RARα agonists(Retinoic acid receptor alpha agonists), RARβ2 agonists(Retinoic acid receptor beta agonists), RARγ agonists(Retinoic acid receptor gamma agonists)

Therapeutic Areas

NeoplasmsImmune System DiseasesInfectious Diseases+ [2]

Active Indication

AIDS-related Kaposi Sarcoma

Inactive Indication

Acute Promyelocytic LeukemiaBreast CancerBronchial Diseases+ [8]

Originator Organization

Eisai Co., Ltd.

Active Organization

Concordia Pharmaceuticals, Inc.

Inactive Organization

Ligand Pharmaceuticals, Inc.Eisai GmbH

Drug Highest PhaseApproved

First Approval Date

US (02 Feb 1999),

AIDS-related Kaposi Sarcoma

RegulationOrphan Drug (US)

Structure

Molecular FormulaC20H28O2

InChIKeySHGAZHPCJJPHSC-ZVCIMWCZSA-N

CAS Registry5300-03-8

Clinical Trials associated with Alitretinoin

NCT05384821 / RecruitingPhase 1/2IIT

Phase 1-2 Trial Evaluating Metronomic Chemotherapy in Patients With a Relapsed or Refractory Wilms Tumor

This is a multicenter, interventional, non-randomized study among patients with a relapsed or refractory Wilms tumor. The study will aim to assess efficacy of metronomic chemotherapy, in terms of disease control after two cycles of metronomic chemotherapy.

Start Date14 Sep 2022

Sponsor / Collaborator

Centre Oscar Lambret

NCT05077813 / Unknown statusPhase 2IIT

Utilizing the Crosstalk Among Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D as a Potent Quadrate Therapy for Treating Patients With Multidrug-resistant TB and Patient With Both Multidrug-resistant TB and COVID-19

Utilizing the Crosstalk Among Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D as a Potent Quadrate Therapy for treating patients with Multidrug-resistant TB and patient with both Multidrug-resistant TB and COVID-19 . A double-edged sword Clinical Study
I)Part of Tuberculosis
Tuberculosis (TB) is a major infectious disease killer globally. It affected 10 million and killed 1.4 million people in 2019 alone. The predicted impact of the COVID-19 pandemic is an additional 190,000 TB deaths in 2020, and it is expected in the next 5 y that there will be up to a 20% increase in the global TB disease burden , stressing the critical need for new safe and effective drugs against Mycobacterium tuberculosis (Mtb). In addition, controlling multidrug-resistant TB (MDR-TB) presents a huge public health challenge . New drug discovery could require several years with no guarantee but repurposing established may be useful to treat patients with tuberculosis . Here we demonstrate that we could utilize the crosstalk among Chicoric Acid, 13-Cis Retinoic Acid, Minocycline , and vitamin D as a novel quadrate therapy against TB.Drug-resistant tuberculosis represents a global emergency, requiring new drugs. Recently Minocycline was found to be highly potent in laboratory strains of Mycobacterium TB, and 30 drug-sensitive and multidrug/extensively drug-resistant clinical strains were susceptible to clinically attainable dosages. The lung concentration-time profiles of a 7 mg/kg/day human-equivalent minocycline dosage yielded bacterial kill rates comparable to first-line antituberculosis drugs. Extracellular bacilli were destroyed directly by minocycline. Minocycline also killed intracellular bacilli indirectly through granzyme A-driven apoptosis. Furthermore, minocycline showed dose-dependent antiinflammatory effect, suggesting that it may protect tuberculosis patients against immunopathology. A study showed that M. tuberculosis induced the expression of indoleamine 2,3-dioxygenase (IDO), an enzyme involved in tryptophan catabolism, in macrophages and in the lungs of animals (mice and macaque) with active disease. In a macaque model of inhalation TB, suppression of IDO activity reduced bacterial burden, pathology, and clinical signs of TB disease, leading to increased host survival. This increased protection was accompanied by increased lung T cell proliferation, induction of inducible bronchus-associated lymphoid tissue and correlates of bacterial killing . A recent study showed that Minocycline-induced significantly inhibition of IDO expression. But Minocycline-induced inhibition of IDO expression is retinoid-dependent. The combined treatment with minocycline and retinol, however, resulted in a striking, statistically significant decrease in IDO. Co-treatment with minocycline and retinol again resulted in decreased TNF-α and IL-6 levels. A study showed that IL-6 inhibits IFN-γ induced autophagy in Mycobacterium (TB) H37Rv infected macrophages. As well as neutralization of endogenous IL-6 by anti-IL-6 antibody significantly enhances the IFN-γ mediated killing of the intracellular bacteria. Minocycline's anti-inflammatory effects are mediated through RAR signaling. Therefore, The combined treatment with minocycline and retinol is expected to effectively inhibit (TB) and its inflammatory complication, Fortunately, Retinoic Acid significantly inhibits the in vivo growth of M. tuberculosis and the development of tuberculosis. In addition to, 13-Cis RA and Chicoric Acid ( CA ) enhanced the cell surface expression of HLA-DR and CD14 molecules on U937 macrophages and prevented the growth of Mtb within macrophages. Moreover, 13-cis RA and CA, have increased NO generation compared to untreated control macrophages, significantly . Both drugs have a significant inhibitory effect on Mtb growth but CA at the highest concentration was more potent than 13-cis RA . Therefore we will use retinoic acid to induce the effect of Minocycline as well as its ability to inhibit tuberculosis in combination with CA .Recent data showed that Vitamin D support innate immune responses to Mycobacterium TB and Low vitamin D levels were associated with a 5-fold increased risk for progression to tuberculosis. Deficiency of vitamin D has long been implicated in activation of (TB) . Serum vitamin D in TB patients are lower than in healthy controls . Vitamin D has been found to speed up the clearance of (TB) bacteria from the lungs of people with multi-drug resistant TB, according to a study of 1,850 patients. It was showed that Vitamin D receptor (VDR) must form a heterodimer complex with retinoid X receptor (RXR) to regulate gene transcription. Retinol plays a crucial role in lung development and signaling the vitamin D pathway. 9-cis-retinoic acid, an active vitamin A metabolite and the ligand of RXR, assists VDR signaling and suppresses the degradation of circulating vitamin D.

