Celldex Therapeutics reported topline results from the phase 3 EMBARQ-CSU1 and EMBARQ-CSU2 trials of barzolvolimab (CDX-0159), showing the anti-KIT monoclonal antibody met the primary endpoint of mean change from baseline in weekly urticaria activity score (UAS7) at Week 12 in patients with antihistamine-refractory chronic spontaneous urticaria (CSU).¹
The EMBARQ-CSU program is among the largest conducted in antihistamine-refractory CSU, enrolling patients with advanced therapy experience, including those refractory to omalizumab.¹ Celldex plans to submit a biologics license application to the FDA in 2027, positioning barzolvolimab as a potential first-line option for severe CSU or angioedema and a second-line option following omalizumab.¹
"Barzolvolimab continued to show unprecedented complete response rates across the overall studies and demonstrated strong differentiation in patient populations underserved by existing therapies, including those with severe disease or angioedema, and those whose disease is refractory to omalizumab," Diane Young, MD, senior vice president and chief medical officer, Celldex, said in a statement.
Barzolvolimab Efficacy in EMBARQ-CSU1 and EMBARQ-CSU2
EMBARQ-CSU1 and EMBARQ-CSU2 are randomized, double-blind, placebo-controlled, parallel-group global phase 3 trials evaluating barzolvolimab in adults with CSU inadequately controlled by H1-antihistamines.¹ The studies randomized 1939 patients evenly, 963 in EMBARQ-CSU1 and 976 in EMBARQ-CSU2, 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, or placebo for 24 weeks.¹ Patients assigned to placebo were re-randomized to active treatment at Week 24, with both dosing groups continuing therapy through 52 weeks.¹
Both trials met the primary endpoint at Week 12.¹ In EMBARQ-CSU1, the 150 mg dose reduced UAS7 by a least-squares mean of 20.2 points (SE, 0.64) versus 10.7 points (SE, 0.65) with placebo (P < .00001), and the 300 mg dose reduced UAS7 by 20.5 points (SE, 0.65) versus placebo (P < .00001).¹ In EMBARQ-CSU2, the 150 mg dose produced a 20.2-point reduction (SE, 0.63) and the 300 mg dose a 19.7-point reduction (SE, 0.64), both versus an 11.4-point placebo reduction (SE, 0.64; P < .00001 for each comparison).¹
Barzolvolimab Secondary Endpoints and Safety in CSU
Key secondary endpoints centered on complete response, defined as UAS7 of 0, or complete absence of itch and hives.¹ At Week 12, complete response rates reached 42.4% (150 mg) and 42.1% (300 mg) in EMBARQ-CSU1 and 45.7% (150 mg) and 44.0% (300 mg) in EMBARQ-CSU2, compared with 9.3% and 12.6% with placebo, respectively (P < .00001 for all comparisons).¹ By Week 24, complete response rates rose further, reaching 49.0% and 45.1% in EMBARQ-CSU1 and 54.0% and 48.4% in EMBARQ-CSU2 across the 150 mg and 300 mg arms.¹
In the omalizumab-refractory subgroup, complete response at Week 12 ranged from 44.3% to 55.3% across doses and trials versus 9.3% to 15.1% with placebo (P = .0036 to P < .00001).¹ Among patients with baseline angioedema activity, complete resolution of angioedema (AAS7 of 0) at Week 12 occurred in 62.7% to 74.3% of barzolvolimab-treated patients versus 33.7% to 33.8% with placebo (P < .00001 for all comparisons).¹ Celldex reported barzolvolimab was well tolerated through the 24-week placebo-controlled period, with a safety profile consistent with prior phase 2 experience and no new signals disclosed.¹
"We believe barzolvolimab is well-positioned to address large CSU populations of high unmet need, as a first-line therapy for patients with severe CSU or angioedema, and as the second-line advanced therapy of choice," said Anthony Marucci, co-founder, president, and chief executive officer, Celldex.
Beyond CSU, barzolvolimab is in phase 3 development for cold urticaria and symptomatic dermographism, with a phase 2 trial ongoing in atopic dermatitis.¹ A global phase 3b long-term extension study is also underway for patients who complete the EMBARQ-CSU program.¹
Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.
References
Celldex Therapeutics. Celldex announces positive results from phase 3 EMBARQ-CSU1 and EMBARQ-CSU2 studies of barzolvolimab which met primary and all key secondary endpoints. Published September 22, 2026. Accessed September 22, 2026. https://www.celldex.com.
ClinicalTrials.gov. A study to assess the safety and efficacy of barzolvolimab in chronic spontaneous urticaria (EMBARQ-CSU1). NCT06445023. Accessed September 22, 2026.
ClinicalTrials.gov. A study to assess the safety and efficacy of barzolvolimab in chronic spontaneous urticaria (EMBARQ-CSU2). NCT06455202. Accessed September 22, 2026.
