A midstage study of Cue Biopharma’s hives drug candidate has hit its primary endpoint, emboldening the biotech to move the would-be challenger to Xolair into a phase 2b/3 trial.
In April, Cue paid Ascendant Health Sciences $15 million for ex-China rights to the asset, CUE-221. At that time, Ascendant’s Genesis Life Sciences was nearing the end of a phase 2 study of CUE-221 in chronic spontaneous urticaria (CSU), a skin condition that causes hives. The trial was placebo controlled but dosed a cohort with Xolair, a CSU drug sold by Novartis and Roche, to enable comparative efficacy.
The 145 subjects enrolled in China received one of three doses of CUE-221 or placebo subcutaneously every four weeks. At Week 12, hives were completely resolved in 43% to 54% of people in the CUE-221 cohorts, based on the HSS7 scale, compared to 11% of their peers on placebo.
All the CUE-221 resolution rates were statistically significant versus placebo, achieving the trial’s primary endpoint. The CUE-221 cohorts performed numerically better than the Xolair arm, which reported a 41% resolution rate. Genesis used the Xolair group to enable comparative efficacy without planned statistical testing.
A secondary endpoint revealed a similar pattern. Between 38% and 46% of patients receiving CUE-221 had a complete response on the UAS7 scale. The complete response rates on placebo and Xolair were 11% and 29%, respectively.
Cue reported deepening responses after Week 12. Investigators administered a final dose at Week 16 and tracked patients through Week 28. CUE-221’s effect peaked at Week 22, when the HSS7 resolution rate was up to 69% on the study drug and 41% on Xolair.
The gap between the treatments widened by Week 28. By then, the response rate on the high dose of CUE-221 was 60%, compared to 24% on Xolair. The high dose of CUE-221 was an outlier at Week 28—the response rates for the two lower doses were 31% and 24%.
Cue hailed the Week 28 gap between the CUE-221 and Xolair response rates as evidence that its asset has a fundamentally different impact on disease biology. Like Xolair, Cue’s drug is designed to neutralize free IgE. But CUE-221 is engineered to go a step further, downregulating IgE production to drive deeper, more durable disease control.
Boosted by clinical data supporting that hypothesis, Cue plans to start a phase 2b/3 study in CSU. The biotech will work toward the trial while continuing to gear up for a phase 2 food allergy study. Cue raised $50 million in July, enabling the company to tell investors in August that it had enough cash for at least the next 12 months.