{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:25:19Z","timestamp":1793165119959,"version":"4.5.0"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF20CC0035580"],"award-info":[{"award-number":["NNF20CC0035580"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Orismilast is a high\u2010potency phosphodiesterase 4 (PDE4) inhibitor with enhanced selectivity for the PDE4B and PDE4D subtypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The objective of this phase 2a trial was to examine the efficacy and safety of orismilast for psoriasis using a first\u2010generation immediate\u2010release (IR) formulation. The objective of the subsequent phase 1 trial was to test new formulations designed to minimize the gastrointestinal (GI)\u2010related adverse events (AEs) observed with the first\u2010generation IR formulation. We examined the following: (1) pharmacokinetic (PK) properties of orismilast modified release (MR) and IR, (2) food effects on PK properties of orismilast MR or IR, (3) safety of orismilast MR compared to placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a phase 2a prospective, randomized, double\u2010blind, placebo\u2010controlled trial, patients with moderate\u2010to\u2010severe psoriasis were randomized to receive 30\u2009mg oral orismilast IR or placebo over 16\u2009weeks. The single\u2010site phase 1 trial consisted of three parts: (1) participants received a single 30\u2009mg dose of orismilast MR and IR (open\u2010label), (2) participants received 30\u2009mg orismilast MR or IR under either fasting condition, following a high\u2010fat meal or low\u2010fat meal (open\u2010label) and (3) participants received up to 60\u2009mg orismilast MR twice\u2010daily or a placebo for 17\u2009days (double\u2010blind).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the phase 2a trial, treatment with orismilast IR significantly improved the mean Psoriasis Area Severity Index score at week 16 compared to placebo. The phase 1 trial revealed comparable PK properties of the orismilast MR and IR formulations, with participants in the orismilast MR group experiencing fewer GI\u2010related AEs than those receiving orismilast IR (16.7% vs. 33.3%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Orismilast IR displayed higher efficacy compared to placebo in patients with moderate\u2010to\u2010severe psoriasis at week 16. Orismilast MR had similar PK properties and fewer GI disorders compared to the IR formulation in healthy participants. Future development of orismilast will be based on the MR formulation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.18812","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T21:44:08Z","timestamp":1670449448000},"page":"711-720","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Oral orismilast: Efficacy and safety in moderate\u2010to\u2010severe psoriasis and development of modified release tablets"],"prefix":"10.1111","volume":"37","author":[{"given":"Richard B.","family":"Warren","sequence":"first","affiliation":[{"name":"Dermatology Centre Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8394-2057","authenticated-orcid":false,"given":"Bruce","family":"Strober","sequence":"additional","affiliation":[{"name":"Yale University and Central Connecticut Dermatology  Connecticut New Haven USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3686-7805","authenticated-orcid":false,"given":"Jonathan I.","family":"Silverberg","sequence":"additional","affiliation":[{"name":"George Washington University School of Medicine and Health Sciences  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9363-324X","authenticated-orcid":false,"given":"Emma","family":"Guttman","sequence":"additional","affiliation":[{"name":"Department of Dermatology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Andres","sequence":"additional","affiliation":[{"name":"UNION therapeutics A\/S  Hellerup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Felding","sequence":"additional","affiliation":[{"name":"UNION therapeutics A\/S  Hellerup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9390-6105","authenticated-orcid":false,"given":"Deniz","family":"Tutkunkardas","sequence":"additional","affiliation":[{"name":"UNION therapeutics A\/S  Hellerup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Kj\u00f8ller","sequence":"additional","affiliation":[{"name":"UNION therapeutics A\/S  Hellerup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten O. A.","family":"Sommer","sequence":"additional","affiliation":[{"name":"UNION therapeutics A\/S  Hellerup Denmark"},{"name":"Novo Nordisk Foundation Center for Biosustainability Technical University of Denmark  Kongens Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4629-1486","authenticated-orcid":false,"given":"Lars E.","family":"French","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy University Hospital, Ludwig Maximilian University (LMU) Munich  Munich Germany"},{"name":"Dr. Philip Frost, Department of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61128-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132710"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041257"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2016.01.007"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702387"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702911"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archdermatol.2012.812"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-022-00712-0"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2000073"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.740803"},{"key":"e_1_2_10_12_1","unstructured":"ClinicalTrials.gov.Identifier NCT02496546 an explorative trial evaluating the effect of LEO 32731 cream in adults with mild to moderate atopic dermatitis (AD).2017."},{"key":"e_1_2_10_13_1","unstructured":"ClinicalTrials.gov.Identifier: NCT04982432 Orismilast for the treatment of mild to severe hidradenitis suppurativa (OSIRIS). 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