Start Date01 Dec 2021

Sponsor / Collaborator

Kafrelsheikh University

KCT0006687 / Not yet recruitingPhase 4IIT

A multicenter, open-label, single-arm, investigator-initiated clinical trial to evaluate the efficacy and safety of alitretinoin in patients with chronic hand eczema in real patient encounter

Start Date25 Oct 2021

Sponsor / Collaborator-

100 Clinical Results associated with Alitretinoin

100 Translational Medicine associated with Alitretinoin

100 Patents (Medical) associated with Alitretinoin

2,479

Literatures (Medical) associated with Alitretinoin

26 Sep 2024·Journal of Medicinal Chemistry

Tuning RXR Modulators for PGC1α Recruitment

Article

Author: Bitić, Anesa ; Pabel, Jörg ; Schwarzenbach, Roman ; Merk, Daniel ; Nawa, Felix ; Marschner, Julian A. ; Heering, Jan ; Sai, Minh ; Wolff, Sina ; Vietor, Jan ; Ildefeld, Niklas ; Wein, Thomas

The molecular activation mechanism of the nuclear retinoid X receptors (RXRs) crucially involves ligand-induced corepressor release and coactivator recruitment which mediate transcriptional repression or activation. The ability of RXR to bind diverse coactivators suggests that a coregulator-selective modulation by ligands may open an avenue to tissue- or gene-selective RXR activation. Here, we identified strong induction of peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) binding to RXR by a synthetic agonist but not by the endogenous ligand 9-cis retinoic acid. Structure-guided diversification of this lead resulted in a set of three structurally related RXR agonists with different ability to promote PGC1α recruitment in cell-free and cellular context. These results demonstrate that selective modulation of coregulator recruitment to RXR can be achieved with molecular glues and potentially open new therapeutic opportunities by targeting the ligand-induced RXR-PGC1α interaction.

01 Sep 2024·Zeitschrift für Gastroenterologie

Remission of refractory esophageal lichen planus induced by tofacitinib

Article

Author: Schauer, Franziska ; Schmitt-Graeff, Annette ; Decker, Annegrit ; Bieneck, Valentina ; Kreisel, Wolfgang

AbstractAs of now, there exists no established therapy for ELP. Retinoids, which are standard in treating cutaneous LP, do not exhibit positive effects in ELP. While topical glucocorticosteroids often yield favorable responses in esophageal inflammation, some cases prove recalcitrant or refractory. In such instances, various immunosuppressive therapies have been attempted with variable success.This report details a severe case of ELP that showed resistance to prednisolone, acitretin, alitretinoin, adalimumab, tacrolimus, hydroxychloroquine plus mycophenolate mofetil, and cyclophosphamide. The initiation of the JAK inhibitor tofacitinib induced an impressive clinical, endoscopic, and histological remission. This positive response to a JAK inhibitor is discussed in the context of our evolving understanding of the immune-mediated pathogenesis of this disease.

01 Sep 2024·Journal of Food Science

Phytochemical profile, bioactivity, and molecular docking studies of natural edible mushrooms grown in Tokat and Sivas provinces of Turkey

Article

Author: Ozen, Tevfik ; Turkekul, Ibrahim ; Marah, Sarmed ; Bayram, Onur Furkan

AbstractMushrooms have been essential to the human diet because they contain balanced chemical components and some biologically active substances. In this work, we investigated the phenolics, essential oils, metal contents, antioxidant, antibacterial, DNA protective, and enzyme inhibition activities for Clitocybe geotropa, Ramaria aurea, Rhizopogon luteolus (RL), Russula delica (RD), Verpa bohemica, and Marasmius oreades mushrooms. Results exhibited a higher content for citric and succinic acids in all tested kinds. Further, we detected a high content of cis‐9‐oleic acid, linoleate, and cis‐11‐eicosanoate. All mushroom species contain a significant percentage of both Cu and Zn. Moreover, RL and RD recorded the highest phenolic and flavonoid contents. Furthermore, all samples showed standard to good antioxidant activity, and the same is true for the antibacterial and DNA protective activities. Enzyme inhibition activity was generally high and significantly higher against the urease than the thiourea. We applied molecular docking between the highest phenolic molecules with the urease to determine the mushroom extracts’ high inhibition mechanism. In conclusion, all mushroom species revealed a variety in chemical content that is probably related to their multi‐bioactivity.

