Delgocitinib

LEO Pharma’s Anzupgo (delgocitinib) cream has been approved by the European Commission (EC) to treat adults with moderate-to-severe chronic hand eczema (CHE) for whom topical corticosteroids are inadequate or inappropriate. The pan-Janus kinase (JAK) inhibitor is now the first topical treatment specifically indicated for this patient population in the EU. CHE, an inflammatory skin disease, is defined as hand eczema that lasts for more than three months or relapses at least twice within a year. In addition to physical symptoms such as fluctuating itch and pain, CHE has been shown to cause psychological and functional burdens that impact quality of life, with approximately 70% of patients who live with severe cases of the condition reporting problems performing everyday activities. LEO’s Anzupgo is designed to inhibit the activation of the JAK-STAT signalling pathway, which plays a key role in CHE. The approval follows a recent recommendation from the European Medicines Agency’s human medicines committee and was supported by positive results from the late-stage DELTA 1 and DELTA 2 trials, which compared the safety and efficacy of the therapy to vehicle cream. The primary endpoint, Investigator’s Global Assessment for chronic hand eczema treatment success at week 16, was met in both studies and all secondary endpoints were achieved, including a reduction in itch and pain scores of at least four points, as measured by the Hand Eczema Symptom Diary from baseline to week 16. Data from the 36-week DELTA 3 open-label extension trial, which demonstrated a consistent safety profile and sustained treatment success, also informed the regulator’s decision. LEO’s chief executive officer, Christophe Bourdon, said: “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.” The company has also announced that its new drug application for delgocitinib cream in CHE has been accepted for filing by the US Food and Drug Administration, with the regulatory review process expected to conclude in the second half of 2025. Bourdon said: “Alongside our ongoing efforts in Europe, we will approach our work to provide delgocitinib cream in the US with the same determination and dedication.”

BALLERUP, Denmark--( BUSINESS WIRE )-- NOT FOR UK USE – NOT INTENDED FOR UK MEDIA LEO Pharma A/S, a global leader in medical dermatology, today presented late-breaking data on the DELTA FORCE trial and shared six additional abstracts as part of the scientific program for Anzupgo ® (delgocitinib) cream as a potential treatment for adult patients with moderate to severe chronic hand eczema (CHE), for whom topical corticosteroids are inadequate or inappropriate. The findings for delgocitinib cream have been delivered as part of one of LEO Pharma’s most extensive scientific programs to date at the 33 rd European Academy of Dermatology and Venereology (EADV) Congress in Amsterdam. 1-7 The 12-week head-to-head DELTA FORCE phase 3 clinical trial (N=513) evaluated the efficacy and safety of delgocitinib cream compared with oral alitretinoin capsules. 8 Alongside delgocitinib cream, alitretinoin is the only other treatment currently approved in the European Union to specifically treat severe CHE in patients who do not respond to topical corticosteroids. 9-11 Delgocitinib cream achieved the primary outcome measure of the trial, with a significantly greater least squares (LS) mean decrease in Hand Eczema Severity Index (HECSI) score from baseline to Week 12 (67.6) compared to alitretinoin (51.5, P<0.001). 1 The topical treatment also demonstrated superiority to alitretinoin across all key secondary outcome measures. This included a significantly greater proportion of delgocitinib cream patients achieving Investigator’s Global Assessment (IGA)-CHE treatment success (TS) after 12 weeks (27.2%) compared to those receiving alitretinoin (16.6%; P=0.004). Patients who received delgocitinib cream also experienced fewer treatment-emergent adverse events (AEs) (49.4%) compared to those receiving alitretinoin capsules (76.1%). 