Celldex Therapeutics (Nasdaq: CLDX) reported positive Phase III results for barzolvolimab in chronic spontaneous urticaria (CSU), with both pivotal EMBARQ studies meeting their primary and all key secondary endpoints. The readout gives the KIT-targeting antibody a major boost after a Phase II failure in prurigo nodularis in July and an earlier discontinuation in eosinophilic esophagitis, and positions Celldex for a planned 2027 FDA filing.
Barzolvolimab is a humanized monoclonal antibody that binds the KIT receptor on mast cells, blocking stem cell factor signaling and depleting the cells that drive CSU pathology. The mechanism acts upstream of the IgE pathway targeted by Genentech and Novartis's Xolair (omalizumab) and downstream of the IL-4/IL-13 axis targeted by Sanofi and Regeneron's Dupixent (dupilumab), and differs from the intracellular BTK inhibition used by Novartis's Rhapsido (remibrutinib), the first oral targeted therapy approved for CSU, which received FDA approval in September 2025 and EU approval in April 2026.
The two global Phase 3 studies — EMBARQ-CSU1 and EMBARQ-CSU2 — randomized 1,939 patients with antihistamine-refractory CSU, including omalizumab-refractory patients, across 43 countries and more than 500 sites. Patients received barzolvolimab 150 mg every four weeks (following a 300 mg loading dose), 300 mg every eight weeks (following a 450 mg loading dose), or placebo for 24 weeks, with active treatment continuing to 52 weeks.
Both doses produced highly statistically significant reductions in the weekly urticaria activity score (UAS7) at Week 12 versus placebo in both studies (p<0.00001 for all comparisons). In EMBARQ-CSU1, the 150 mg and 300 mg arms produced least-squares mean changes from baseline of −20.2 and −20.5 respectively, compared with −10.7 for placebo. Results in EMBARQ-CSU2 were consistent: −20.2 and −19.7 versus −11.4. Complete response rates (UAS7=0) at Week 12 ranged from 42.1% to 45.7% across both doses and studies, versus 9.3% to 12.6% for placebo, and deepened to 45.1%–54.0% by Week 24. In the omalizumab-refractory subpopulation, complete response rates at Week 12 reached 41.7%–55.3% with barzolvolimab versus 9.3%–15.1% with placebo. Among patients with angioedema at baseline, 62.7%–74.3% achieved complete angioedema resolution (AAS7=0) at Week 12 versus 33.7%–33.8% with placebo. Celldex said the safety profile through the 24-week placebo-controlled period was consistent with prior Phase II experience. Specific adverse event rates were not disclosed in the topline release.