News (Medical) associated with Alitretinoin

25 Sep 2024

·www.businesswire.com

LEO Pharma Presents Late-Breaking Anzupgo® (delgocitinib) Cream Presentation at EADV 2024 Highlighting Results of Head-to-Head DELTA FORCE Trial in Chronic Hand Eczema (CHE)

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

Clinical ResultPhase 3License out/inDrug Approval

25 Sep 2024

·www.businesswire.com

LEO Pharma Unveils Most Extensive EADV Program To Date with 5 Late Breaking Abstracts and 23 Posters Sharing Clinical and Real-World Data

BALLERUP, Denmark--( BUSINESS WIRE )-- NOT FOR UK USE – NOT INTENDED FOR UK MEDIA LEO Pharma A/S, a global leader in medical dermatology, will present new clinical and real-world data from across its portfolio of products at the upcoming 33 rd European Academy of Dermatology and Venereology (EADV) Congress. The event will be held from the 25 th to the 28 th of September in Amsterdam, Netherlands, where LEO Pharma will present 5 coveted late-breaking presentations in addition to 23 scientific posters for a range of skin conditions, forming the largest collection of data LEO Pharma has ever shared at the EADV congress. 1-28 “ It is extraordinary to witness the breadth and variety of LEO Pharma’s scientific contribution at this year’s EADV Congress. It is a record-breaking presence for us – and we cannot wait to share this ground-breaking data with the medical dermatology community ,” said Christophe Bourdon, CEO of LEO Pharma. The first late-breaking presentation for Anzupgo ® (delgocitinib) cream will provide data from the 24-week DELTA FORCE trial that compared the efficacy and safety of topical delgocitinib cream with oral alitretinoin capsules in adults with severe CHE. 1 An additional late-breaking oral presentation will provide data from the matching-adjusted indirect comparison (MAIC) of the efficacy of delgocitinib and dupilumab in the treatment of moderate to severe atopic hand eczema. 25 The third delgocitinib cream late-breaking presentation will provide information on biomarker and efficacy data from the randomized vehicle-controlled clinical trial with delgocitinib cream in patients with frontal fibrosing alopecia. 26 A late-breaking presentation will also be presented for Adtralza/Adbry, highlighting the interim real-world effectiveness results of tralokinumab in adult patients with head and neck atopic dermatitis after up to 9 months of treatment in the TRACE real world evidence (RWE) study. 27 Finally, a late-breaking presentation for temtokibart will also be presented, comparing clinical and molecular responses in the targeting of IL-22RA1 with temtokibart vs dupilumab in patients with moderate to severe atopic dermatitis. 28 " The 2024 EADV Congress marks a pivotal moment for LEO Pharma as we unveil a wealth of new data," said Kreesten Meldgaard Madsen, Chief Development Officer, LEO Pharma. " Our presentations at EADV showcase our most comprehensive research portfolio to date, underscoring our unwavering commitment to developing innovative dermatological therapies and helping to bring new hope to patients grappling with challenging skin conditions." The company’s full roster at the 2024 EADV Congress, encompassing new research, encore abstracts, and 3 symposiums, 1-28 includes: Anzupgo ® (delgocitinib) cream DELTA FORCE trial: A 24-week head-to-head phase 3 trial comparing the efficacy and safety of topical delgocitinib cream with oral alitretinoin capsules in adults with severe chronic hand eczema Author: Ana Maria Giménez-Arnau Presentation ID: D1T01.1F LB presentation: Wednesday, 25 Sep, 15:30 - 15:45 Location: Auditorium Matching-adjusted indirect comparison of the efficacy of delgocitinib and dupilumab in the treatment of moderate to severe atopic hand eczema Author: David Cohen Presentation ID: D3T01.4B LB presentation: Friday, 27 Sep, 16:15 - 16:30 Location: Auditorium Randomized vehicle-controlled clinical trial with the topical JAK inhibitor delgocitinib in patients with frontal fibrosing alopecia demonstrates biomarker and clinical efficacy Author: Maryanne Makredes Senna Presentation ID: D3T01.4F LB presentation: Friday, 27 Sep, 17:15 - 17:30 Location: Auditorium Treatment response of delgocitinib cream according to Chronic Hand Eczema (CHE) subtypes in adults with moderate to severe CHE: results from the Phase 3 DELTA 1, DELTA 2, and DELTA 3 trials Author: Robert Bissonnette Presentation ID: FC07.04 Oral presentation: Friday, 27 Sep, 14:45 - 14:55 Location: G104-G105 Topical pan-JAK inhibition with delgocitinib restores the molecular signature of lesional skin in patients with Chronic Hand Eczema Author: Sonja Molin Poster ID: P0572 ePoster presentation Health-related quality of life in people with Chronic Hand Eczema - Findings from the multi-national CHECK study Author: Anthony Bewley Poster ID: P3443 ePoster presentation Clinical trial exit interviews in patients with moderate to severe Chronic Hand Eczema: perspectives on disease burden and its impact on quality of life from participants in the phase 3 DELTA 1 trial Author: Padma Mohandas Poster ID: P0532 ePoster presentation Patient characteristics and comorbidities in moderate-to-severe CHE: Results from the RWEAL study Author: Maria Concetta Fargnoli Poster ID: P2559 ePoster presentation The multifactorial and heterogenous nature of Chronic Hand Eczema in clinical practice: Results from the RWEAL study Author: Maria Concetta Fargnoli Poster ID: P0608 ePoster presentation Delgocitinib cream reduces itch and pain in adults with moderate to severe Chronic Hand Eczema: pooled analyses of the Phase 3 DELTA 1 and 2 trials Author: Andrea Bauer Poster ID: P0564 ePoster presentation Efficacy and safety of delgocitinib cream in adults with moderate to severe Chronic Hand Eczema: pooled results of the Phase 3 DELTA 1 and 2 trials Author: Marie Louise Schuttelaar Poster ID: P0569 ePoster presentation Systemic exposure and safety profile of delgocitinib cream in adults