Celldex’s subcutaneous monoclonal antibody (mAb) has failed to show benefit in a Phase II prurigo nodularis (PN) trial.
In the randomised, double-blind, placebo-controlled, parallel group Phase II study (NCT06366750), patients treated with barzolvolimab failed to show significant four-point improvement on the Worst Itch Numeric Rating Scale (WI-NRS) from baseline to week 12 compared to placebo. Along with this miss, key secondary endpoints, including patients with IGA-CPNG-S 0/1 (Investigator’s Global Assessment for Chronic Nodular Prurigo – Stage) did not differentiate from placebo.
Barzolvolimab, a humanised mAb, did not result in improvement in itch or skin lesions in patients with PN compared to placebo, indicating mast cells may not be a key pathogenic driver of symptoms in PN.
The drug targets mast cells by binding with high specificity to a unique part of the KIT receptor and potently inhibiting its activity. The KIT receptor is abundantly expressed by mast cells and critical for their function and survival. The trial did show rapid and profound suppression of circulating tryptase, indicative of systemic mast cell depletion, showing the drug was indeed hitting its target. However, even over a longer, 24 week treatment period, no benefit was seen.
Based on this trial failure, Celldex is discontinuing the Phase II study in PN. The company added, however, that consistent with previously reported studies, barzolvolimab demonstrated a favourable safety and tolerability profile, supporting its continued development in other indications.
Anthony Marucci, CEO of Celldex, said: “Barzolvolimab profoundly depletes mast cells with best-in-disease data observed in three indications to date; chronic spontaneous urticaria, symptomatic dermographism, and cold urticaria, all of which demonstrated unequivocal Phase II proof-of-concept data and progressed quickly to Phase III. It is disappointing that this study did not confirm the promising signal we observed in the intravenous Phase Ib trial, and that the robust tryptase reductions seen in this study did not result in improvement of PN symptoms for patients who greatly need effective treatments.”
In response to the readout, Celldex’s stock is set to drop upon market open today, according to premarket estimates. The companies stock closed at $35.66 on 21 July and is currently estimated to open 7.74% down at $32.90 (correct at 4.21am ET). The company, listed on the Nasdaq exchange, has a market cap of $2.79bn.
This will come as a blow for patients, too, as there are many unmet needs in PN, spanning clinical, psychological, and physiological domains. Primarily, the challenge is a lack of targeted long-term treatments, profound psychological impacts, including high rates of anxiety, depression, and suicidal ideation, and the failure of traditional anti-inflammatory and topical therapies to break the relentless itch-scratch cycle.
Historically, PN has been managed using broad-spectrum, off-label immunosuppressants, systemic therapies, or high-potency topical steroids. These treatments often demonstrate inadequate efficacy, and some have unfavourable long-term safety profiles – such as organ toxicity or skin atrophy.
Sanofi and Regeneron’s Dupixent (dupilimab) is one of a handful of disease modifying therapies (DMTs) available for PN.
Galderma’s mAb Nemluvio (nemolizumab-ilto), has shown long term benefit, with data from week 100 of a long-term extension trial demonstrating significant symptom improvements, with over 90% and 70% of subjects achieving a minimum four-point improvement in itch and being itch-free or nearly itch-free, respectively. Also, a minimum of 80% of patients showed healing of skin lesions.
According to a GlobalData report, across the 16 major pharmaceutical markets (16MM: Australia, Brazil, Canada, China, France, Germany, India, Italy, Japan, Mexico, Russia, South Africa, South Korea, Spain, UK, and US), epidemiologists estimate that there will be 1,467,290 diagnosed cases of PN in 2029, up from an estimated 1,437,305 in 2024.
GlobalData is the parent company of Clinical Trials Arena.
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