LEO Pharma has achieved a significant regulatory milestone with the FDA's acceptance of its New Drug Application (NDA) for delgocitinib cream, a potential breakthrough treatment for adults suffering from moderate to severe chronic hand eczema (CHE). This investigational topical cream, a pan-Janus kinase (JAK) inhibitor, could become the first FDA-approved therapy specifically indicated for CHE, addressing a critical unmet need in dermatology.
The FDA's decision is based on data from the Phase 3 DELTA 1 and DELTA 2 clinical trials, which evaluated the safety and efficacy of delgocitinib cream compared to a vehicle cream. Both trials met their primary endpoints, demonstrating statistically significant improvements in Investigator's Global Assessment (IGA) scores for CHE treatment success (IGA-CHE TS). Specifically, DELTA 1 showed that 20% of patients treated with delgocitinib achieved IGA-CHE TS compared to 10% in the vehicle arm, while DELTA 2 showed 29% versus 7%, respectively (P ≤ .0055).
Clinical Significance
Chronic Hand Eczema (CHE) is a debilitating condition affecting approximately 4.7% to 9% of the population globally, characterized by intense itching, pain, and inflammation of the hands and wrists. The condition significantly impacts patients' quality of life, affecting their ability to work, perform daily activities, and maintain social relationships. Current treatment options, primarily topical corticosteroids, often provide inadequate relief or are associated with adverse effects with long-term use.
"Dermatologists regularly see the true extent to which CHE impacts patients’ lives through unique physical and psychological challenges," said Christopher Bunick, MD, PhD, Associate Professor of Dermatology at Yale Medical School. "Many patients need more options beyond traditional topical corticosteroid use, so I welcome today’s news, which brings the prospect of a potential new treatment option one step closer for those across the U.S. living with this debilitating condition."
DELTA 1, 2, and 3 Trials
The DELTA 1 and DELTA 2 trials were randomized, double-blind, vehicle-controlled, multi-center Phase 3 clinical trials designed to assess the efficacy of twice-daily applications of delgocitinib cream 20 mg/g (2%) compared to a vehicle cream in adults with moderate to severe CHE. The primary endpoint was the Investigator’s Global Assessment for Chronic Hand Eczema treatment success (IGA-CHE TS) at Week 16, defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with at least a two-step improvement from baseline.
Key secondary endpoints at Week 16 included reduction of itch and pain scores of ≥4 points measured by the Hand Eczema Symptom Diary (HESD) from baseline to Week 16, as well as at least 75% improvement from baseline and at least 90% improvement from baseline on the Hand Eczema Severity Index (HECSI) at Week 16. The number of treatment-emergent adverse events from baseline to Week 16 defined the key safety endpoint of the trials.
Participants who completed the 16-week DELTA 1 or DELTA 2 trials were offered enrollment in the 36-week DELTA 3 open-label extension trial to evaluate the long-term safety of delgocitinib.
Mechanism of Action
Delgocitinib cream is an investigational topical pan-JAK inhibitor that inhibits the activation of JAK-STAT signaling, which plays a key role in the pathogenesis of CHE. The pathophysiology of CHE involves skin barrier dysfunction, skin inflammation, and alterations of the skin microbiome.
Looking Ahead
The FDA's regulatory review process is expected to conclude in the second half of 2025. If approved, delgocitinib cream would represent a significant advancement in the treatment of chronic hand eczema, offering a targeted therapy to address the underlying inflammatory pathways involved in the disease.
