Celldex touted a double phase 3 trial win in patients with treatment-refractory chronic spontaneous urticaria (CSU).
The trials met both primary and secondary endpoints, giving Celldex’s barzolvolimab a chance at redemption after its recent phase 2 flop in a different chronic skin condition.
Barzolvolimab is a monoclonal antibody that binds to the receptor tyrosine kinase KIT and inhibits its activity. KIT is expressed in mast cells, the primary drivers of the inflammatory response in CSU. The abnormal activation of these cells leads to the itchy hives and swelling seen in the condition.
The trials will continue for 52 weeks, with Celldex planning to submit for FDA approval in 2027, according to the release.
“We believe barzolvolimab is well-positioned to address large CSU populations of high unmet need,” Anthony Marucci, Celldex co-founder, president and CEO, said in the release. “We look forward to continuing to grow our leadership in mast cell biology as we advance to our next stage of development—establishing a commercial-stage organization committed to delivering barzolvolimab to patients and physicians in need as quickly as possible.”
The Embarq CSU1 and CSU2 trials enrolled a total of 1,939 patients in randomized, double-blind, placebo-controlled global studies. Patients received 150 mg of subcutaneous barzolvolimab every four weeks following a 300-mg loading dose, 300 mg every eight weeks following a 450-mg loading dose for 52 weeks or placebo for 24 weeks.
Patients who received either dose of barzolvolimab showed significant improvement in daily itch and hive scores, measured by the weekly urticaria activity score (UAS7), at week 12. Additionally, significantly more patients achieved a complete response with either the 150-mg or 300-mg dose of barzolvolimab at 12 and 24 weeks compared with placebo.
The studies also enrolled patients with CSU that was resistant to treatment with Genentech and Novartis’ Xolair (omalizumab). In this subpopulation of patients treated with the 150-mg dose of barzolvolimab, 55.3% and 41.7% achieved a complete response compared with 9.3% and 15.1% in the placebo-treated groups at week 12. In those treated with the 300-mg dose, 44.3% and 46.4% achieved a complete response by week 12. Only two patients experienced anaphylaxis following administration, with an overall 16% discontinuation rate, mainly due to patients withdrawing consent, the company noted during its Sept. 22 conference call.
In July 2026, Celldex reported the failure of the phase 2 prurigo nodularis trial after it missed its primary endpoint, which looked for improvements on an itch scale at week 12. Barzolvolimab also failed to move the needle on secondary endpoints, despite Celldex reporting at the time “profound systemic mast cell depletion.”
Just yesterday, Cue Biopharma announced that its drug candidate, CUE-221, hit its primary endpoint in a phase 2 CSU trial, emboldening the biotech to move into a phase 2b/3 trial. Cue’s drug is designed to neutralize free IgE before it triggers inflammatory cells, similar to Xolair. CUE-221 is also engineered to preserve signaling through CD23, a receptor involved in regulating IgE production, with the aim of reducing the production of new IgE.