Celldex Therapeutics (CLDX) Study result summary

Study design and patient population

• Two global, randomized, double-blind, placebo-controlled Phase 3 trials (EMBARQ-CSU1 and CSU2) enrolled 1,939 adults with moderate to severe, antihistamine-refractory chronic spontaneous urticaria (CSU) across 43 countries and 500+ sites.

• Patients included those with advanced therapy experience, omalizumab-refractory disease, and high rates of angioedema; over 60% had severe baseline disease (UAS7≥28).

• Patients were randomized to barzolvolimab 150 mg every 4 weeks (with 300 mg loading), 300 mg every 8 weeks (with 450 mg loading), or placebo for 24 weeks, then re-randomized to active treatment.

• The primary endpoint was mean change from baseline in weekly urticaria activity score (UAS7) at Week 12; key secondary endpoints included complete response rates (UAS7=0), angioedema control (AAS7=0), and efficacy in omalizumab-refractory subgroups.

• 84% of patients completed the 24-week placebo-controlled period; studies are ongoing with treatment continuing through 52 weeks and a long-term extension study available.

Efficacy results

• Barzolvolimab met the primary and all key secondary endpoints at both dose levels, with highly statistically significant and clinically meaningful reductions in disease activity.

• Mean UAS7 decreased by -20.2 to -20.5 on barzolvolimab vs. -10.7 to -11 on placebo at week 12 (p<0.00001).

• Complete response (UAS7=0) rates at week 12 were 42–46% for barzolvolimab vs. 9–13% for placebo, increasing to 54% at week 24.

• In omalizumab-refractory patients, complete response rates at week 12 were up to 55% for barzolvolimab vs. 9–15% for placebo.

• Up to 74% of patients with baseline angioedema achieved complete angioedema control (AAS7=0) at week 12, compared to 34% for placebo.

Safety and tolerability

• Barzolvolimab demonstrated a predictable, consistent, and well-tolerated safety profile, with most adverse events mild to moderate and reversible.

• Serious adverse event rates were similar between barzolvolimab and placebo (1%-2%).

• Common adverse events included hair color changes, skin pigmentation changes, and neutropenia; KIT-mediated effects were mild, reversible, and expected.

• No increase in infection rates or association between neutropenia and infection was observed; neutropenia events were mostly mild to moderate.

• Two cases of probable anaphylaxis occurred after the first dose among 2,400 treated patients; both recovered fully.