LEO Pharma Presents Late-Breaking Positive Phase 3 Results of Delgocitinib Cream in Adults with Moderate to Severe Chronic Hand Eczema (CHE) at AAD 2023

• Results demonstrated that delgocitinib cream provided statistically significant improvements in primary and all key secondary endpoints, which included both clinician-assessed and patient-reported efficacy outcomes compared to cream vehicle.¹
• Delgocitinib cream showed a statistically significant treatment effect compared to cream vehicle as early as four weeks after initiation of treatment.¹

BALLERUP, Denmark--(BUSINESS WIRE)--LEO Pharma A/S, a global leader in medical dermatology, today presented positive results from the DELTA 1 trial in one of two LEO Pharma late-breaking sessions at the American Academy of Dermatology (AAD) 2023 Annual Meeting.¹ DELTA 1 is a pivotal phase 3 clinical trial with delgocitinib cream, an investigational topical pan-Janus kinase (JAK)-inhibitor for the potential treatment of adults with moderate to severe chronic hand eczema (CHE).² The safety and efficacy of delgocitinib cream is under investigation and has not been evaluated by any health authority.

The DELTA 1 trial randomized 487 adults with moderate-to-severe CHE to twice-daily delgocitinib cream 20 mg/g (n=325) or cream vehicle (n=162) for 16 weeks followed by a 36-week extension trial. The primary endpoint was the proportion of patients with moderate to severe CHE who achieved an Investigator’s Global Assessment (IGA)-CHE score of 0 (clear) or 1 (almost clear: barely perceptible erythema only) with a ≥2 point improvement from baseline at Week 16. A significantly greater proportion of delgocitinib-treated patients, compared to cream vehicle, achieved this IGA-CHE improvement (19.7% vs. 9.9%; p=0.006). Similar differences were observed at Week 4 (15.4% vs. 4.9%; p<0.001) and Week 8 (22.8% vs. 10.5%; p=0.001).¹

The trial also achieved its key secondary endpoints at Week 16. A significantly greater proportion of delgocitinib-treated patients achieved a ≥75% improvement in Hand Eczema Severity Index (HECSI-75) compared to cream vehicle (49.2% vs. 23.5%; p<0.001). A similar trend was observed in those achieving a ≥90% improvement (HECSI-90) (29.5% vs. 12.3%; p<0.001).¹

The Dermatology Life Quality Index (DLQI) was another key secondary endpoint used to measure patient-reported efficacy. A ≥4-point improvement was observed in 74.4% of delgocitinib-treated patients compared to 50.0% for cream vehicle (p<0.001).¹

Over the 16-week trial period, no difference was observed between delgocitinib and cream vehicle in the proportion of patients who presented adverse events (AEs) and serious AEs. Rates of AEs, AEs probably or possibly related to study drug or AEs leading to discontinuation of study drug were numerically higher with cream vehicle compared to delgocitinib from baseline to trial completion (delgocitinib 45.2% vs. cream vehicle 50.6%, 3.7% vs. 8.0% and 0.6% vs. 3.7%, respectively). The most common AEs (≥5% in any treatment group) during the study were COVID-19 infections and nasopharyngitis and rates were comparable between the treatment arms.¹

“There is a high unmet need for a topical treatment specifically tailored for moderate-to-severe CHE for patients living with this hard-to-treat disease”, said Robert Bissonnette, MD, FRCPC, President of Innovaderm Research in Quebec, Canada, and the International Coordinating Investigator (ICI) of DELTA 1. “These positive results, which show significant improvements in primary and all key secondary endpoints, demonstrate that delgocitinib cream, if approved, can be a much-needed topical treatment option for patients living with moderate-to-severe CHE.”

Subjects who completed 16 weeks of treatment in trials DELTA 1 or DELTA 2 were offered to roll-over to the DELTA 3 extension trial evaluate the long-term safety and efficacy of an as-needed treatment with twice-daily applications of delgocitinib cream.⁴

“I’m personally very excited about LEO Pharma’s broad data representation at this year’s AAD, which demonstrates our strong commitment to advancing medical dermatology,” said Christophe Bourdon, Chief Executive Officer, LEO Pharma. “CHE is a debilitating, difficult-to-treat disease that negatively impacts patient quality of life, physical functioning, and ability to work. We are incredibly excited to share the positive results of this trial, which demonstrates the potential that delgocitinib cream has as a first-in-class innovative topical treatment.”

For more information on the DELTA 1 trial (NCT04871711) go to clinicaltrials.gov.

