Celldex’s barzolvolimab restores efficacy in cold urticaria, dermographism in Phase II

Celldex Therapeutics reported Phase II open-label extension data showing that retreatment with barzolvolimab restores efficacy in patients with cold urticaria (ColdU) and symptomatic dermographism (SD), producing response rates comparable to those seen during initial treatment. The findings were presented in a late-breaking poster at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2026 meeting and suggest that barzolvolimab could potentially be used in an intermittent dosing strategy if approved.

Barzolvolimab is a monoclonal antibody targeting the KIT receptor (c-KIT/CD117), a central regulator of mast cell survival and activation. The drug is currently the only anti-KIT antibody in registrational development for chronic inducible urticarias, conditions that lack approved targeted therapies beyond antihistamines, following announcement of Phase III initiation in December 2025.

Trial specifics

The Phase II trial enrolled 193 adults — 96 with ColdU and 97 with SD — randomized to receive barzolvolimab 150 mg every four weeks, barzolvolimab 300 mg every eight weeks, or placebo during a 20-week double-blind period.

Patients whose symptoms returned during follow-up were eligible to enter the open-label extension (OLE). Of the 121 patients who enrolled in the extension (61 ColdU and 60 SD), 116 completed retreatment. Median time to re-entry into the OLE was 56 days for patients initially assigned to placebo and 105 days for those originally treated with barzolvolimab, reflecting the drug’s sustained pharmacodynamic effect.

During retreatment, 62% of ColdU patients and 60% of SD patients achieved complete response at Week 20. These results closely mirrored the complete response rates observed during the initial trial period (66% for ColdU and 49% for SD).

Among patients who had achieved a complete response during the main study, retreatment results were stronger: 82% of ColdU patients and 86% of SD patients regained complete response, while 95% and 100%, respectively, achieved at least partial response. Urticaria control rates reached 68% in ColdU and 69% in SD. Celldex said the safety profile during retreatment was consistent with prior studies and that the therapy remained well tolerated, though detailed adverse event rates were not disclosed.

Research context

Barzolvolimab targets the KIT receptor, a tyrosine kinase that regulates mast cell development and activity. By blocking KIT signaling, the drug reduces mast cell numbers and suppresses activation, addressing the underlying mechanism of inducible urticarias rather than targeting downstream mediators such as histamine.

ColdU and SD are mast-cell-driven conditions in which triggers such as cold exposure or mechanical friction provoke rapid mast cell degranulation, producing wheals, itching, and swelling. Current treatment relies primarily on H1-antihistamines, often at increased doses, but many patients remain symptomatic.

Celldex has already launched the Phase III EMBARQ program evaluating barzolvolimab in adults with ColdU or SD inadequately controlled by antihistamines. If the registrational trials confirm the Phase II results, barzolvolimab could become the first targeted therapy approved for these forms of inducible urticaria.