Celldex Therapeutics said barzolvolimab met the primary endpoint and all key secondary endpoints in both Phase 3 EMBARQ-CSU trials, with complete response rates of 42.1% to 45.7% at Week 12 versus 9.3% to 12.6% for placebo. The 1,939-patient program also showed benefit in omalizumab-refractory patients and those with angioedema. Shares fell more than 20% in premarket trading, and Celldex still plans a 2027 BLA filing.
Celldex Therapeutics said its experimental antibody barzolvolimab met the primary endpoint and every key secondary goal in two Phase 3 trials in chronic spontaneous urticaria, then watched its shares fall more than 20% in premarket trading on Tuesday.
"We believe that barzolvolimab can be a transformational therapy for people living with CSU," Diane Young, Senior Vice President and Chief Medical Officer at Celldex, said in the company's statement. Chief Executive Anthony Marucci called the efficacy "best-in-disease in CSU" and said the company is moving to build a commercial-stage organization.
The EMBARQ-CSU1 and EMBARQ-CSU2 studies randomized 1,939 patients — 963 and 976 respectively — to barzolvolimab 150 mg every four weeks, 300 mg every eight weeks, or placebo. Both dose groups beat placebo on the primary measure, mean change from baseline in the weekly urticaria activity score (UAS7) at Week 12. In EMBARQ-CSU1, the 150 mg arm improved 20.2 points versus 10.7 for placebo; in EMBARQ-CSU2, the 300 mg arm improved 19.7 points versus 11.4. Every comparison carried a p-value below .00001, meaning the odds the results were random are under one in 100,000.
Complete response — the total absence of itch and hives, or UAS7=0 — reached 42.1% to 45.7% across the two doses and two studies at Week 12, against 9.3% to 12.6% for placebo. By Week 24 the active arms held 45.1% to 54.0% complete response rates versus 15.4% to 17.6% on placebo, showing the benefit deepened rather than faded after the 12-week readout.
The differentiation sits in the hardest-to-treat groups. Among patients refractory to omalizumab — the standard advanced therapy sold by Novartis and Roche as Xolair — complete response at Week 12 ranged from 41.7% to 55.3% on barzolvolimab versus 9.3% to 15.1% on placebo. In patients who entered with angioedema, complete resolution of swelling reached 62.7% to 74.3% on the drug against roughly 34% on placebo.
Barzolvolimab is a humanized monoclonal antibody that binds a unique region of the KIT receptor, blocking the signaling mast cells need to survive. Mast cell activation drives the itch and hives of CSU, a condition that affects an estimated 1% of the global population and leaves a meaningful share of patients uncontrolled on H1-antihistamines. The safety profile through the 24-week placebo-controlled period matched prior Phase 2 experience, the company said, with no new signals disclosed.
Celldex plans to present the full EMBARQ-CSU dataset at an upcoming medical meeting and to file a Biologics License Application with the FDA in 2027. Treatment continues in both trials through 52 weeks, and a Phase 3b long-term extension study is enrolling. The program also spans Phase 3 work in cold urticaria and symptomatic dermographism and a Phase 2 study in atopic dermatitis, where it would compete with Dupixent from Sanofi and Regeneron.
The premarket decline puts the readout in the same category as several 2026 biotech catalysts where strong efficacy failed to clear a bar set by elevated expectations. Investors will watch two things from here: whether the 52-week data and the medical-meeting presentation resolve questions about durability and dosing convenience, and whether the 2027 BLA filing stays on schedule. The company has not yet disclosed a peak sales estimate for barzolvolimab.
This article is for informational purposes only and does not constitute investment advice.
