LEO Pharma Initiates Phase 2a DELTA NEXT Trial of Delgocitinib Cream in Adults with Mild to Severe Palmoplantar Pustulosis (PPP)

Business Wire

6 days ago

BALLERUP, Denmark--(BUSINESS WIRE)--LEO Pharma A/S, a global leader in medical dermatology, today announced the initiation of the phase 2a proof-of-concept DELTA NEXT trial. The trial aims to evaluate the efficacy and safety of delgocitinib cream compared to cream vehicle in the treatment of adults with mild to severe Palmoplantar Pustulosis (PPP).
PPP is the first disease for which LEO Pharma will investigate delgocitinib cream since completion of the Phase 3 DELTA trials in Chronic Hand Eczema (CHE).
' The DELTA NEXT trial in PPP represents an exciting new chapter in the clinical development journey of delgocitinib cream,' said Christophe Bourdon, Chief Executive Officer, LEO Pharma. 'PPP is a disease with few treatment options that can severely affect quality of life. We are hopeful that this therapy could potentially provide much-needed help for patients suffering from this devastating condition.'
PPP is an uncommon, chronic, inflammatory, relapsing skin disease characterized by repeated episodes of sterile pustules alongside erythema, blistering and scaly skin on the palms and/or soles of the feet. 3,4 PPP is associated with a high patient burden, resulting in significant impairment of quality of life. Patients often experience pain, fatigue, and the condition can be triggered by factors such as smoking, infections, and stress. PPP is associated with comorbidities such as thyroid dysfunction and metabolic syndrome. 4
There are currently no approved advanced systemic treatments for PPP in the U.S. or Europe. 5 PPP is associated with complex T-cell activation patterns, which may be why many biologics that target individual T helper cell populations have shown limited efficacy in clinical trials. 6
Delgocitinib cream is a topical pan-Janus kinase (JAK) inhibitor shown to inhibit the activity of all four JAKs, which are involved in inflammatory signaling. 1,2 Using delgocitinib cream's mechanism of action, the trial will investigate the potential benefit of inhibiting multiple JAKs to treat PPP.
'I've seen firsthand how PPP can severely disrupt patients' lives, making it painful to walk, perform activities of daily living and impacting their ability to work,' said Dr. Robert Bissonnette, international coordinating investigator (ICI) on the DELTA NEXT trial and Chairman at Innovaderm Montreal, Canada. 'Despite the significant burden it places on patients, treatment options remain limited. There is a real and urgent need for effective therapies."
The DELTA NEXT trial plans to recruit up to 135 patients with active, chronic, mild to severe PPP for whom topical corticosteroids are inadequate or inadvisable. Participants will be recruited across 40-45 sites in the United States, Canada, the United Kingdom, Germany, and Poland.
Currently, delgocitinib cream is approved for adults in the European Union, United Kingdom, Switzerland, and the United Arab Emirates for the treatment of moderate to severe CHE for whom topical corticosteroids are inadequate or inappropriate, and is under review in other markets, including the United States.
For more information on the DELTA NEXT trial, go to clinicaltrials.gov.
Notes to editors
About Delgocitinib Cream
Delgocitinib cream is a topical pan-Janus kinase (JAK) inhibitor. It prevents the activation of the JAK-STAT pathway by blocking the signaling of several inflammatory cytokines, thereby suppressing the inflammatory cascade and preventing the downregulation of important barrier genes. 7
Delgocitinib cream is currently approved in the European Union, the United Kingdom, Switzerland and the United Arab Emirates for the treatment of moderate to severe Chronic Hand Eczema (CHE) in adults for whom topical corticosteroids are inadequate or inappropriate. It is under review in other markets, including the United States.
In 2014, LEO Pharma A/S and Japan Tobacco Inc. (JT) entered into a license agreement in which LEO Pharma gained exclusive rights to develop and commercialize delgocitinib cream for topical use in dermatological indications worldwide, excluding Japan, where JT retains rights.
About the DELTA NEXT Trial
DELTA NEXT is a phase 2a, randomized, double-blind, two-arm, vehicle control, adaptive design proof-of-concept trial to assess the efficacy and safety of twice-daily delgocitinib cream compared with cream vehicle in adult subjects with mild to severe PPP.
The DELTA NEXT trial plans to recruit up to 135 patients with active, chronic, mild to severe PPP for whom topical corticosteroids are inadequate or inadvisable. Participants will be randomized into a 2:1 ratio to receive either delgocitinib cream or cream vehicle. Participants will be recruited across 40-45 sites in the United States, Canada, the United Kingdom, Germany, and Poland.
About Palmoplantar Pustulosis (PPP)
Palmoplantar Pustulosis (PPP) is an uncommon chronic, inflammatory, relapsing skin disease characterized by repeated episodes of sterile pustules alongside erythema, blistering and scaly skin on the palms and/or soles of the feet. 3,4 The disease is more common in females, with the estimated prevalence ranging from 0.01% to 0.05%. 3,4 The mean age of patients ranges from 40 to 58 years and is often associated with smoking, thyroid-gland abnormalities, and nickel sensitivity. 4,8
PPP is associated with a significant clinical burden. Patients often experience pain, fatigue, and the condition can be associated with hyperlipidemia and high blood pressure. 8 The condition has been shown to have a greater impairment on work and daily life than plaque psoriasis. 8
About LEO Pharma
LEO Pharma is a global leader in medical dermatology. We deliver innovative solutions for skin health, building on a century of experience with breakthrough medicines in healthcare. We are committed to making a fundamental difference in people's lives, and our broad portfolio of treatments serves close to 100 million patients in over 70 countries annually. Headquartered in Denmark, LEO Pharma has a team of 4,000 people worldwide. LEO Pharma is co-owned by majority shareholder the LEO Foundation and, since 2021, Nordic Capital. For more information, visit www.leo-pharma.com.
References
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Tanimoto A, Shinozaki Y, Yamamoto Y, et al. A novel JAK inhibitor JTE-052 reduces skin inflammation and ameliorates chronic dermatitis in rodent models: Comparison with conventional therapeutic agents. Exp Dermatol. 2018;27(1):22-29.
Kharawala S, Golembesky AK, Bohn RL, Esser D. The clinical, humanistic, and economic burden of generalized pustular psoriasis: a structured review. Expert Rev Clin Immunol. 2020;16(3):239-252.
Misiak-Galazka M, Zozula J, Rudnicka L. Palmoplantar Pustulosis: Recent Advances in Etiopathogenesis and Emerging Treatments. Am J Clin Dermatol. 2020;21(3):355-370.
Xu JM, Wang HM, Jin HZ. An update on therapeutic options for palmoplantar pustulosis: a narrative review and expert recommendations. Expert Rev Clin Immunol. 2023;19(5):499-516.
McCluskey D, Benzian-Olsson N, Mahil SK, et al. Single-cell analysis implicates TH17-to-TH2 cell plasticity in the pathogenesis of palmoplantar pustulosis. J Allergy Clin Immunol. 2022;150(4):882-893.
Dubin C, Del Duca E, Guttman-Yassky E. Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges [published correction appears in Ther Clin Risk Manag. 2021 Mar 18;17:233.]. Ther Clin Risk Manag. 2020;16:1319-1332.
Lebwohl MG, Medeiros RA, Strober B, et al. Palmoplantar Pustulosis has a Greater Disease Burden than Plaque Psoriasis: Real-World Evidence From the CorEvitas Psoriasis Registry. J Psoriasis Psoriatic Arthritis. 2023;8:56–65.