, bleeding or atrial fibrillation seen with other BTK inhibitors. A summary of the treatment-emergent adverse events occurring at a greater frequency than placebo therapy is highlighted below:1,2


Rilzabrutinib 400 mg Every Evening

Rilzabrutinib 400 mg Twice Daily

Rilzabrutinib 400 mg 3 Times Daily
















Abdominal Pain






  1. Maurer M, Gimenez-Arnau A, Ferrucci S, et al. Efficacy and Safety of Rilzabrutinib in Patients With Chronic Spontaneous Urticaria: 12-Week Results From the RILECSU Phase 2 Dose-Ranging Study. Paper presented at: 2024 American Academy of Allergy, Asthma and Immunology (AAAAI) Annual Meeting; February 23 - 26; Washington DC. Accessed February 24, 2024.
  2. Sanofi. Press release: Phase 2 results demonstrate rilzabrutinib rapidly reduced itch severity and significantly improved disease activity in adults with chronic spontaneous urticaria. Sanofi Media Room. February 24, 2024. Accessed February 24, 2024.

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