Celldex says barzolvolimab study meets primary endpoint, will not advance in EoE

Celldex (CLDX) reported topline results from the company’s ongoing Phase 2 study of barzolvolimab in eosinophilic esophagitis, a chronic inflammatory disease of the esophagus. The primary endpoint of the study, absolute change from baseline to Week 12 in peak esophageal intraepithelial mast cell count was met, but the profound mast cell depletion observed did not result in improvement in EoE symptoms or endoscopic assessment of disease activity compared to placebo. Consistent with previously reported studies, barzolvolimab demonstrated a favorable safety and tolerability profile. Based on these results, Celldex will not advance development in EoE. The results do support future development with KIT- or SCF-targeted therapies in other GI indications where mucosal mast cells are believed to play an important role. Profound reduction in CD117+ and tryptase+ intraepithelial mast cells. Primary endpoint met with high statistical significance. Peak mast cell counts per high power field at baseline were 50.3 in the placebo arm and 55.4 in the barzolvolimab 300mg Q4W arm. At Week 12 the absolute change from baseline was -2.7 for placebo compared to -36.0 for barzolvolimab. Mast cells defined by tryptase staining also showed profound decreases at week 12 in barzolvolimab treated patients with sustained and deepening decreases observed at Week 28. Despite profound mast cell depletion, no definitive evidence of clinical improvement in EoE symptoms, as measured by the Dysphagia Symptom Questionnaire, or endoscopic scoring of EoE-related inflammation & fibrosis were observed compared to placebo. There was also no difference observed in histological reduction in esophageal intraepithelial infiltration of eosinophils. Barzolvolimab demonstrated a favorable safety profile at the 300 mg Q4 weekly dosing regimen, consistent with prior studies where barzolvolimab was dosed less frequently. An unblinded review of all available data through the full treatment period and full study was conducted and clinical and safety outcomes were consistent at these timepoints.