Initiation of phase III program for barzolvolimab in patients with chronic spontaneous urticaria

The studies will also include patients who remain symptomatic after treatment with biologics.

For patients with CSU, the activation of mast cells in the skin results in episodes of itchy hives, swelling and inflammation of the skin that can severely impact their daily lives for years or even decades. Treatment options are limited, particularly for patients not adequately controlled by omalizumab.

Barzolvolimab, a novel monoclonal antibody, works upstream of other treatment approaches for CSU, targeting the root driver of the disease—mast cells—by blocking the receptor tyrosine kinase KIT, which is required for mast cell function and survival.

“Across multiple studies in CSU, barzolvolimab has demonstrated a unique and profound ability to offer rapid, durable and complete disease control, regardless of prior treatment history, to patients suffering from this often severe and debilitating disease,” said Marcus Maurer, MD, Professor of Dermatology and Allergy at Charité – Universitätsmedizin in Berlin and a Principal Investigator in the Phase 3 studies of barzolvolimab. “Advancing a promising agent that addresses the root driver of the disease—the mast cell—into late stage studies is a significant and hopeful step forward for patients and physicians who desperately need better treatment options.”

EMBARQ-CSU1 and EMBARQ-CSU2 are designed to establish the efficacy and safety of barzolvolimab in adult patients with CSU who remain symptomatic despite H1 antihistamine treatment. Both Phase III trials are randomized, double-blind, placebo-controlled, parallel group, global studies where approximately 915 patients will be randomized evenly to barzolvolimab 150 mg every 4 weeks (following 300 mg loading dose), barzolvolimab 300 mg every 8 weeks (following 450 mg loading dose) or placebo for 52 weeks. At 24 weeks, patients on placebo will be re-randomized to active treatment across both dosing groups. The primary endpoint of the study will evaluate the clinical effect of barzolvolimab in reducing urticaria activity (weekly urticaria activity score; UAS7) at Week 12. The study is designed to detect a clinically meaningful difference between each of the active arms vs placebo in the overall population as well as in the subpopulation of omalizumab refractory participants.

“Treatment options that deliver complete disease control for more patients are sorely needed in CSU and advancing barzolvolimab into registrational studies is an important step forward for patients,” said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. “We are focused on executing these trials seamlessly and achieving our goal of making barzolvolimab available to meet the needs of patients with CSU, while also advancing barzolvolimab across additional indications.”

Results from a placebo controlled Phase II study in CSU demonstrated that barzolvolimab met the primary endpoint of the study, a statistically significant mean change from baseline to week 12 in UAS7, across all dose levels. Secondary and exploratory endpoints in the study were also achieved at week 12 and strongly support the primary endpoint results, including changes in ISS7 (weekly itch severity score) and HSS7 (weekly hives severity score) and responder analyses (UAS7<=6 or uas7="0)." importantly, barzolvolimab demonstrated rapid, durable and clinically meaningful responses in patients with moderate to severe csu refractory to antihistamines, including patients with prior omalizumab treatment and was well tolerated with a favorable safety profile.