HAMPTON, N.J., July 21, 2026
Celldex announced topline results from its Phase 2 clinical trial evaluating barzolvolimab in patients with prurigo nodularis (PN), a chronic inflammatory skin disease characterized by intensely itchy nodules. While the investigational monoclonal antibody demonstrated a favorable safety and tolerability profile, the study did not achieve its primary endpoint or key secondary efficacy objectives. As a result, the company has decided to discontinue the Phase 2 PN program. Despite the disappointing efficacy outcome, the trial confirmed rapid and profound systemic mast cell depletion, evidenced by a significant reduction in serum tryptase, reinforcing barzolvolimab’s biological activity. Celldex emphasized that its broader clinical development strategy remains intact, with multiple Phase 3 and Phase 2 programs continuing across other mast cell-driven diseases.
Phase 2 Study Misses Primary Efficacy Endpoints
The randomized, double-blind, placebo-controlled Phase 2 study enrolled 140 patients with moderate-to-severe prurigo nodularis who had an inadequate response to topical therapies or for whom topical treatment was not appropriate. Participants received barzolvolimab 150 mg or 300 mg every four weeks following a 450 mg loading dose, or placebo, over a 24-week treatment period. The primary endpoint measured the proportion of patients achieving at least a 4-point improvement in the Worst Itch Numeric Rating Scale (WI-NRS) at Week 12. The study also evaluated improvements in skin lesions using the Investigator’s Global Assessment for Chronic Nodular Prurigo (IGA-CPNG-S). According to Celldex, neither dosing regimen demonstrated statistically meaningful improvement over placebo, and no additional clinical benefit emerged after 24 weeks of treatment, indicating that mast cell depletion alone may not sufficiently address the underlying disease mechanisms in PN.
Strong Safety Profile Supports Ongoing Mast Cell Research
Although efficacy objectives were not achieved, barzolvolimab maintained a favorable safety profile, consistent with previous studies conducted across multiple inflammatory diseases. Investigators observed rapid, sustained suppression of circulating serum tryptase, confirming extensive mast cell depletion throughout the treatment period. The inclusion of the new 450 mg loading dose enabled earlier and deeper reductions in mast cell activity, validating the drug’s intended biological mechanism. Celldex noted that these findings suggest mast cells may not be the primary pathogenic driver of prurigo nodularis symptoms, despite being successfully targeted by the therapy. Company leadership highlighted that these results contribute valuable scientific insights into mast cell biology and will help refine future therapeutic strategies targeting allergic, inflammatory, and autoimmune diseases.
Advertisement
Phase 3 Programs Continue Across Multiple Indications
Despite discontinuing the PN program, Celldex remains focused on advancing barzolvolimab in diseases where previous studies have demonstrated compelling efficacy. The company reported that Phase 3 clinical trials in chronic spontaneous urticaria (CSU), symptomatic dermographism (SD), and cold urticaria (ColdU) remain on schedule, with topline Phase 3 CSU data expected during September or October 2026. In addition, a Phase 2 trial in atopic dermatitis (AD) is expected to report topline results later this year. Company executives reaffirmed their commitment to establishing barzolvolimab as a first-in-class mast cell-targeting therapy, leveraging its differentiated mechanism of action and strong safety profile while continuing to evaluate its potential across multiple allergic, inflammatory, and autoimmune disorders.
Source: Celldex,press release
