Celldex Advances Barzolvolimab into Phase 3 Trials for Cold Urticaria and Symptomatic Dermographism
核心洞察
Celldex Therapeutics has initiated EMBARQ-ColdU and SD, a global phase 3 program evaluating barzolvolimab in adults with cold urticaria (搜索) and symptomatic dermographism (搜索) who remain symptomatic despite antihistamine therapy.
The randomized, double-blind, placebo-controlled trial will enroll approximately 240 patients across 75 sites in seven countries, with the primary endpoint measuring complete response rates at week 12.
Previous phase 2 results showed up to 75% of cold urticaria (搜索) patients and 67% of symptomatic dermographism (搜索) patients achieved partial or complete response by week 12, with no advanced therapies currently approved for these conditions affecting over 533,000 patients in the US and Europe.
Celldex Therapeutics has launched its second phase 3 program for barzolvolimab, initiating the global EMBARQ-ColdU and SD trial to evaluate the KIT (搜索)-targeting monoclonal antibody in adults with cold urticaria (搜索) (ColdU) and symptomatic dermographism (搜索) (SD) who remain symptomatic despite guideline-based antihistamine therapy. The advancement represents a significant milestone for patients with these debilitating conditions, for which no advanced therapies are currently approved.
"Across studies in cold urticaria (搜索) and symptomatic dermographism (搜索), barzolvolimab has demonstrated a unique and profound ability to offer rapid, sustained, complete disease response, providing hope for patients who are impacted by severe itching and hives that dramatically impact all aspects of their lives despite constant vigilance to avoid disease triggers," said Diane C. Young, MD, Senior Vice President and Chief Medical Officer of Celldex.
Phase 3 Trial Design and Endpoints
The EMBARQ-ColdU and SD phase 3 trial is designed as a randomized, double-blind, placebo-controlled, parallel-group study enrolling approximately 240 adults across approximately 75 sites in seven countries. Participants will be categorized into two cohorts by disease subtype, with approximately 120 patients planned for each condition. The study includes patients with inadequate response to H1 antihistamines (搜索), and those previously treated with biologics are also eligible for enrollment.
Participants will be randomized 1:1 to receive either barzolvolimab or placebo. The active-treatment regimen consists of a 450 mg loading dose on day 1, followed by 150 mg every 4 weeks for 24 weeks. The primary endpoint measures the proportion of patients achieving a complete response, defined as a negative provocation test at week 12 using the TempTest for ColdU and FricTest for SD. Secondary outcomes will examine symptomatic and functional improvements, with patients followed for an additional 16 weeks after completing treatment.
Compelling Phase 2 Results Drive Advancement
The phase 3 initiation follows compelling signals from a prior placebo-controlled phase 2 study, in which barzolvolimab met all primary and secondary endpoints with high statistical significance. In that study, up to 75% of patients with ColdU and 67% with SD achieved partial or complete response by week 12. The improvements included enhanced Critical Temperature Thresholds (CTT), Critical Friction Thresholds (CFT), itch reduction per WI-NRSprovo, and better Urticaria Control Test scores.
Importantly, responses were durable and strengthened over time. By week 20, up to 78% of ColdU and 58% of SD patients maintained partial or complete response. The safety profile in phase 2 was favorable, with follow-up extending 24 weeks beyond treatment. Patients with persistent or returning symptoms were eligible for an open-label extension, with placebo-treated patients entering the extension sooner than those treated with barzolvolimab. Data from the open-label extension are expected in Q1 2026.
Addressing Significant Unmet Medical Need
There are currently no advanced therapies approved to treat the more than 533,000 patients impacted by ColdU and SD across the United States and Europe. Patients are typically treated with up to four times the labeled dose of antihistamines (搜索), but more than 80% continue to report inadequate disease control.
ColdU and SD are characterized as diseases of misery, with patients often finding it impossible to avoid disease triggers despite best efforts. They are impacted by severe itching and burning hives that dramatically affect all aspects of their lives. More than 60% of patients report moderate to severe impact on their mental/emotional well-being, daily activities, and social/intimate relationships, suffering from social stigma, including being asked if they are contagious, being stared at in public, and people refusing to shake hands or touch them. Patients with ColdU and SD also report high rates of anxiety and depression.
Mechanism of Action and Broader Development Program
Barzolvolimab is a humanized monoclonal antibody targeting the receptor tyrosine kinase KIT (搜索), a central regulator of mast-cell differentiation, recruitment, and survival. Given that mast-cell activation is the primary driver of both ColdU and SD, the drug is designed to address disease pathophysiology upstream of symptom-mediator release.
"Barzolvolimab is now advancing across five indications demonstrating its significant potential to treat a broad array of mast cell driven diseases with Phase 3 studies ongoing in chronic spontaneous urticaria (搜索), cold urticaria (搜索) and symptomatic dermographism (搜索) and Phase 2 studies in prurigo nodularis (搜索) and atopic dermatitis (搜索)," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex. "We remain focused on executing these trials seamlessly and achieving our goal of making barzolvolimab available to meet the needs of patients."
At the 2025 European Academy of Dermatology and Venereology (EADV) Congress in Paris, France, Celldex presented data on the use of barzolvolimab in patients with chronic spontaneous urticaria (搜索) (CSU). Participants demonstrated rapid and sustained efficacy via weekly Urticaria Activity Scores, regardless of baseline immunoglobulin E (IgE) levels. The drug was also well-tolerated with a favorable safety profile across treatment durations.