Celldex Therapeutics Scraps PN Plans After Barzolvolimab Phase 2 Miss

Celldex Therapeutics NASDAQ: CLDX said a Phase 2 trial of barzolvolimab in prurigo nodularis did not meet its primary or secondary endpoints, prompting the company to discontinue development of the drug in that indication while continuing to focus on ongoing late-stage urticaria studies.

Anthony Marucci, Celldex’s co-founder, president and chief executive officer, said the company was “disappointed” by the results, which showed barzolvolimab produced “profound systemic depletion of mast cells” but did not translate into improvements in itch or skin lesions for patients with prurigo nodularis, or PN.

“Unlike our intravenous Phase 1 study, this Phase 2 subQ study did not result in improvements in itch or skin lesions for patients, indicating that mast cells may not be the key pathogenic driver of symptoms in PN,” Marucci said.

Dr. Diane Young, Celldex’s senior vice president and chief medical officer, said the randomized, double-blind, placebo-controlled study enrolled 140 participants across six countries and 48 sites. Patients had moderate to severe PN and had either an inadequate response to prescription topical medications or were unable to use them for medical reasons. Participants were assigned to placebo or one of two subcutaneous barzolvolimab dosing regimens: 150 milligrams or 300 milligrams every four weeks after an initial 450 milligram loading dose. The placebo-controlled treatment period lasted 24 weeks, followed by a 16-week follow-up period through week 40, with an option for an open-label extension.

The primary endpoint was the proportion of participants achieving at least a four-point improvement in the Worst Itch Numeric Rating Scale at 12 weeks. Young said patients entered the trial with a mean baseline score greater than 8 on the 0-to-10 itch scale.

“Patients treated with barzolvolimab did not have differentiated responses compared to placebo across either dose or at any of the time points,” Young said. She added that key secondary endpoints, including an investigator assessment of skin lesions and a combined itch and lesion endpoint, also failed to show differentiation from placebo.

Celldex had advanced barzolvolimab into the Phase 2 PN trial after a small 23-patient Phase 1b study using intravenous administration showed positive signals in itch reduction and nodule resolution at the highest dose tested. Young said the company is still reviewing the new data and plans to analyze biopsy samples in the coming months to better understand the discrepancy between the Phase 1b and Phase 2 results. She noted that the Phase 2 trial was larger and used subcutaneous administration rather than intravenous dosing.

“IV administration is associated with more rapid and higher drug concentrations relative to subQ,” Young said. “We can’t rule out that these differences may have contributed to the difference in outcome.” However, she said both studies achieved profound decreases in circulating tryptase, a marker Celldex uses to assess mast cell depletion. Based on the current data, she said the company’s assessment is that mast cells may not be a key pathogenic driver of PN symptoms.

Despite the efficacy miss, Celldex said barzolvolimab was well tolerated in the PN study and that the safety profile was consistent with prior trials. Young said the trial tested the highest subcutaneous exposure studied to date with the 450 milligram loading dose followed by 300 milligrams every four weeks. The most frequently reported adverse events occurring in more than 10% of participants in any treatment group were hair color changes and nasopharyngitis, all of which were G...