About the DELTA 1, 2 and 3 Trials

The primary objective for the randomized, double-blind, vehicle-controlled, multi-center phase 3 clinical trials (DELTA 1 and DELTA 2) is to evaluate the efficacy of twice-daily applications of delgocitinib cream compared with cream vehicle in the treatment of adults with moderate-to-severe CHE.^2,3

The primary endpoint of the trials is the Investigator’s Global Assessment for chronic hand eczema treatment success (IGA-CHE TS) at Week 16. Treatment success is defined as an IGA-CHE score of 0 (clear) or 1 (almost clear, with little or no disease left) with at least a two-step improvement from baseline. Additional IGA-CHE scores include 2 (mild), 3 (moderate), and 4 (severe).

Key secondary endpoints at Week 16 include 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 defines the key safety endpoint of the trials.

Subjects who completed 16 weeks of treatment with delgocitinib cream or cream vehicle twice daily in trials DELTA 1 or DELTA 2 were offered to roll-over to the DELTA 3 extension trial. The purpose of this extension trial is to evaluate the long-term effects of delgocitinib.⁴

About Chronic Hand Eczema

Chronic Hand Eczema (CHE) is defined as hand eczema (HE) that lasts for more than three months or relapses twice or more within a year.^5,6 HE is the most common skin disorder of the hands⁷ with a one-year prevalence rate of approximately 9%.⁸ In a substantial number of patients, HE can develop into a chronic condition.⁷ CHE is a fluctuating disorder characterized by itch and pain, and patients may experience signs such as erythema, scaling, lichenification, hyperkeratosis, vesicles, edema, and fissures on hands and wrists.⁹

About delgocitinib

Delgocitinib is a first-in-class investigational topical pan-Janus kinase (JAK)-inhibitor that inhibits activation of the JAK-STAT pathway, which plays a key role in the immune system in driving the pathophysiology of chronic inflammatory skin diseases.^10,11 LEO Pharma is currently developing delgocitinib in a cream formulation for the treatment of moderate to severe chronic hand eczema (CHE) in adults.

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 for topical use in dermatological indications worldwide, excluding Japan, where JT retains rights.

About LEO Pharma

LEO Pharma is a global company dedicated to advancing the standard of care for the benefit of people with skin conditions, their families and society. Founded in 1908 and majority owned by the LEO Foundation, LEO Pharma has devoted decades of research and development to advance the science of dermatology, and today, the company offers a wide range of therapies for all disease severities. LEO Pharma is headquartered in Denmark with a global team of 4,700 people, serving millions of patients across the world. In 2022, the company generated net sales of DKK 10.6 billion.

References:

1. Bissonnette R, Warren RB, Stingeni L, et al. Efficacy and safety of delgocitinib cream in adults with moderate-to-severe chronic hand eczema: results of the Phase 3 DELTA 1 trial. Presented at American Academy of Dermatology (AAD) 2023 Annual Meeting, New Orleans, La., March 17-21, 2023.
2. ClinicalTrials.gov. National Library of Medicine (U.S.). Efficacy and Safety of Delgocitinib Cream in Adults With Moderate to Severe Chronic Hand Eczema (DELTA 1). Identifier: NCT04871711. https://clinicaltrials.gov/ct2/show/NCT04872101.
3. ClinicalTrials.gov. National Library of Medicine (U.S.). Efficacy and Safety of Delgocitinib Cream in Adults With Moderate to Severe Chronic Hand Eczema (DELTA 2). Identifier: NCT04872101. https://clinicaltrials.gov/ct2/show/NCT04872101.
4. ClinicalTrials.gov. National Library of Medicine (U.S.). Open-label Multi-site Extension Trial in Subjects Who Completed the DELTA 1 or DELTA 2 Trials (DELTA3). Identifier: NCT04949841 https://clinicaltrials.gov/ct2/show/NCT04949841.
5. Lynde C, Guenther L, Diepgen TL, et al. Canadian hand dermatitis management guidelines. J Cutan Med Surg. 2010;14(6):267-284.
6. Diepgen TL, Andersen KE, Chosidow O, et al. Guidelines for diagnosis, prevention and treatment of hand eczema. J Dtsch Dermatol Ges. 2015;13(1):e1-e22.
7. Bissonnette R, Diepgen TL, Elsner P, et al. Redefining treatment options in chronic hand eczema (CHE). J Eur Acad Dermatol Venereol. 2010;24 Suppl 3:1-20.
8. Thyssen JP, Johansen JD, Linneberg A, Menné T. The epidemiology of hand eczema in the general population--prevalence and main findings. Contact Dermatitis. 2010;62(2):75-87.
9. Thyssen JP, Schuttelaar MLA, Alfonso JH, et al. Guidelines for diagnosis, prevention, and treatment of hand eczema. Contact Dermatitis. 2022;86(5):357-378.
10. Damsky W, King BA. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol. 2017;76(4):736-744. doi:10.1016/j.jaad.2016.12.005.
11. T Virtanen A, Haikarainen T, Raivola J, Silvennoinen O. Selective JAKinibs: Prospects in Inflammatory and Autoimmune Diseases. BioDrugs. 2019;33(1):15-32.

MAT-64451 March 2023