with moderate to severe Chronic Hand Eczema in the Phase 3 DELTA 2 trial Author: Melinda Gooderham Poster ID: P0581 ePoster presentation 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 Author: Sonja Molin Poster ID: P0565 ePoster presentation Association and impact of Chronic Hand Eczema on occupational and household/leisure activities– results from the multinational CHECK study Author: Marie Noelle Crepy Poster ID: P1076 ePoster presentation Prevalence of Chronic Hand Eczema in adults: A cross-sectional multi-national study of over 60,000 respondents in the general population Author: Christian Apfelbacher Poster ID: P1901 ePoster presentation Treatment patterns in moderate to severe Chronic Hand Eczema - Results from the multinational RWEAL medical chart review Author: Ana Maria Giménez-Arnau Poster ID: P3568 ePoster presentation Self-reported disease severity and treatment of Chronic Hand Eczema from the CHECK study - A multinational study in six countries Author: Sonja Molin Poster ID: P3526 ePoster presentation Adtralza ® (tralokinumab)/Adbry ® (tralokinumab-ldrm) Real-world effectiveness of tralokinumab in adults with atopic dermatitis: Interim data on improvements in patients with head and neck atopic dermatitis after up to 9 months of treatment in the TRACE study Author: April Armstrong Presentation ID: D3T01.3C LB presentation: Friday, 27 Sep, 14:45 - 15:00 Location: Auditorium Real-world effectiveness of tralokinumab in adults with atopic dermatitis: Interim data on improvements in physician-assessed disease severity after up to 9 months of follow-up in the TRACE study Author: Elena Pezzolo Poster ID: P0689 ePoster presentation Real-world effectiveness of tralokinumab in adults with atopic dermatitis: Interim data on improvements in patient-reported outcomes after up to 9 months of follow-up in the TRACE study Author: Antonio Costanzo Poster ID: P0690 ePoster presentation Long-term safety and efficacy of tralokinumab in patients 65 years or older with moderate-to-severe atopic dermatitis Author: Andrew Blauvelt Poster ID: P0479 ePoster presentation Improvement of the head and neck regions with continuous tralokinumab treatment for up to 4 years in adults with moderate-to-severe atopic dermatitis Author: Raj Chovatiya Poster ID: P0595 ePoster presentation Tralokinumab formulated as a pre-filled pen was efficacious and well-tolerated in adults and adolescents with moderate-to-severe atopic dermatitis Author: Jennifer Soung Poster ID: P0574 ePoster presentation Stability of long-term therapeutic responses to tralokinumab in adults with moderate-to-severe atopic dermatitis Author: Andrew Blauvelt Poster ID: P0596 ePoster presentation Kyntheum ® (brodalumab) Observational study to assess the real-life descriptive effectiveness in patients with moderate to severe plaque psoriasis treated with Brodalumab stratified by patients with BMI>30 and patients with BMI ≤ 30. The BROACTIVE Study. 2 years - results. Author: Juan Escalas Poster ID: P3205 ePoster presentation Long-term management outcome assessment of adult patients with moderate-to-severe plaque psoriasis treated with brodalumab in Greece: The ReSOLVE study. Author: Pantelis Panagakis Poster ID: P3102 ePoster presentation Temtokibart Targeting IL-22RA1 with temtokibart in patients with moderate to severe atopic dermatitis induces fast clinical and molecular responses, distinct from dupilumab Author: Christine Bangert Presentation ID: D2T01.3A LB presentation: Thursday, 26 Sep, 14:15 - 14:30 Location: Auditorium Individual responses to IL-22RA1 inhibition in Asian patients with moderate-to-severe atopic dermatitis in Phase 1 and 2a clinical trials Author: Diamant Thaçi Poster ID: P0691 ePoster presentation In addition to the abstracts and poster presentations, LEO Pharma will also present 3 symposiums at the meeting: A New Era in Atopic Dermatitis Speakers: Prof. Melinda Gooderham, Prof. April Armstrong and Prof. Marjolein de Bruin-Weller 17:45–19:15 CEST on Thursday the 26th of September in Room 7.1, RAI Amsterdam Plaque psoriasis and obesity — a double burden for patients? Speakers: Prof. Dr med. Khusru Asadullah and Dr Matteo Megna 11:15-12:00 CEST on Thursday the 26th of September in Amtrium 1, Hall 4, RAI Amsterdam Chronic Hand Eczema Breaking the Silent Conversation Speakers: Prof. Swen Malte John, Prof. April Armstrong, Dr Marie-Louise Schuttelaar 13:00-14:00 CEST on Friday the 27 th of September in Room 7.3, RAI Amsterdam. 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. 29,30 CHE is one the most common skin disorder of the hands with a prevalence rate of approximately 4.7%. 31 In a substantial number of patients, HE can develop into a chronic condition. 32 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. 33 CHE has been shown to cause psychological and functional burdens that impact patient quality of life, 34 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. 35 Furthermore, careers and earning potential have also been shown to be impacted by the burden of living with CHE. 36 About Atopic Dermatitis Atopic dermatitis is a chronic, inflammatory skin disease characterized by intense itch and eczematous lesions. 37 Atopic dermatitis is the result of skin barrier dysfunction and immune dysregulation, leading to chronic inflammation. 38 Type 2 cytokines, including IL-13, play an important role in the key aspects of atopic dermatitis pathophysiology. 37,38 Excessive IL-22 production is also known to contribute to the pathogenesis of AD. 39 About Psoriasis Psoriasis is a chronic, systemic inflammatory disease that primarily affects the skin in 125 million people worldwide. 40,41 Psoriasis is the result of skin barrier cell proliferation and the activation of cytokines (a family of proteins involved in immune responses) that cause inflammation. 42 About 80% to 90% of patients are affected by plaque psoriasis, the most common clinical form of psoriasis. 