Celldex barzolvolimab Phase 3 trials meet endpoints but report two anaphylaxis cases

Celldex Therapeutics announced positive topline results from its Phase 3 EMBARQ-CSU1 and EMBARQ-CSU2 trials of barzolvolimab, meeting all primary and key secondary endpoints for chronic spontaneous urticaria. However, Celldex shares fell up to 15% on September 22, 2026, as investors focused on two cases of probable anaphylaxis. Despite safety concerns, analysts highlighted the drug's best-in-disease efficacy, and Celldex plans to submit a Biologics License Application to the FDA in 2027.

Primary efficacy endpoint results

• ▪Celldex Therapeutics announced that its Phase 3 EMBARQ-CSU1 and EMBARQ-CSU2 trials of barzolvolimab in patients with chronic spontaneous urticaria met their primary endpoint of mean change from baseline in weekly urticaria activity score at Week 12.
• ▪In the EMBARQ-CSU1 trial, the 150 mg dose of barzolvolimab showed a mean change in weekly urticaria activity score of -20.2 at Week 12 compared to -10.7 for placebo, while the 300 mg dose showed a mean change of -20.5.

Efficacy in patient subgroups

• ▪Among patients with baseline angioedema in the Phase 3 trials, 62.7% to 74.3% achieved complete resolution compared to approximately 33% on placebo.
• ▪Barzolvolimab demonstrated clinical benefit in patients with chronic spontaneous urticaria whose disease was refractory to omalizumab and in patients with baseline severe angioedema.

Anaphylaxis cases and safety response

• ▪Celldex Therapeutics Chief Executive Officer Anthony Marucci stated that the incidence of anaphylaxis was extremely low among approximately 2,400 patients treated with barzolvolimab overall.
• ▪Celldex Therapeutics expects any approved regulatory label for barzolvolimab to include warnings and precautions related to hypersensitivity and anaphylaxis, similar to other biologics.
• ▪Two cases of probable anaphylaxis were confirmed following barzolvolimab treatment in the Phase 3 trials, with one patient requiring hospitalization and the other treated at the clinic and discharged.

Analyst commentary and outlook

• ▪Cantor Fitzgerald analyst Kristen Kluska forecasted that peak sales of barzolvolimab could reach $4.8 billion, noting that its efficacy looks to be the best Phase 3 data set across pivotal studies.
• ▪Cantor Fitzgerald analyst Kristen Kluska suggested that physicians might choose to administer the first dose of barzolvolimab in clinics to monitor patients for potential issues.

Trial design and randomization

• ▪The Phase 3 EMBARQ-CSU1 and EMBARQ-CSU2 trials randomized 1,939 patients, with 963 patients in EMBARQ-CSU1 and 976 patients in EMBARQ-CSU2.
• ▪In the Phase 3 EMBARQ-CSU trials, patients on placebo were re-randomized to active treatment across both dosing groups at 24 weeks.

Trial continuation and extension

• ▪Celldex Therapeutics has established an ongoing global Phase 3b long-term extension study that patients can enter after completing the EMBARQ-CSU Phase 3 trials.
• ▪The Phase 3 EMBARQ-CSU trials are ongoing, with patient treatment continuing through 52 weeks.

Debatable claims

• ▪Barzolvolimab's clinical efficacy outweighs the safety risks of its reported anaphylaxis cases
• ▪The stock market overreacted to the safety concerns in Celldex's clinical trials
• ▪The FDA should restrict barzolvolimab to a last-line therapy for chronic hives