1 “ The completion of the DELTA FORCE study marks a significant milestone in our understanding of moderate to severe chronic hand eczema treatment,” said Kreesten Meldgaard Madsen, Chief Development Officer, LEO Pharma. “ With the full results now available, we have gained a new understanding of how topical treatment with delgocitinib cream compares to alitretinoin. This groundbreaking news forms just one part of the vast amount of data LEO Pharma is presenting at EADV 2024, all of which work to address the critical unmet needs of dermatology patients.” “ Alongside the results of DELTA FORCE, an extensive body of work, encompassing clinical trial data, real-world findings from both clinicians and patients, and a detailed biopsy analysis provides a multifaceted view of CHE and its treatment landscape,” said Alexander Egeberg, Head of Global Medical Affairs, LEO Pharma. “ T his data not only enhances our knowledge of CHE management but also potentially paves the way for a new topical option in clinicians’ therapeutic arsenal.” Additional novel investigational delgocitinib cream research: A post hoc analysis of 638 patients treated with delgocitinib cream across the DELTA 1, 2, and 3 clinical trials investigated the drug’s efficacy across 5 subtypes of CHE after 16 weeks of treatment. The following 5 CHE subtypes were built into the analysis: irritant contact dermatitis, vesicular hand eczema, allergic contact dermatitis, atopic hand eczema and hyperkeratotic hand eczema. 2 Data from the large multi-national RWEAL study (N=1939) found that CHE patients often present with signs, symptoms and multiple aetiological subtypes. 3 This was presented at EADV alongside other RWEAL data that showed a significant proportion of patients had no other dermatological or atopic condition besides CHE, with fewer than half (43.8%) ever having atopic dermatitis. 4 Together, these data show that CHE is a distinct, complex condition with a significant unmet need. 3,4 Real-world findings from the population-based CHECK study found that the health-related quality of life of CHE patients is increasingly impaired at each step of the treatment ladder, with a mean Dermatology Life Quality Index (DLQI) score of 5.9 for participants reporting treatment with injectables, 6.6 for topical corticosteroids, and 3.0 for those not currently on treatment. 5 Qualitative analysis of DELTA 1 patient exit interviews (N=27) confirms the sizable real-world impact of CHE disease burden. An impact on daily living was reported by 96.3% of patients and 88.9% reported an impact on emotional wellbeing due to their CHE. 6 Another presentation examined the biopsy samples analysis of 41 patients and showed severe CHE was associated with a strong dysregulation of genes in various pathways involved in skin inflammation and barrier function. Treatment with delgocitinib cream appeared to normalize the inflammatory processes and restore skin barrier integrity by inhibiting JAK signalling pathways. 7 In addition to the data submitted, LEO Pharma will also present a symposium on Friday the 27 th of September, titled “ Chronic Hand Eczema Breaking the Silent Conversation”. The session will explore the role of patient voices when managing CHE. *ENDS* About the DELTA FORCE Trial DELTA FORCE was a 24-week, randomized, assessor-blinded, active-controlled, parallel-group, phase 3, two-arm trial to compare the efficacy and safety of delgocitinib cream twice-daily with oral alitretinoin capsules once-daily in adult participants with severe chronic hand eczema. 8 The primary endpoint of the trial was the change in Hand Eczema Severity Index (HECSI) score from baseline to Week 12. Participants assigned to receive delgocitinib cream applied the drug to the skin twice a day for 16 weeks. Participants assigned to receive alitretinoin capsules took the drug orally once a day for 12 weeks. All participants were permitted to continue for up to 24 weeks if the doctor considered that they were benefiting from the treatment. 8 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 compared with cream vehicle in the treatment of adults with moderate to severe CHE. 12-14 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). 12-14 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. 12-14 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. 15 About the RWEAL study The RWEAL (Real-World trEatment & mAnagement of chronic hand eczema in cLinical practice) study is a medical chart review which involved (n=292) physicians from Canada, Germany, France, Italy, Spain, and the UK. Patients ≥18 years of age with moderate to severe CHE treated with TCS in the past 12 months, or with TCS contraindication, were randomly selected from physician’s overall caseload in the preceding 12 months. Data on treatments used in the 12 months prior to the last visit was collected and analyzed descriptively. 3,4 The objective of the RWEAL study was to investigate treatment patterns in patients with moderate to severe CHE over 12 months, focusing on topical corticosteroid (TCS) therapy. 3,4 About the CHECK study CHECK (Chronic Hand Eczema epidemiology, Care, and Knowledge of real-life burden) is a population-based study which recruited (n=60,131) participants in six countries including Canada, Germany, France, Italy, Spain, and the UK aged 18-69 via online panels. Participants were representative of the general population regarding sex, age, region, employment status, urban/rural setting, and, for the UK, ethnicity. 