43 The symptoms of plaque psoriasis are itchy or painful raised scaly and inflamed plaques. Plaques may appear anywhere on the body, but often appear on the scalp, knees, elbows and torso. 43 About Anzupgo ® (delgocitinib) cream Anzupgo ® (delgocitinib) cream 20 mg/g 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. 44 The pathophysiology is characterized by skin barrier dysfunction, inflammation of the skin, and alterations of the skin microbiome. 45 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 Adtralza ® (tralokinumab) / Adbry ® (tralokinumab-ldrm) Adtralza ® (tralokinumab), which is marketed under the tradename Adbry ® in the U.S., is a high-affinity fully human monoclonal antibody developed to bind to and inhibit the interleukin IL-13 cytokine, which plays a role in the immune and inflammatory processes underlying atopic dermatitis signs and symptoms. 38,46 Adtralza ® specifically binds to the IL-13 cytokine, thereby inhibiting interaction with the IL-13 receptor α1 and α2 subunits (IL-13Rα1 and IL-13Rα2). 47 Adtralza ® is approved for the treatment of moderate to severe AD in adult and adolescent patients 12 years and older in the European Union, Canada, Great Britain, the United Arab Emirates, and South Korea. Adtralza ® is approved for use in adults with moderate to severe AD in the U.S., Switzerland, Saudi Arabia, and Japan. About Kyntheum ® (brodalumab) Kyntheum ® (brodalumab) is a recombinant fully human monoclonal immunoglobulin IgG2 antibody that binds with high affinity to human IL-17RA and blocks the biological activities of the pro-inflammatory cytokines IL-17A, IL-17F, IL-17A/F heterodimer, IL-17C and IL-17E (also known as IL-25), resulting in inhibition of the inflammation and clinical symptoms associated with psoriasis. IL-17RA is a protein expressed on the cell surface and is a required component of receptor complexes utilized by multiple IL-17 family cytokines. IL-17 family cytokine levels have been reported to be increased in psoriasis. IL-17A, IL-17F and IL-17A/F heterodimer have pleiotropic activities including the induction of pro-inflammatory mediators such as IL-6, GROα, and G-CSF from epithelial cells, endothelial cells and fibroblasts that promote tissue inflammation. IL-17C has been shown to induce similar responses as IL-17A and IL-17F in keratinocytes. Blocking IL-17RA inhibits IL-17 cytokine-induced responses resulting in normalization of inflammation in the skin. 48 Kyntheum ® is indicated in the European Union, Great Britain, the United Arab Emirates, and Brazil for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy. About temtokibart Temtokibart (LEO 138559) is an investigational monoclonal antibody that targets the IL-22RA1 receptor subunit, currently in Phase 2 development for the potential treatment of moderate to severe atopic dermatitis. 49 It blocks the IL-22RA1 subunit and thereby inhibits the effects of the IL-22 cytokine, and potentially also to some extent the effects of IL-20 and IL-24. 49 Temtokibart does not bind to the IL-22 cytokine itself. 49 LEO Pharma has obtained a worldwide exclusive license to develop and commercialize temtokibart from argenx. 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: A 24-week head-to-head phase 3 trial comparing the efficacy and safety of topical delgocitinib cream with oral alitretinoin capsules in adults with severe chronic hand eczema. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation. D1T01.1F. Bisonnette R, Schliemann S, Gooderham M, et al. Treatment response of delgocitinib cream according to Chronic Hand Eczema (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 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. EPoster Presentation. P2559 Fargnoli MN, Molin S, Bewley A, et al. The multifactorial and heterogenous nature of Chronic Hand Eczema 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. EPoster Presentation. P0608. Worm M, Jiang L, Litman T, et al. Topical pan-JAK inhibition with delgocitinib restores the molecular signature of lesional skin in patients with Chronic Hand. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation. P0572. Bewley A, Molin S, Crepy MN, et al. Health-related quality of life in people with Chronic Hand Eczema - Findings from the multi-national CHECK study. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P3443. Mohandas P, Devani AR, Baranowski K, et al. Clinical trial exit interviews in patients with moderate to severe Chronic Hand Eczema: 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. EPoster Presentation. P0532. Pezzolo E, Cork M, Beecker J, et al. Real-world effectiveness of tralokinumab in adults with atopic dermatitis: Interim data on improvements in physician-assessed disease severity after up to 9 months of follow-up in the TRACE study. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P0689. Costanzo A, Becherel PA, Serra E, et al. Real-world effectiveness of tralokinumab in adults with atopic dermatitis: Interim data on improvements in patient-reported outcomes after up to 9 months of follow-up in the TRACE study. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P0690. Escalas J, Armesto S, Abalde T, et al. Observational study to assess the real-life descriptive effectiveness in patients with moderate to severe plaque psoriasis treated with Brodalumab stratified by patients with BMI>30 and patients with BMI ≤ 30. The BROACTIVE Study. 2 years - results. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P3205. Panagakis P, Chasapi V, Kalapothakou K, et al. Long-term management outcome assessment of adult patients with moderate-to-severe plaque psoriasis treated with brodalumab in Greece: The ReSOLVE study. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P3102. Thaçi D, Bangert C, Laquer V, et al. Individual responses to IL-22RA1 inhibition in Asian patients with moderate-to-severe atopic dermatitis in Phase 1 and 2a clinical trials. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P0691. Blauvelt A, Merola J, Carrascosa JM, et al. Long-term safety and efficacy of tralokinumab in patients 65 years or older with moderate-to-severe atopic dermatitis. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P0479. Bauer A, Schuttelaar ML, Baranowski K, et al. Delgocitinib cream reduces itch and pain in adults with moderate to severe Chronic Hand Eczema: pooled analyses of the Phase 3 DELTA 1 and 2 trials. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P0564. Schuttelaar ML, Bisonnette R, Worm M, et al. Efficacy and of delgocitinib cream in adults with moderate to severe Chronic Hand Eczema: pooled results of the Phase 3 DELTA 1 and 2 trials. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P0569. Gooderham M, Thaçi D, Damgaard T, et al. Systemic exposure and safety profile of delgocitinib cream in adults with moderate to severe Chronic Hand Eczema in the Phase 3 DELTA 2 trial. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P0581. Molin S, Gooderham M, Bisonnette R, 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 European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P0565. Crepy MN, Molin S, Giménez-Arnau AM, et al. Association and impact of Chronic Hand Eczema on occupational and household/leisure activities– results from the multinational CHECK study. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P1076. Apfelbacher C, Bewley A, Molin S, et al. Prevalence of Chronic Hand Eczema in adults: A cross-sectional multi-national study of over 60,000 respondents in the general population. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P1901. Giménez-Arnau AM, Bewley A, Apfelbacher C et al. Treatment patterns in moderate to severe Chronic Hand Eczema - Results from the multinational RWEAL medical chart review. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P3568. Molin S, Fargnoli MN, Crepy MN, et al. Self-reported disease severity and treatment of Chronic Hand Eczema from the CHECK study - A multinational study in six countries. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P3526 . Chovatiya R, Wollenberg A, Ribero S, et al. Improvement of the head and neck regions with continuous tralokinumab treatment for up to 4 years in adults with moderate-to-severe atopic dermatitis. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P0595. Soung J, Laquer V, Zirwas M, et al. Tralokinumab formulated as a pre-filled pen was efficacious and well-tolerated in adults and adolescents with moderate-to-severe atopic dermatitis. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P0574. Blauvelt A, Hong HC, Peris K, et al. Stability of long-term therapeutic responses to tralokinumab in adults with moderate-to-severe atopic dermatitis. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. EPoster Presentation. P0596. Cohen D, Bewley A, Wollenberg A, et al. Matching-adjusted indirect comparison of the efficacy of delgocitinib and dupilumab in the treatment of moderate to severe atopic hand eczema. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation.D3T01.4B. Senna MM, Soerensen OE, Nielsen AB et al. Randomized vehicle-controlled clinical trial with the topical JAK inhibitor delgocitinib in patients with frontal fibrosing alopecia demonstrates biomarker and clinical efficacy. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation. D3T01.4F. Armstrong A, Ameen A, Bagel J et al. Real-world effectiveness of tralokinumab in adults with atopic dermatitis: Interim data on improvements in patients with head and neck atopic dermatitis after up to 9 months of treatment in the TRACE study. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation. D3T01.3C Bangert C, Berdyshev E, Alkon N et al. Targeting IL-22RA1 with temtokibart in patients with moderate to severe atopic dermatitis induces fast clinical and molecular responses, distinct from dupilumab. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation. D2T01.3A. 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. Diepgen TL, et al. Guidelines for diagnosis, prevention and treatment of hand eczema. J Dtsch Dermatol Ges. 2015 Jan;13(1):e1–22. 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 Bissonnette R, et al. Redefining treatment options in chronic hand eczema (CHE). JEADV . 2010;24;1–20. 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. 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. Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387(10023):1109-1122. Boguniewicz M, Leung DY. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242(1):233-246. Dudakov JA, Hanash AM, van den Brink MR. Interleukin-22: immunobiology and pathology. Annu Rev Immunol . 2015;33:747-785. Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol 2009; 60: 643-659. Psoriasis Statistics. National Psoriasis Foundation website. https://www.psoriasis.org/content/statistics . Accessed September, 2024. Hawkes JE, Chan TC, Krueger JG. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol. 2017;140(3):645-653. Plaque Psoriasis. National Psoriasis Foundation website. https://www.psoriasis.org/plaque/ . Updated September 2020. Accessed August 16, 2024. 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. Bieber T. Interleukin-13: targeting an underestimated cytokine in atopic dermatitis. Allergy . 2020; 75:54-62. Popovic B, Breed J, Rees DG, et al. Structural Characterisation Reveals Mechanism of IL-13-Neutralising Monoclonal Antibody Tralokinumab as Inhibition of Binding to IL-13Rα1 and IL-13Rα2. J Mol Biol. 2017;429(2):208-219. Electronic Medicines Compendium. SmPC. Kyntheum (brodalumab). 10 Jan 2023. https://www.ema.europa.eu/en/documents/product-information/kyntheum-epar-product-information_en.pdf Accessed September, 2024. Thaçi D, et al. Efficacy and safety of IL-22R inhibition in patients with moderate-to-severe atopic dermatitis: results from a phase 2a monotherapy trial. Presented at the 2023 American Academy of Dermatology Annual Meeting; March 17–21 2023; New Orleans, LA. MAT-76322 September 2024

