Cue Biopharma: CUE-221 beats placebo and omalizumab in CSU trial

Cue Biopharma has reported positive topline results from a Phase 2 trial of CUE-221 in moderate-to-severe chronic spontaneous urticaria (CSU), saying the anti-IgE monoclonal antibody met its primary and key secondary endpoints with high statistical significance and demonstrated a durable response that persisted well beyond the end of the dosing period.

The multicentre, randomised, double-blind study, conducted in China by Genesis Life Sciences, enrolled 145 participants whose disease remained inadequately controlled on H1 antihistamines. Patients were randomised across five arms: CUE-221 at 4 mg/kg, 2 mg/kg or 1 mg/kg every four weeks; matching placebo; or omalizumab (Xolair) 300 mg every four weeks. Omalizumab was included as a comparator to contextualise efficacy, though no head-to-head statistical test was pre-specified.

Trial results

At week 12, the primary endpoint of complete hive resolution (HSS7=0) was achieved by 54%, 53% and 43% of patients in the 4 mg/kg, 2 mg/kg and 1 mg/kg CUE-221 arms, respectively, compared with 11% on placebo and 41% on omalizumab. All three CUE-221 doses achieved statistical significance versus placebo. The key secondary endpoint, complete response by UAS7=0, was met at the 4 mg/kg dose level (46% versus 11% on placebo).

The durability data are striking. Efficacy continued to increase after week 12, peaking at week 22 across all CUE-221 dose groups. Twelve weeks after the last dose, the 4 mg/kg group maintained a 60% hive resolution rate, versus 24% for omalizumab at the same timepoint, a post hoc difference of 36 percentage points that reached statistical significance. The company says this pattern is consistent with a mechanistic difference: CUE-221 is designed to allow IgE to bind to CD23 receptors on B cells, suppressing new IgE synthesis over time, a feature that distinguishes it from omalizumab's simpler neutralisation approach.

The safety profile was clean. There were no treatment-related serious adverse events, no hypersensitivity reactions or anaphylaxis, and injection site reactions were infrequent, with only one graded above Grade 1.

Market and competitive context

CSU is a sizeable indication. Omalizumab, marketed by Novartis and Genentech as Xolair, has been the established standard of care for antihistamine-refractory CSU since its approval in that indication in 2014, and it also holds approval for food allergy. The market has attracted additional entrants: dupilumab, approved in several countries for CSU, and a number of other biologics in varying stages of development targeting the type 2 inflammatory pathway. Against this backdrop, a candidate that matches or exceeds omalizumab on an absolute response rate and then sustains that response after stopping treatment would represent a genuinely different clinical proposition.

Cue plans to initiate a Phase 2b/3 trial in CSU and a separate Phase 2 study in food allergy, where omalizumab also holds reference-standard status. The company has not disclosed timelines for either study, nor has it announced any commercial partnership for ex-China territories, where it holds exclusive rights under licence from Ascendant Health. Full data, including pharmacokinetic and IgE analyses from the 36-week study, are expected at an upcoming scientific meeting.

One caveat for investors: the Phase 2 data come from a trial conducted entirely in China, and the FDA may require additional evidence to satisfy its standards for bridging to a global population, a consideration the company will need to address as it designs the Phase 2b/3 programme.