Celldex Therapeutics (NASDAQ:CLDX) reported positive top-line results from its two Phase III EMBARQ-CSU studies of barzolvolimab in adults with chronic spontaneous urticaria, or CSU, who remained symptomatic despite H1 antihistamine treatment. The company said both evaluated dose regimens met the primary endpoint and all key secondary endpoints, with efficacy sustained or deepening through 24 weeks.
The global, randomized, double-blind, placebo-controlled trials enrolled 1,939 patients across more than 500 sites in 43 countries. A total of 1,935 patients received treatment, with participants assigned to either 150 mg of barzolvolimab every four weeks following a 300 mg loading dose, 300 mg every eight weeks following a 450 mg loading dose, or placebo for 24 weeks.
Primary Endpoint Met in Both Studies
The primary endpoint was the mean change from baseline in weekly urticaria activity score, known as UAS7, at week 12. UAS7 is a patient-reported measure of itch and hive severity.
According to Chief Medical Officer Diane Young, both barzolvolimab regimens showed clinically meaningful and statistically significant improvements compared with placebo in each trial. Mean UAS7 declines were approximately 20 points in barzolvolimab-treated patients, compared with about 10 points in the placebo group, with p-values below 0.00001.
Anthony Marucci, Celldex’s co-founder, president and chief executive officer, said the results demonstrated “rapid, profound, and durable efficacy” across the studies. During the question-and-answer session, management said treatment responses were observed by at least two weeks, while noting that it continues to analyze the full timing-of-response data.
The company reported that up to 46% of patients achieved a complete response, defined as a UAS7 score of zero, at week 12. That rate increased to up to 54% at week 24. A UAS7 score of zero represents the absence of itch and hives.
Results in Refractory Disease and Angioedema
Celldex highlighted results in patients whose disease was refractory to omalizumab, defining that group as patients who did not respond to approved-dose omalizumab after at least three months, lost an initial response, or discontinued the therapy because of intolerance. The studies enrolled 288 omalizumab-refractory patients.
Up to 55% of omalizumab-refractory patients achieved a complete response at week 12, according to the company. Young said the trials were the first Phase III CSU studies to demonstrate efficacy in an omalizumab-refractory population.
The company also reported results in patients with angioedema, a form of swelling that can accompany CSU. Among patients with angioedema at baseline, up to 74% achieved complete angioedema control at week 12, measured by an angioedema activity score of zero.
Celldex said roughly two-thirds of enrolled patients had severe CSU at baseline, while more than two-thirds had angioedema. The company characterized the trial population as having substantial disease burden and quality-of-life impairment.
Safety Profile Remained Consistent With Earlier Studies
The pooled placebo-controlled safety analysis covered nearly 2,000 patients over 24 weeks. Celldex said the majority of adverse events were mild to moderate and that no new meaningful safety signals were identified.
Young said serious adverse-event rates were similar between placebo and barzolvolimab groups, and the company reported no increase in Grade 3 or Grade 4 adverse events relative to placebo. Infection rates, including serious infections, were balanced between treatment and placebo groups, Celldex said, and management reported no association between neutropenia and infections.
Neutropenia was reported as an adverse event in 9.1% of patients receiving the 150 mg regimen and 11.7% of those receiving the 300 mg regimen. The company said these events were mostly mild to moderate.
There were two cases of probable anaphylaxis following a first barzolvolimab dose across the Phase III studies, as adjudicated by an independent committee. One event occurred about 10 minutes after dosing and the other occurred about 2.5 hours after dosing; both patients recovered. Celldex said these were the only two adjudicated probable anaphylaxis cases across its subcutaneous barzolvolimab program, encompassing more than 2,400 treated patients.
The overall discontinuation rate during the placebo-controlled period was 16%, including an approximately 8% rate of discontinuations related to adverse events, according to management. The company cited hair-color changes, skin-pigment changes and neutropenia among the more common causes, while describing these effects as consistent with KIT inhibition and generally reversible based on earlier studies.
Commercial and Regulatory Plans
Celldex intends to seek approval for both dosing regimens, Regulatory Affairs and Quality Senior Vice President Margo Heath-Chiozzi said, citing the company’s goal of providing treatment optionality. The company said it has discussed its development program with regulators and has more than 500 patients treated for up to one year.
Teri Lawver, senior vice president and chief commercial officer, said the company expects healthcare-provider office administration to be the initial launch model. Celldex is also planning for an autoinjector option for at-home administration around 18 months after an initial approval.
Management said it views barzolvolimab as a potential treatment for patients with severe CSU or severe angioedema as well as those who remain symptomatic after existing advanced therapies. Celldex also said it expects to report Phase II results in atopic dermatitis during the fourth quarter and that its Phase III CSU and cold urticaria programs remain on track.
About Celldex Therapeutics (NASDAQ:CLDX)
Celldex Therapeutics, Inc is a clinical-stage biopharmaceutical company focused on developing antibody-based therapeutics for diseases with significant unmet medical needs. The company’s research programs address conditions in immunology, inflammation, oncology and other areas where targeted immune-system modulation may provide therapeutic benefits.
Celldex’s lead investigational product is barzolvolimab, an antibody designed to block the KIT receptor and reduce mast cells. The therapy is being studied in immune-mediated diseases, including chronic spontaneous urticaria and prurigo nodularis.
