Celldex Therapeutics has discontinued development of barzolvolimab for prurigo nodularis (PN) after the treatment failed to meet the primary and key secondary endpoints in a phase 2 study.
Barzolvolimab is an anti-KIT antibody designed to deplete mast cells, which are involved in allergic reactions and inflammation. Celldex has been developing the drug for several inflammatory conditions. The company selected chronic spontaneous urticaria (CSU) and cold urticaria, a form of chronic inducible urticaria (CIndU), as its lead indications and is conducting phase 3 trials in those settings. It has also been evaluating the therapy in atopic dermatitis (AD) and prurigo nodularis through mid-stage studies.
The phase 2 PN trial enrolled patients with the chronic skin disease, which causes intensely itchy skin lumps and nodules. The study failed to achieve its primary endpoint, which measured improvement on an itch scale at Week 12. Barzolvolimab also did not demonstrate meaningful improvement in key secondary measures, including symptoms and skin lesions, compared with placebo.
The outcome occurred despite what Celldex described as profound systemic mast cell depletion. The company had advanced into phase 2 testing after a phase 1b study linked barzolvolimab to improvements in itch compared with placebo. For the phase 2 study, Celldex changed the administration method from intravenous delivery to subcutaneous injection.
TD Cowen analysts said the change in administration route may have contributed to the inability to reproduce the earlier results. However, they suggested that “the more likely conclusion is that mast cells are simply not a pathogenic driver for PN.”
Celldex also noted that while barzolvolimab sharply reduced mast cells, patients did not experience an improvement in symptoms. The company said this suggests mast cells may not be a major driver of prurigo nodularis.
The findings have implications for the ongoing phase 2 trial in atopic dermatitis, with results expected later this year. TD Cowen analysts said the PN outcome weakens the argument for barzolvolimab in AD because both diseases include pruritic components that had been hypothesized to be mast-cell driven.
During a conference call with investors, Chief Scientific Officer Tibor Keler said that overlap between the indications was part of the rationale for conducting the AD study after seeing phase 1b data in PN. He also said mast cells affect other aspects of the inflammatory process in AD, and the company plans to complete the trial.
Celldex reported that barzolvolimab showed a favorable safety and tolerability profile in the PN study and that the overall safety findings were consistent with prior studies. An investigator reported a case of aseptic meningitis as a serious treatment-related adverse event, but Celldex disagreed with both the diagnosis and its relationship to the drug. Chief Medical Officer Diane Young said, “We have no concerns about efficacy.”
The company said it remains focused on developing barzolvolimab for other inflammatory and allergic conditions. Late-stage trial data in CSU are expected in September or October 2026, while mid-stage data in atopic dermatitis are due later in the year. Following disclosure of the PN results, Celldex shares fell more than 7% in extended and premarket trading.
Celldex has announced the discontinuation of barzolvolimab development for prurigo nodularis (PN) after the investigational therapy failed to achieve its primary and secondary endpoints in a Phase 2 clinical trial. The decision reflects the company’s commitment to prioritizing resources toward programs with stronger clinical potential while maintaining a disciplined research and development strategy.
Celldex Discontinues Barzolvolimab Program in Prurigo Nodularis
The Phase 2 study evaluated barzolvolimab as a potential treatment for patients with prurigo nodularis, a chronic inflammatory skin condition characterized by severe itching and skin lesions. According to Celldex, the trial did not demonstrate sufficient clinical benefit to support continued development for this indication. Based on these findings, the company has decided to end the program for PN.
