CUE-221 (UB-221), a dual-mechanism anti-IgE monoclonal antibody being developed by Boston-based Cue Biopharma (Nasdaq: CUE), met both its primary and key secondary endpoints in a Phase II study in chronic spontaneous urticaria (CSU), according to topline results released September 20. The data, generated in China by Genesis Life Sciences under an arrangement with Cue's China-based licensor Ascendant Health Limited, support progression to a Phase IIb/III registration-enabling study.
The randomized, double-blind, placebo- and active comparator-controlled trial enrolled 145 adults with moderate to severe CSU inadequately controlled despite H1 antihistamines. Patients received subcutaneous CUE-221 at 4 mg/kg, 2 mg/kg, or 1 mg/kg every four weeks (Q4W), placebo Q4W, or Novartis's Xolair (omalizumab) 300 mg Q4W. The primary endpoint — proportion of patients achieving a hive severity score of zero (HSS7=0) at week 12 — was met at all three dose levels, with rates of 54%, 53%, and 43% respectively versus 11% for placebo (p<0.005, p<0.005, p<0.05). The key secondary endpoint, complete response defined as UAS7=0 at week 12, reached statistical significance at the 4 mg/kg dose (46% versus 11% for placebo, p<0.05). Omalizumab achieved HSS7=0 in 41% of patients at week 12; statistical comparison against CUE-221 was not pre-specified.
CUE-221 (also known as UB-221) binds free IgE at epitopes distinct from those targeted by omalizumab, blocking its interaction with the high-affinity IgE receptor (FcεRI) on mast cells and basophils while preserving IgE's ability to engage the CD23 receptor on B cells — a mechanism the company says suppresses new IgE synthesis over time.
At week 22 — six weeks after the final dose — the 4 mg/kg group reached a peak HSS7=0 rate of 69%, compared with 41% for omalizumab. At week 28, twelve weeks after the last dose, 60% of patients in the 4 mg/kg arm maintained complete resolution of hives versus 24% in the omalizumab arm; a post hoc analysis reported this difference as statistically significant (delta = 36%, p<0.05). The post hoc nature of the week-28 comparison limits its evidentiary weight, and the omalizumab arm was not powered for statistical testing. Complete PK and IgE analyses from the 36-week study have not yet been disclosed.
CUE-221 demonstrated a favorable safety profile with no treatment-related serious adverse events and no hypersensitivity reactions including anaphylaxis. Injection site reactions were infrequent, with only one exceeding grade 1.