Delgocitinib Cream Effective Over 16 Weeks for Chronic Hand Eczema

Robert Bissonnette, MD

Credit: Innovaderm Research

An announcement was made by LEO Pharma A/S, published in The Lancet, that new phase 3 findings from the DELTA 1 and DELTA 2 clinical trials indicated that delgocitinib cream had been superior to vehicle and well tolerated over 16 weeks among patients with chronic hand eczema.¹

The new research on this investigational topical pan-Janus kinase (JAK) inhibitor for moderate to severe chronic hand eczema was led by Robert Bissonnette, MD, lead author, chief executive officer and medical director of Innovaderm Research. The condition itself is known to persist for over 3 months and recur at least twice per-year.

“Historically, (chronic hand eczema) has been under researched, so the publication of the DELTA 1 and 2 trials in The Lancet is a positive step towards highlighting the condition, and in turn indicates the increased quality and rate of research in the space,” Bissonnette said in a statement. “Publication of milestones like this have a valuable role in our efforts to improve the day-to-day reality of those living with (chronic hand eczema).”²

For many individuals, hand eczema may become a chronic condition. It is known to impact around 9% of the population and is characterized by symptoms including pain, pruritus, scaling, lichenification, hyperkeratosis, fissures on patients’ hands and wrists, and others.

Delgocitinib cream is a drug which inhibits the JAK-STAT signaling pathway, a pathway which is linked to inflammation, dysfunction of the skin barrier, and shifts in patients’ skin microbiome. The pathway is essential to chronic hand eczema’s pathogenesis.

The cream was developed for moderate to severe chronic hand eczema and evaluated in the randomized, multi-center, double-blinded, vehicle-controlled DELTA 1 and 2 studies. The studies looked at patients with chronic hand eczema who had not responded adequately to, or could not utilize, topical corticosteroids.

These phase 3 trials’ primary aim was to assess the results of twice-per-day delgocitinib treatment. The investigators compared the medication’s safety and effectiveness versus a placebo cream used among adult patients, with the key measure of success being an Investigator’s Global Assessment (IGA) score for chronic hand eczema treatment (IGA-CHE TS) of 0 (clear) or 1 (almost clear) at the 16-week mark.

There would also have to have been at least a 2-step improvement from the point of baseline. The research team determined that additional scores would range from 2 (mild) to 4 (severe).

Their secondary endpoints would include itch and pain score reductions at the 16-week mark by 4 points minimum, evaluated through the Hand Eczema Symptom Diary (HESD). The investigators also looked at improvements of 75% and 90% from the point of baseline on the Hand Eczema Severity Index (HECSI).

In terms of safety endpoints, the primary one evaluated was the number of treatment-emergent adverse events from the point of baseline to the 16-week mark. Individuals who had been able to finish out the 16-week treatment period with delgocitinib or the vehicle cream were later invited to take part in their DELTA 3 open-label, multi-site extension trial. This extension study would take place over 36 weeks and was designed to assess the medication’s long-term safety results.

DELTA 2 and 2 Findings

DELTA 1 enrolled, from May 2021 - October 2022, 487 participants (181 men and 306 women). In DELTA 2, from May 2021 - January 2023, there were 473 participants enrolled (161 men and 312 women).

The research team concluded that a higher percentage of subjects treated with the cream had, by the 16-week mark, achieved success in IGA-CHE versus vehicle. The team noted that 20% had done so versus 10% in DELTA 1, and 29% had done so versus 7% in DELTA 2, with results being statistically significant (P ≤ .0055).

Adverse event occurrence was shown by the investigators to have been comparable between the delgocitinib and vehicle arms. They found occurrence rates to be 45% in DELTA 1 and 46% in DELTA 2 for delgocitinib, compared to rates of 51% and 45% in DELTA 1 and DELTA 2 for vehicle, respectively.

The research team concluded that the most common adverse events had been shown to be similar across both treatment cohorts, with the 2 most common having been COVID-19 and nasopharyngitis. The team later noted that the drug is still under investigation and has yet to receive approval from any health organizations.

References

1. ^{Bissonnette R, Warren RB, Schliemann S; trial investigators. Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials. Lancet. 2024 Jul 18:S0140-6736(24)01027-4. doi: 10.1016/S0140-6736(24)01027-4. Epub ahead of print. PMID: 39033766.}
2. ^{LEO Pharma Announces Publication of Chronic Hand Eczema Phase 3 Data in The Lancet. LEO Pharma. July 19, 2024. https://www.leo-pharma.com/media-center/news/2024-leo-pharma-announces-publication-of-chronic-hand-eczema-phase-3-data-in-the-lancet. Date accessed: July 26, 2024.}