Phase 3Clinical ResultDrug ApprovalLicense out/inPhase 2

03 May 2024

·www.fiercepharma.com

Leo Pharma prepares to come for the topical JAK market as Incyte's Opzelura cream launch cools off

None Watch out, Incyte. Leo Pharma and its JAK inhibitor cream delgocitinib are coming to disrupt the topical atopic dermatitis market, currently inhibited by Incyte’s approved Opzelura. With several positive studies in hand, including a recent phase 3 trial pitting the candidate against the current standard-of-care, Leo says its delgocitinib has growth driver potential. Now, the drugmaker will be “investing additional resources in accelerating the launch of this potential treatment to patients,” Leo said in its first quarter earnings release. The cream is currently under regulatory review in Europe. As for other markets including the U.S., Leo is “assessing ways” to bring the potential treatment to commercialization, it said. Delgocitinib has been marked in Japan by Japan Tobacco for four years now. Leo's evidence supporting the drug includes two phase 3 studies against a placebo cream and an open-label extension study proving its success in treating patients with moderate-to-severe chronic hand eczema. Most recently, delgocitinib went up against standard-of-care alitretinoin capsules, the only currently approved treatment for chronic hand eczema patients who do not respond to topical corticosteroids. In the DELTA FORCE study of 513 patients, Leo’s candidate proved a superior reduction in scoring on the Hand Eczema Severity Index at week 12 and week 24. It also trumped alitretinoin in two other secondary measures assessing treatment success and quality of life. “We are confident that with the DELTA FORCE study, delgocitinib cream may play a crucial role in expanding the options available for patients in this hard-to-treat condition,” chief development officer Kreesten Meldgaard Madsen said at the time. If the drug scores approval, it would compete with the only other marketed topical JAK inhibitor, Incyte’s Opzelura. That med is a cream version of the company’s popular JAK inhibitor Jakafi. Other than atopic dermatitis, Opzelura is also approved to treat vitiligo. Incyte is now moving to expand the Jakafi counterpart into pediatric atopic dermatitis use and expects to submit its bid for the indication this year along with “multiple data readouts,” head of R&D Pablo Cagnoni said on the company’s first-quarter earnings call. A pediatric nod would add some two million to three million eligible patients to the med’s reach, the company said. Opzelura and Jakafi brought Incyte to blockbuster fourth-quarter sales last year, reflecting what the company’s North America general manager Barry Flannelly called “one of the best recent dermatology launches” on Opzelura’s part following its 2021 approval. More recently over this year’s first quarter, sales for both Opzelura and Jakafi sank on a quarterly basis, missing analyst’s consensus. While Jakafi was impacted by higher inventory drawdown and Opzelura by Change Helathcare’s cyberattack, the explanations “still will not provide investors with data point to suggest there is upside to estimates in the near term,” analysts at William Blair wrote in a note to clients. Opzelura pulled first-quarter revenues of $86 million, dipping 21.5% from the fourth quarter.

