D2.495 - Treatment with Izicopan (INF904), an oral anti-C5aR inhibitor improves efficacy and safety in patients with chronic spontaneous urticaria: results from a Phase 2a study

The activation and recruitment of neutrophils to the skin with release of mediators such as C5a, a potent anaphylatoxin, are being recognised to play a critical role in the inflammatory response in CSU.  C5a can further amplify the release of histamine whilst its release can also be perpetuated by the coagulation cascade via the localised vascular endothelium. Izicopan is a potentially best-in-class oral anti-C5aR1 inhibitor. This Phase 2a study evaluated the safety, pharmacokinetics and efficacy of Izicopan in patients with moderate to severe CSU; here we report on the clinical efficacy to date

This Phase 2a, open-label study enrolled adults with moderate to severe CSU. Patients were randomised to receive izicopan 60 mg twice daily or 120 mg (BID) for 4 weeks. In addition, a third  cohort included patients previously treated with anti-IgE therapy and or with low total IgE levels (<40 IU/mL). Patients were assessed weekly during treatment and followed for 4 weeks after treatment discontinuation.

A total of 38 patients were enrolled with mean baseline UAS7 score ranging from 30.4 to 31.4 (SD 7.2) across the treatment groups. The mean change (SD) in UAS7 from baseline at week 4 for izicopan 60mg BID and 120mg BID were -13.6 (8.7) and -9.5 (12.0), respectively. Deepening of UAS7 response to -15.6 (6.4) and -9.8 (13.4) was observed at the end of study after four weeks of discontinued treatment. A subset of patients (n=8) who had previously responded to and/or those who were refractory to anti-IgE therapy, showed improvement of UAS7 (mean CFB) -12.4. Patients UCT7 also improved by 4.9 points in both groups. Safety adverse events were mild to moderate, with no serious AE reported.

Treatment with izicopan for 4 weeks was associated with clinically meaningful improvements in disease activity and control in moderate to severe CSU patients, including sustained effects after treatment discontinuation. Izicopan demonstrated a favourable safety and tolerability profile, supporting further clinical development in CSU.