European Commission Approves LEO Pharma’s Anzupgo® (delgocitinib) Cream for Adults with Moderate to Severe Chronic Hand Eczema (CHE)

• Anzupgo^® is the first topical treatment to be specifically indicated for adult patients living with moderate to severe CHE across the European Union (EU) for whom topical corticosteroids are inadequate or inappropriate.
• The approval follows the recent positive opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) and is based on results from the DELTA phase 3 program.^1-5

BALLERUP, Denmark--(BUSINESS WIRE)--NOT FOR UK USE – NOT INTENDED FOR UK MEDIA

LEO Pharma A/S, a global leader in medical dermatology, today announced that the European Commission (EC) has granted marketing authorization for Anzupgo^® (delgocitinib) cream for the treatment of adult patients with moderate to severe chronic hand eczema (CHE) for whom topical corticosteroids are inadequate or inappropriate.¹

The EC approval is valid in all European Union Member States, Iceland, Norway, and Liechtenstein.¹ This news is the latest in a series of regulatory milestones globally. Today LEO Pharma also announced that the FDA has accepted for filing LEO Pharma’s New Drug Application (NDA) for delgocitinib cream in the United States.

“We are dedicated to advancing the standard of care for those living with skin conditions, and this long-awaited milestone for Anzupgo demonstrates our purpose in practice,” said Christophe Bourdon, Chief Executive Officer, LEO Pharma. “This approval provides a new treatment option for patients, and we look forward to coordinating the next steps required to provide Anzupgo to those patients who need it.”

Anzupgo is a topical pan-JAK inhibitor for the treatment of moderate to severe CHE. It inhibits the activation of JAK-STAT signaling, which plays a key role in the pathogenesis of CHE.⁶ Currently, there are no other topical treatments specifically approved for adults with moderate to severe CHE for whom topical corticosteroids are inadequate or inappropriate.

“This approval is the culmination of years of focus and effort, driven every day by the goal to support this patient population,” said Kreesten Meldgaard Madsen, Chief Development Officer, LEO Pharma. “The new treatment option aims to support the management of this debilitating condition, given the limited treatment options for CHE currently approved across Europe”.

CHE is a heterogeneous, fluctuating, inflammatory skin disease with key symptoms of itch and pain. Its pathophysiology is characterized by skin barrier dysfunction, skin inflammation, and skin microbiome alterations.⁷ The condition can have a high psychological, social, and occupational burden.^8-10

The approval for Anzupgo is based on results from the phase 3 program, which includes the DELTA 1 and DELTA 2 clinical trials that evaluated the safety and efficacy of Anzupgo compared to cream vehicle.^2-4 Both trials met their primary and all secondary endpoints.^11,12 Subjects who completed the 16-week DELTA 1 or DELTA 2 trials were immediately offered to enroll in the 36-week DELTA 3 open-label extension trial.⁵

About Anzupgo^® (delgocitinib) cream

Anzupgo^® (delgocitinib) cream is a topical pan-Janus kinase (JAK) inhibitor for the treatment of moderate to severe CHE. It inhibits the activation of JAK-STAT signaling, which plays a key role in the pathogenesis of CHE.⁶ The pathophysiology is characterized by skin barrier dysfunction, inflammation of the skin, and alterations of the skin microbiome.⁷ Anzupgo is currently approved in the European Union for the treatment of moderate to severe chronic hand eczema (CHE) in adults for whom topical corticosteroids are inadequate or inappropriate. 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 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) was to evaluate the efficacy of twice-daily applications of Anzupgo compared with cream vehicle in the treatment of adults with moderate to severe CHE.^2-4

The primary endpoint of the trials was the Investigator’s Global Assessment for chronic hand eczema treatment success (IGA-CHE TS) at Week 16. Treatment success was defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with at least a two-step improvement from baseline. Additional IGA-CHE scores included 2 (mild), 3 (moderate), and 4 (severe).^2-4

