Celldex’s Barzolvolimab Shows Robust Phase III Efficacy in CSU; BLA Planned for 2027

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Based on the two Phase III trials

Celldex’s barzolvolimab met primary and key secondary endpoints in two Phase III CSU trials (EMBARQ‑CSU1 and EMBARQ‑CSU2). Both dose levels produced substantially larger UAS7 reductions at week 12 versus placebo, and complete response (UAS7 = 0) rates were meaningfully higher at weeks 12 and 24. The drug was well tolerated through 24 weeks, trials continue to 52 weeks, and Celldex plans a BLA filing in 2027. A prior Phase II failure in prurigo nodularis led to program termination in that indication and prompts caution ahead of an atopic dermatitis readout.

Celldex reported positive Phase III results for barzolvolimab, its anti‑KIT monoclonal antibody, in two pivotal chronic spontaneous urticaria (CSU) trials. The EMBARQ‑CSU1 and EMBARQ‑CSU2 studies met their primary and key secondary endpoints versus placebo in patients whose symptoms remained uncontrolled with H1‑antihistamines.

Topline Efficacy

Both trials achieved the primary endpoint of mean change from baseline in weekly urticaria activity score (UAS7) at week 12. In EMBARQ‑CSU1, the 150 mg arm recorded a −20.2 point change and the 300 mg arm a −20.5 point change, versus −10.7 points with placebo. EMBARQ‑CSU2 produced larger reductions: −29.7 points (150 mg) and −29.6 points (300 mg) versus −11.4 for placebo at week 12.

Key Secondary Outcomes

Complete response (UAS7 = 0) rates favored barzolvolimab at both week 12 and week 24. In EMBARQ‑CSU1, week‑12 complete responses were 42.4% (150 mg) and 42.1% (300 mg) versus 9.3% for placebo; by week 24 these rose to 49.0% and 45.1% versus 15.4% for placebo. EMBARQ‑CSU2 showed week‑12 rates of 45.7% (150 mg) and 44.0% (300 mg) versus 12.6% placebo, and week‑24 rates of 54.0%, 48.4% and 17.6%, respectively.

Other secondary endpoints also favored treatment: barzolvolimab improved outcomes in the omalizumab‑refractory CSU subgroup and increased the proportion of patients with a seven‑day angioedema activity score (AAS7) of zero at week 12 among those with baseline angioedema.

Safety and Ongoing Follow‑Up

Barzolvolimab was generally well tolerated during the 24‑week placebo‑controlled period. Both EMBARQ‑CSU trials remain active, with blinded or open‑label treatment continuing through 52 weeks to collect longer‑term efficacy and safety data.

Regulatory Pathway and Other Programs

Based on these data, Celldex plans to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration for CSU in 2027. Separately, Celldex discontinued development of barzolvolimab in prurigo nodularis after a negative Phase II, and that setback has prompted caution ahead of an upcoming atopic dermatitis readout.

Background

Chronic spontaneous urticaria is a condition of recurrent hives lasting six weeks or more, driven by immune‑mediated mast cell activation rather than classic allergen exposure. Barzolvolimab targets a portion of the KIT receptor, a critical regulator of mast cell function, aiming to reduce the inflammatory processes that drive CSU symptoms.