Celldex's Barzolvolimab Hits Primary Endpoint in Both Phase 3 CSU Trials
核心洞察
Celldex reported positive topline results from the Phase 3 EMBARQ-CSU1 and EMBARQ-CSU2 trials of barzolvolimab in antihistamine-refractory chronic spontaneous urticaria (搜索).
Both trials met the primary endpoint of mean change from baseline in weekly urticaria activity score (UAS7) at Week 12 across both dose groups with p<.00001 versus placebo.
Complete response rates (UAS7=0) reached roughly 42% to 46% at Week 12 and 45% to 54% at Week 24, versus 9% to 18% for placebo.
Celldex Therapeutics reported positive topline results from its Phase 3 EMBARQ-CSU1 and EMBARQ-CSU2 trials of barzolvolimab in patients with chronic spontaneous urticaria (搜索) (CSU) whose symptoms are inadequately controlled by H1-antihistamines. Both trials met the primary endpoint of mean change from baseline in weekly urticaria activity score (UAS7) at Week 12, along with all key secondary endpoints, across both dose groups. The data cutoff was September 9, 2026.
The company described the EMBARQ-CSU program as the largest conducted in antihistamine-refractory CSU, including patients with advanced therapy experience or refractory disease.
Primary Endpoint Results
Baseline UAS7 scores were approximately 30 in both studies. In EMBARQ-CSU1, the least-squares (LS) mean change at Week 12 was -10.7 (SE 0.65) for placebo, -20.2 (SE 0.64) for barzolvolimab 150 mg every 4 weeks and -20.5 (SE 0.65) for 300 mg every 8 weeks, with p<.00001 for both active arms versus placebo.
In EMBARQ-CSU2, the LS mean change at Week 12 was -11.4 (SE 0.64) for placebo, -20.2 (SE 0.63) for the 150 mg dose and -19.7 (SE 0.64) for the 300 mg dose, also with p<.00001 for both comparisons. P-values were for the LS mean treatment difference versus placebo.
Celldex reported that efficacy was sustained or deepened from Weeks 12 to 24 across the primary and all key secondary endpoints.
Complete Response Rates
The company presented UAS7=0 data, defined as complete absence of itch and hives, at both 12 and 24 weeks. At Week 12 in EMBARQ-CSU1, 9.3% of placebo patients achieved complete response versus 42.4% on 150 mg and 42.1% on 300 mg (p<.00001 for both). In EMBARQ-CSU2, the rates were 12.6% for placebo, 45.7% for 150 mg and 44.0% for 300 mg (p<.00001 for both).
At Week 24, complete response rates in EMBARQ-CSU1 were 15.4% for placebo, 49.0% for 150 mg and 45.1% for 300 mg (p<.00001). In EMBARQ-CSU2, rates were 17.6% for placebo, 54.0% for 150 mg and 48.4% for 300 mg (p<.00001). These p-values were based on adjusted odds ratios from logistic regression models.
Benefit in Omalizumab-Refractory and Angioedema Populations
Among patients with CSU refractory to omalizumab, complete response at Week 12 in EMBARQ-CSU1 was 9.3% for placebo, 55.3% for 150 mg (p<.00001) and 44.3% for 300 mg (p=.00017). In EMBARQ-CSU2, the rates were 15.1% for placebo, 41.7% for 150 mg (p=.0089) and 46.4% for 300 mg (p=.0036).
In patients with baseline angioedema (搜索) activity score (AAS7) greater than zero, complete resolution of angioedema (AAS7=0) at Week 12 occurred in 33.8% of placebo patients in EMBARQ-CSU1 versus 62.7% on 150 mg and 66.3% on 300 mg (p<.00001 for both). In EMBARQ-CSU2, rates were 33.7% for placebo, 74.3% for 150 mg and 66.2% for 300 mg (p<.00001 for both).
"We are proud of the results shared today and believe that barzolvolimab has the potential to address the enormous unmet need in CSU," said Diane Young, MD, Senior Vice President and Chief Medical Officer of Celldex. She said barzolvolimab continued to show complete response rates across the overall studies and demonstrated differentiation in populations underserved by existing therapies, including patients with severe disease or angioedema (搜索) and those refractory to omalizumab.
"The results from our two Phase 3 EMBARQ-CSU trials showed efficacy that is best-in-disease in CSU," said Anthony Marucci, Co-Founder, President and Chief Executive Officer at Celldex. He said the company believes barzolvolimab is positioned as a first-line therapy for patients with severe CSU or angioedema (搜索) and as a second-line advanced therapy of choice.
Trial Design and Safety
Both Phase 3 trials were randomized, double-blind, placebo-controlled, parallel-group global studies. A total of 1,939 patients were randomized (n=963 in EMBARQ-CSU1; n=976 in EMBARQ-CSU2) evenly to barzolvolimab 150 mg every 4 weeks following a 300 mg loading dose, barzolvolimab 300 mg every 8 weeks following a 450 mg loading dose for 52 weeks, or placebo for 24 weeks. At 24 weeks, placebo patients were re-randomized to active treatment across both dosing groups.
The primary endpoint analysis was performed when all patients completed the placebo-controlled portion of the study at 24 weeks. The studies were designed to detect a clinically meaningful difference between each active arm and placebo in the overall population and in the omalizumab-refractory subpopulation.
Barzolvolimab was well tolerated with a favorable safety profile consistent with prior experience through the end of the placebo-controlled period at Week 24. Treatment continues in both trials through 52 weeks, and a global Phase 3b long-term extension study is ongoing for patients who complete the EMBARQ-CSU trials.
Mechanism and Development Plans
Barzolvolimab is a humanized monoclonal antibody that targets mast cells by binding with high specificity to a unique part of the KIT receptor (搜索) and inhibiting its activity. The KIT receptor is abundantly expressed by mast cells and is critical for their function and survival. Mast cell activation plays a central role in the onset and progression of chronic urticarias.
Based on randomized, placebo-controlled Phase 2 data, Celldex states that barzolvolimab has potential as a first-in-class treatment option for CSU, cold urticaria (搜索) (ColdU) and symptomatic dermographism (搜索) (SD). The antibody is being studied in Phase 3 trials in CSU and ColdU/SD and a Phase 2 study in atopic dermatitis (搜索), with additional indications planned.
Celldex intends to present the EMBARQ-CSU data at an upcoming medical meeting and plans to submit a Biologics License Application to the FDA in 2027.