Celldex unveils Phase 2 results for hives drug and increased neutropenia rates

Celldex Therapeutics has recently revealed 52-week data from a mid-stage study of its anti-KIT drug, barzolvolimab, aimed at treating chronic hives, which has heightened expectations for its ongoing registrational studies. Barzolvolimab is currently undergoing two Phase 3 trials in patients with chronic spontaneous urticaria (CSU), following the positive topline data announced earlier in February. There is speculation among Wall Street analysts that Celldex could become a strong competitor to Novartis’ remibrutinib, which has already completed its registrational studies.

The newest results from Celldex show promising outcomes, with 71% of the 52 CSU patients receiving 150 mg of barzolvolimab every four weeks achieving a complete response, characterized by the absence of itch or hives, at the 52-week mark. Among the 51 patients who were administered 300 mg every eight weeks, just over half experienced a complete response. The company’s announcement did not provide p-values for these results.

Diane Young, Chief Medical Officer of Celldex, highlighted the significance of these findings, describing them as a pivotal moment for both the barzolvolimab program and the treatment of CSU. The clinical trials include patients who continue to exhibit symptoms despite antihistamine treatments. Notably, the responses were consistent regardless of patients' previous exposure to Xolair, a monoclonal antibody developed by Novartis and Genentech.

For comparative purposes, nearly 56% of participants who took Novartis' BTK inhibitor twice daily also achieved a complete response at 52 weeks in a Phase 2b extension trial for CSU. Following the release of favorable long-term Phase 3 data in May, Novartis has announced intentions to submit remibrutinib to regulatory agencies in the latter half of the year.

However, Celldex’s data revealed a higher incidence of neutropenia at 52 weeks, with 17% of patients affected, up from 9% in the earlier 16-week data. Neutropenia, a condition involving low levels of neutrophils, had been a major concern for investors prior to the Phase 2 trial, as noted by TD Cowen analysts in February. Despite this, Celldex clarified that neutrophil counts did not decrease further with continuous dosing in the latest Phase 2 data, and there was no connection found between neutropenia and infections.

Following the data release, Celldex’s shares experienced a significant drop, plunging by as much as 27%. The company did not report anaphylaxis issues, although approximately 8% of patients in the 150 mg group and 13% in the 300 mg group discontinued the treatment due to adverse events.

Earlier in February, Celldex shared topline Phase 2 results, which indicated that three doses, including the lowest dose of 75 mg, met the primary endpoint of mean change in urticaria activity score 7 (UAS7) at 12 weeks. Analysts from Cowen had described these results as “superb.”

The ongoing Phase 3 trials of barzolvolimab in CSU, launched in July, aim to enroll 915 patients each and will examine the efficacy of 150 mg and 300 mg doses. These studies employ the same primary endpoint as the Phase 2 trial.

Barzolvolimab is also being explored for other conditions such as prurigo nodularis, atopic dermatitis, and chronic inducible urticaria. Recently, GlobalData analysts projected that barzolvolimab could achieve $874 million in US sales by 2039.