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.^2-4

Subjects who completed 16 weeks of treatment with Anzupgo or cream vehicle twice daily in trials DELTA 1 or DELTA 2 were offered to roll-over to the DELTA 3 Open-label, Multi-site Extension trial. The purpose of this extension trial was to evaluate the long-term safety of Anzupgo.⁵

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.^13,14 HE is the most common skin disorder of the hands¹⁵ with a prevalence rate of approximately 4.7%.¹⁶ In a substantial number of patients, HE can develop into a chronic condition.¹⁵ 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.⁸

CHE has been shown to cause psychological and functional burdens that impact patient quality of life,⁹ with approximately 70% of individuals who live with severe CHE admitting to problems in performing everyday activities, and suffering disruption in their daily life due to the condition.¹⁷ Furthermore, careers and earning potential have also been shown to be impacted by the burden of living with CHE.¹⁸

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 4,200 people, serving millions of patients across the world. In 2023, the company generated net sales of DKK 11.4 billion.

References

1. Anzupgo^® (delgocitinib) cream. Summary of Product Characteristics. LEO Pharma; September 2024.
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. Bissonnette R, Warren RB, Pinter A, et al. 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;404(10451):461-473. doi:10.1016/S0140-6736(24)01027-4.
5. 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.
6. Dubin C, Del Duca E, Guttman-Yassky E. Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges. Ther Clin Risk Manag. 2020;16:1319-1332. Erratum in: Ther Clin Risk Manag. 2021 Mar 18;17:233.
7. Lee GR, Maarouf M, Hendricks AK, Lee DE, Shi VY. Current and emerging therapies for hand eczema. Dermatol Ther. 2019;32(3):e12840.
8. Thyssen JP, Schuttelaar MLA, Alfonso JH, et al. Guidelines for diagnosis, prevention, and treatment of hand eczema. Contact Dermatitis. 2022;86(5):357-378.
9. Grant L, Seiding Larsen L, Burrows K, et al. Development of a Conceptual Model of Chronic Hand Eczema (CHE) Based on Qualitative Interviews with Patients and Expert Dermatologists. Adv Ther. 2020;37(2):692-706.
10. Thyssen JP, Silverberg JI, Guttman-Yassky E. Chronic hand eczema understanding has ramifications on clinical management. J Eur Acad Dermatol Venereol. 2020;34(8):e429-e430.
11. Schliemann S, et al. Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema: results of the Phase 3 DELTA 2 trial. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2023. Berlin, Germany. 11– 14 October. Poster Presentation #P0395.
12. Bissonnette R, 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 the European Academy of Dermatology and Venereology (EADV) Congress 2023. Berlin, Germany. 11– 14 October. Poster Presentation #P0369.
13. Lynde C, Guenther L, Diepgen TL, et al. Canadian hand dermatitis management guidelines. J Cutan Med Surg. 2010;14(6):267-284. Erratum in: J Cutan Med Surg. 2011 Nov-Dec;15(6):360
14. Diepgen TL, et al. Guidelines for diagnosis, prevention and treatment of hand eczema. J Dtsch Dermatol Ges. 2015 Jan;13(1):e1–22.
15. 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.
16. Apfelbacher C, Bewley A, Molin S, et al. Prevalence of Chronic Hand Eczema in adults: A cross-sectional multi-national study of 60,000 respondents in the general population. Presented at the 2024 European Society of Contact Dermatitis (ESCD) congress; September 04-07 2024; Dresden, Germany. Poster presentation #3
17. Cortesi PA, Scalone L, Belisari A, et al. Cost and quality of life in patients with severe chronic hand eczema refractory to standard therapy with topical potent corticosteroids. Contact Dermatitis. 2014;70(3):158-168.
18. Voorberg AN, Loman L, Schuttelaar MLA. Prevalence and Severity of Hand Eczema in the Dutch General Population: A Cross-sectional, Questionnaire Study within the Lifelines Cohort Study. Acta Derm Venereol. 2022;102:adv00626.

MAT-76332 September 2024