FDA Accepts LEO Pharma’s Filing of Delgocitinib Cream New Drug Application for the Treatment of Chronic Hand Eczema

• LEO Pharma is expanding upon its ambitions in the United States (U.S.) as the FDA has accepted for filing the company’s New Drug Application (NDA) for delgocitinib cream, an investigational innovative topical treatment for Chronic Hand Eczema (CHE).

• The application has been accepted for filing and, if approved, delgocitinib cream would become the first treatment in the U.S. specifically indicated for adults with moderate to severe CHE.
• CHE is a condition with a high unmet need that affects approximately 4.7% of the population globally.¹

MADISON, New Jersey--(BUSINESS WIRE)--NOT FOR UK USE – NOT INTENDED FOR UK MEDIA

LEO Pharma Inc. announced today that the Food and Drug Administration (FDA) has accepted for filing a New Drug Application (NDA) for delgocitinib cream 20 mg/g (2%) for the treatment of adults with moderate to severe Chronic Hand Eczema (CHE), who have had an inadequate response to, or for whom topical corticosteroids are not advisable.

This marks an important next step on LEO Pharma’s path to providing delgocitinib cream to adults living with moderate to severe CHE, a condition for which there are currently no FDA approved treatments. This news is the latest in a series of regulatory milestones globally. Today LEO Pharma also announced the European Commission (EC) approval for delgocitinib cream in the European Union (EU).²

“Our hands are integral to every practical aspect of our lives, from our ability to work, to connecting with loved ones. Today, I am incredibly proud that LEO Pharma is taking a step towards addressing the long-standing unmet need in CHE for those in the U.S.” said Christophe Bourdon, CEO of LEO Pharma A/S. “This news is testament to our dedication to making a fundamental difference for those who need us most in medical dermatology. Alongside our ongoing efforts in Europe, we will approach our work to provide delgocitinib cream in the U.S. with the same determination and dedication.”

The regulatory submission for delgocitinib cream 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 delgocitinib cream compared to cream vehicle.^3-5 Both trials met their primary and all secondary endpoints.^6,7

Subjects who completed the 16-week DELTA 1 or DELTA 2 trials were extended the offer to enroll in the 36-week DELTA 3 open-label extension trial.^8,9

Delgocitinib cream is an investigational topical pan-JAK inhibitor for the treatment of moderate to severe CHE in adults. It inhibits the activation of JAK-STAT signaling, which plays a key role in the pathogenesis of CHE.¹⁰

“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, 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.”

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.¹¹ The condition can have a high psychological, social, and occupational burden.^12-14

“Over the last few years, we have significantly strengthened our presence in the U.S. through a determined effort to support dermatologists in making a difference for those living with skin conditions,” said Brian Hilberdink, EVP and President, Region North America, LEO Pharma. “With today’s announcement, we reinforce our commitment to addressing the high unmet need of U.S. patients living with CHE, a condition that can significantly impact quality of life, including an impact to mental wellbeing. The announcement of the filing of the NDA for delgocitinib cream is a validation of our mission to advance the standard of care, and we are committed to working closely with the FDA in the coming months during its review.”

The regulatory review process is expected to conclude in the second half of 2025.

Notes to editors

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 delgocitinib cream 20 mg/g (2%) compared with cream vehicle in the treatment of adults with moderate to severe CHE.^3-5

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).^3-5

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.^3-5

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 36-week DELTA 3 Open-label, Multi-site Extension trial. The purpose of this extension trial was to evaluate the long-term safety of delgocitinib.⁸

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.^15,16 CHE is one of the most common skin disorders of the hands with a prevalence rate of approximately 4.7%.¹ In a substantial number of patients, HE can develop into a chronic condition.¹⁷ 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.¹²

CHE has been shown to cause psychological and functional burdens that impact patient quality of life,¹³ 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.¹⁹ Furthermore, careers and earning potential have also been shown to be impacted by the burden of living with CHE.²⁰

About Delgocitinib Cream

Delgocitinib Cream, which is marketed in the EU under the tradename Anzupgo® (delgocitinib) Cream, is an investigational topical pan-Janus kinase (JAK) inhibitor for moderate to severe CHE. It inhibits the activation of JAK-STAT signaling, which plays a key role in the pathogenesis of CHE.¹¹ The pathophysiology is characterized by skin barrier dysfunction, inflammation of the skin, and alterations of the skin microbiome.¹¹ LEO Pharma is currently developing delgocitinib cream formulation for the treatment of moderate to severe Chronic Hand Eczema (CHE) in adults, which is currently not approved by any health authority. 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 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.

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References

1. 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
2. Delgocitinib SmPC; September 2024
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 1). Identifier: NCT04871711. https://clinicaltrials.gov/ct2/show/NCT04872101.
4. 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.
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6. 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.
7. 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.
8. 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.
9. Gooderham M, et al. Long-term safety and efficacy of delgocitinib cream for up to 36 weeks in adults with Chronic Hand Eczema: results of the Phase 3 open-label extension DELTA-3 trial. Presented at the 2024 American Academy of Dermatology Annual Meeting; March 8-12 2024; San Diego, CAx
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MAT-76480 September 2024