Phase 3Drug ApprovalClinical Result

100 Deals associated with Alitretinoin

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KEGG	Wiki	ATC	Drug Bank
D02815	Alitretinoin	L01XX22 D11AH04	DB00523

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
AIDS-related Kaposi Sarcoma	US	Concordia Pharmaceuticals, Inc.	02 Feb 1999

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Promyelocytic Leukemia	Discovery	US	Ligand Pharmaceuticals, Inc.	30 Jun 1999
Head and Neck Neoplasms	Discovery	US	Ligand Pharmaceuticals, Inc.	27 Aug 1996
Ovarian Cancer	Discovery	US	Ligand Pharmaceuticals, Inc.	27 Aug 1996
Squamous Cell Carcinoma	Discovery	US	Ligand Pharmaceuticals, Inc.	27 Aug 1996
Kidney Neoplasms	Discovery	CA	Ligand Pharmaceuticals, Inc.	23 May 1995
Non-Hodgkin Lymphoma	Discovery	US	Ligand Pharmaceuticals, Inc.	23 May 1995

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05259722 (BusinessWire) Manual	Phase 3	Chronic eczema	513	Delgocitinib cream	jfngwidpps(qkdzmatffo) = vtqjvpnynz pqnvxtwjpx (rxsyxklxak ) Met View more	Positive	25 Sep 2024
				Alitretinoin capsules	jfngwidpps(qkdzmatffo) = zrrveodcgq pqnvxtwjpx (rxsyxklxak ) Met View more
NCT00817063 (HANDEL, CTgov)	Phase 3	Chronic eczema	599	Placebo	qtcdpgxmsm(tiymqxcylr) = hujkkywksi zkxdznnyyr (ueexwpfmvg, nlvauvviss - egsatkofda) View more	-	09 Nov 2017
NCT01245140 (CTgov)	Phase 2	Pustular psoriasis	33	placebo (Matching Placebo)	hhjrbpgyet(kfbczamjmd) = wrubpnldeu molmbrslrp (tobgqmlmfo, ccoppfckcr - qlzfstqiep) View more	-	04 Apr 2017
				Alitretinoin (Alitretinoin 30 mg)	hhjrbpgyet(kfbczamjmd) = qfigdpjhzp molmbrslrp (tobgqmlmfo, lehhymzotr - ldvjtjkrgf) View more
NCT00817063 (Pubmed)	Phase 3	Eczema	596	Alitretinoin 30 mg	(upwanrnjad) = bhyyhbabhp jjjwoemlwa (qpkvphzfow ) View more	Positive	01 Oct 2014
				Placebo	(bmkknlxkld) = ojseuqjpua dnzzyltdnx (riebmwarrz )
NCT00609739 (CTgov)	Phase 1/2	Juvenile Myelomonocytic Leukemia	1	umbilical cord blood transplantation+methylprednisolone+Cis-Retinoic acid+cyclosporine+Filgrastim+mitoxantrone hydrochloride+methotrexate+Cytarabine	(stvqzqiqzt) = mwvzwmrqns oyyqwfytjt (ujtjsxaqwt, lpwthnmwfn - nioyanylsh) View more	-	02 Mar 2012
ASCO2010	Not Applicable	Glioblastoma Multiforme Adjuvant	79	Temozolomide + cis-retinoic acid	(wxrwcrssaa) = zlmwsogdxs kpewjpthcs (yeroqzcsvr ) View more	-	20 May 2010
ARVO2003	Not Applicable	-	-	9-cis retinoic acid	qfhlwumqkj(vrgwhsyoqt) = vemnnrusim blqiyngzpl (yjiqfyuvze )	-	01 May 2003
				11-cis retinoic acid	qfhlwumqkj(vrgwhsyoqt) = pbwhqhbwfm blqiyngzpl (yjiqfyuvze )

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