Celldex Therapeutics (Hampton, New Jersey; Nasdaq: CLDX) reported topline results from a Phase II study of subcutaneous barzolvolimab in prurigo nodularis, revealing the trial failed to meet its primary or key secondary endpoints. This is the second efficacy setback for the anti-KIT antibody, following a failed Phase II study in eosinophilic esophagitis, where pharmacodynamic evidence of mast-cell depletion did not translate into clinical benefit. It represents the first efficacy failure for barzolvolimab in a dermatologic disease, having previously demonstrated proof-of-concept activity across three mast cell-mediated dermatologic indications—chronic spontaneous urticaria, cold urticaria and symptomatic dermographism.
In the randomized, double-blind, placebo-controlled trial (NCT06366750), 140 patients received barzolvolimab 150mg or 300mg every four weeks following a 450mg loading dose, or placebo, over a 24-week treatment phase. The proportion of patients achieving a four-point or greater improvement in the Worst Itch Numeric Rating Scale at Week 12 did not differentiate from placebo at either dose, nor did the proportion reaching an Investigator's Global Assessment score of 0/1. No separation from placebo emerged through Week 24. Celldex said serum tryptase, a marker of mast cell burden, fell rapidly and was sustained throughout treatment, indicating profound systemic mast cell depletion that nonetheless did not translate into clinical benefit. The company described barzolvolimab as well tolerated, with a safety profile consistent with prior studies, though it did not report specific adverse event rates.
The study enrolled adults with moderate to severe prurigo nodularis who had an inadequate response to topical therapy, across 48 centers in six countries. The results are topline, while a 16-week off-treatment follow-up and optional open-label extension remain ongoing. Efficacy data from the core treatment phase were conclusive enough that Celldex is discontinuing the PN program.