5,16 The objective of the CHECK study was to investigate and analyze self-reported disease severity, symptoms, and treatments in CHE. Furthermore, the study estimated the prevalence of CHE among adults aged 18 to 69 in the general population and described the prevalence according to key socio-demographic characteristics. The association and impact of CHE on exposures and occupation or household/leisure activities were also investigated. 5,16 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. 9,17 CHE is one the most common skin disorder of the hands with a prevalence rate of approximately 4.7%. 16 In a substantial number of patients, HE can develop into a chronic condition. 18 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. 10 CHE has been shown to cause psychological and functional burdens that impact patient quality of life, 19 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. 20 Furthermore, careers and earning potential have also been shown to be impacted by the burden of living with CHE. 21 About Anzupgo ® (delgocitinib) cream Anzupgo ® (delgocitinib) cream 20 mg/g 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. 22 The pathophysiology is characterized by skin barrier dysfunction, inflammation of the skin, and alterations of the skin microbiome. 23 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 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 Giménez-Arnau AM, Pinter A, Sondermann W et al. DELTA FORCE trial: 24-week Phase 3 trial comparing the efficacy and safety of topical delgocitinib cream with oral alitretinoin capsules in adults with severe CHE. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Late Breaking News Session. D1T01.1. Bisonnette R, Schliemann S, Gooderham M, et al. Treatment response of delgocitinib cream according to CHE subtypes in adults with moderate to severe CHE: results from the Phase 3 DELTA 1, DELTA 2, and DELTA 3 trials. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation. FC07.04. Fargnoli MN, Molin S, Bewley A, et al. The multifactorial and heterogenous nature of CHE in clinical practice: Results from the RWEAL study. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation. P0608. Giménez-Arnau AM, Bewley A, Molin S, et al. Patient characteristics and comorbidities in moderate-to-severe CHE: Results from the RWEAL study. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation. P2559. Bewley A, Molin S, Crepy MN, et al. Health-related quality of life in people with CHE - Findings from the multi-national CHECK study. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. E-poster Presentation. P3443. Mohandas P, Devani AR, Baranowski K, et al. Clinical trial exit interviews in patients with moderate to severe CHE: perspectives on disease burden and its impact on quality of life from participants in the phase 3 DELTA 1 trial. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. E-poster Presentation. P0532. Worm M, Jiang L, Litman T, et al. Topical pan-JAK inhibition with delgocitinib restores the molecular signature of lesional skin in patients with CHE. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation. P0572. ClinicalTrials.gov. National Library of Medicine (U.S.). A 24 Week Trial to Compare the Efficacy and Safety of Delgocitinib Cream 20 mg/g Twice-daily With Alitretinoin Capsules Once-daily in Adult Participants With Severe Chronic Hand Eczema. Identifier: NCT05259722. https://clinicaltrials.gov/study/NCT05259722 . 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. Thyssen JP, Schuttelaar MLA, Alfonso JH, et al. Guidelines for diagnosis, prevention, and treatment of hand eczema. Contact Dermatitis. 2022;86(5):357-378. Anzupgo ® (delgocitinib) cream. Summary of Product Characteristics. LEO Pharma; September 2024. 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/study/NCT04871711 . 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 . 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; published online July 18. https://doi.org/10.1016/S0140-6736(24)01027-4 . 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 . 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 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. 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. 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. 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. 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. 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. Lee GR, Maarouf M, Hendricks AK, Lee DE, Shi VY. Current and emerging therapies for hand eczema. Dermatol Ther. 2019;32(3):e12840. MAT-76323 September 2024