학술논문
Orismilast in moderate-to-severe psoriasis: Efficacy and safety from a 16-week, randomized, double-blinded, placebo-controlled, dose-finding, and phase 2b trial (IASOS).
Document Type
Academic Journal
Author
Warren RB; Dermatology Centre, Northern Care Alliance NHS Foundation Trust, Manchester, United Kingdom; NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. Electronic address: richard.warren@manchester.ac.uk.; French LE; Department of Dermatology and Allergy, University Hospital, Ludwig Maximilian University Munich, Munich, Germany; Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida.; Blauvelt A; Oregon Medical Research Center, Portland, Oregon.; Langley RG; Division of Dermatology, Dalhousie University, Halifax, Canada.; Egeberg A; Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Mrowietz U; Psoriasis-Center, Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany.; Hunter HJA; Dermatology Centre, Northern Care Alliance NHS Foundation Trust, Manchester, United Kingdom; NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; Medicines Evaluation Unit, Manchester, United Kingdom.; Gooderham M; SKiN Centre for Dermatology, Peterborough, Canada; Department of Medicine, Queen's University, Kingston, Canada.; Soerensen P; UNION Therapeutics A/S, Hellerup, Denmark.; Andres P; UNION Therapeutics A/S, Hellerup, Denmark.; Sommer MOA; UNION Therapeutics A/S, Hellerup, Denmark; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.; Carlsson A; UNION Therapeutics A/S, Hellerup, Denmark.; Kjøller KD; UNION Therapeutics A/S, Hellerup, Denmark.; Strober BE; Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut; Central Connecticut Dermatology Research, Cromwell, Connecticut.
Source
Publisher: Mosby Country of Publication: United States NLM ID: 7907132 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-6787 (Electronic) Linking ISSN: 01909622 NLM ISO Abbreviation: J Am Acad Dermatol Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Orismilast is a novel oral phosphodiesterase-4 (PDE4) B/D inhibitor being investigated as a potential treatment for moderate-to-severe psoriasis.
Objective: To evaluate efficacy and safety of orismilast modified-release formulation in moderate-to-severe psoriasis.
Methods: This multicenter, randomized (1:1:1:1 to 20, 30, 40 mg orismilast or placebo, twice daily), double-blinded, placebo-controlled, parallel-group, phase 2b, 16-week, dose-ranging study evaluated orismilast in adults with moderate-to-severe plaque psoriasis (NCT05190419). Efficacy end points were analyzed using multiple imputation.
Results: Of 202 randomized patients, baseline characteristics were balanced across arms, except greater severe disease proportions for orismilast vs placebo. Orismilast showed significant improvements in the primary end point, percentage change in Psoriasis Area and Severity Index (PASI), from baseline to week 16 (orismilast -52.6% to -63.7% and placebo, -17.3%; all P <.001). Greater proportions receiving orismilast achieved PASI75 (39.5%-49.0%; P <.05) and PASI90 (22.0%-28.3%; P <.05 for 20 and 40 mg) vs placebo (PASI75, 16.5% and PASI90, 8.3%) at week 16. Safety findings were as expected with PDE4 inhibition; dose-dependent tolerability effects observed.
Limitations: Small sample size, disease severity imbalance between groups, limited duration and diversity in study population.
Conclusion: Orismilast demonstrated greater efficacy vs placebo and a safety profile in line with PDE4 inhibition.
Competing Interests: Conflicts of interest Dr Warren has received research grants from AbbVie, Almirall, Amgen, Celgene, Janssen, Lilly, Leo Pharma, Novartis, Pfizer, and UCB, and consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, GlaxoSmithKline, Janssen, Lilly, Leo Pharma, Novartis, Pfizer, Sanofi, Sun Pharma, UCB, and UNION therapeutics. Dr French has received consulting fees and/or honoraria from AbbVie, AC Immune, Almirall, Amgen, Biotest, Eli Lilly, Galderma, InflaRx, Janssen, Leo Pharma, Novartis, Regeneron, UCB, UNION therapeutics, and Vaderis Therapeutics, and has served as president of the International League of Dermatological Societies. Dr Blauvelt has received research grants from AbbVie, Acelyrin, Allakos, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly, Evelo, Evommune, Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, UCB Pharma, and Ventyx, and honoraria from AbbVie, Abcentra, Aclaris, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Apogee, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, CTI BioPharma, Dermavant, EcoR1, Eli Lilly, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, Leo Pharma, Lipidio, Merck, Monte Rosa Therapeutics, Nektar, Novartis, Overtone Therapeutics, Pfizer, Rani, Rapt, Regeneron, Sanofi, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, Takeda, TLL Pharmaceutical, TrialSpark, UCB Pharma, UNION therapeutics, Ventyx, Vibliome, and Xencor. Dr Langley has received honoraria from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Ortho Dermatologics, Pfizer, Sanofi Genzyme, Sun Pharma, and UCB. Dr Egeberg has received research grants from AbbVie, Danish National Psoriasis Foundation, Eli Lilly, Janssen, Kgl Hofbundtmager Aage Bangs Foundation, Novartis, Pfizer, Boehringer Ingelheim, and Simon Spies Foundation, and consulting fees and/or honoraria and/or travel bursaries from AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Galderma, Galapagos NV, Horizon Therapeutics, Janssen, Leo Pharma, Mylan, Novartis, Pfizer, Samsung Bioepis Co Ltd, UCB, and UNION therapeutics. Dr Mrowietz has received honoraria from UNION therapeutics. Dr Hunter has received grant funding from Janssen, Merck Serono, and Pfizer, honoraria and/or consultancy fees and/or travel bursaries from AbbVie, Almirall, DICE Therapeutics, Eli Lilly, Janssen, La Roche-Posay, Leo Pharma, Novartis, Regeneron, Sanofi Genzyme, UCB, and UNION therapeutics, and has acted as an investigator for AbbVie, Almirall, Bayer Pharmaceuticals, DICE Therapeutics, Eli Lilly, Evelo Biosciences Inc, Janssen, Leo Pharma, Novartis, ONO Pharmaceutical Co Ltd, Sanofi Genzyme, UCB, and UNION therapeutics. Dr Gooderham has received research grants from AbbVie, Akros Pharma Inc, Amgen, Arcutis Pharmaceuticals Inc, Asana Bio Sciences, AnaptysBio, Aristea, Bausch Health, Boehringer Ingelheim International, Bristol Myers Squibb, Celgene, Coherus Biosciences, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin, Leo Pharma, MedImmune, Merck, Meiji, Moonlake, Novartis, Nimbus Therapeutics, Pfizer, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Tarsus, Takeda, UCB, and Ventyx, consulting fees and/or honoraria and/or travel bursaries from AbbVie, Akros Pharma, Amgen, Arcutis Pharmaceuticals Inc, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, and UNION therapeutics, and is the owner of a phototherapy center. Author Soerensen is an employee of UNION therapeutics. Dr Andres has received consulting fees from UNION therapeutics. Dr Sommer is an employee and shareholder of UNION therapeutics, received consulting fees from UNION therapeutics, patents with UNION therapeutics, and serves as a board member of UNION therapeutics. Author Carlsson is an employee of UNION therapeutics. Dr Kjøller is an employee of and shareholder in UNION therapeutics, and serves as chairman of the Danish Life Science Cluster. Strober has received consulting fees and/or honoraria from AbbVie, Alamar, Almirall, Alumis, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Capital One, Connect Biopharma, CorEvitas, Dermavant, Eli Lilly, Evelo Biosciences, Immunic Therapeutics, Incyte, Janssen, Kangpu Pharmaceuticals, Leo Pharma, Maruho, Meiji Seika Pharma, Mindera Health, Nimbus, Novartis, Pfizer, Protagonist, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, UNION therapeutics, Ventyxbio, and vTv Therapeutics, shareholder in Connect Biopharma, and Mindera Health, serves as scientific codirector of CorEvitas Psoriasis Registry, and serves as editor-in-chief of the Journal of Psoriasis and Psoriatic Arthritis.
(Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
Objective: To evaluate efficacy and safety of orismilast modified-release formulation in moderate-to-severe psoriasis.
Methods: This multicenter, randomized (1:1:1:1 to 20, 30, 40 mg orismilast or placebo, twice daily), double-blinded, placebo-controlled, parallel-group, phase 2b, 16-week, dose-ranging study evaluated orismilast in adults with moderate-to-severe plaque psoriasis (NCT05190419). Efficacy end points were analyzed using multiple imputation.
Results: Of 202 randomized patients, baseline characteristics were balanced across arms, except greater severe disease proportions for orismilast vs placebo. Orismilast showed significant improvements in the primary end point, percentage change in Psoriasis Area and Severity Index (PASI), from baseline to week 16 (orismilast -52.6% to -63.7% and placebo, -17.3%; all P <.001). Greater proportions receiving orismilast achieved PASI75 (39.5%-49.0%; P <.05) and PASI90 (22.0%-28.3%; P <.05 for 20 and 40 mg) vs placebo (PASI75, 16.5% and PASI90, 8.3%) at week 16. Safety findings were as expected with PDE4 inhibition; dose-dependent tolerability effects observed.
Limitations: Small sample size, disease severity imbalance between groups, limited duration and diversity in study population.
Conclusion: Orismilast demonstrated greater efficacy vs placebo and a safety profile in line with PDE4 inhibition.
Competing Interests: Conflicts of interest Dr Warren has received research grants from AbbVie, Almirall, Amgen, Celgene, Janssen, Lilly, Leo Pharma, Novartis, Pfizer, and UCB, and consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, GlaxoSmithKline, Janssen, Lilly, Leo Pharma, Novartis, Pfizer, Sanofi, Sun Pharma, UCB, and UNION therapeutics. Dr French has received consulting fees and/or honoraria from AbbVie, AC Immune, Almirall, Amgen, Biotest, Eli Lilly, Galderma, InflaRx, Janssen, Leo Pharma, Novartis, Regeneron, UCB, UNION therapeutics, and Vaderis Therapeutics, and has served as president of the International League of Dermatological Societies. Dr Blauvelt has received research grants from AbbVie, Acelyrin, Allakos, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly, Evelo, Evommune, Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, UCB Pharma, and Ventyx, and honoraria from AbbVie, Abcentra, Aclaris, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Apogee, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, CTI BioPharma, Dermavant, EcoR1, Eli Lilly, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, Leo Pharma, Lipidio, Merck, Monte Rosa Therapeutics, Nektar, Novartis, Overtone Therapeutics, Pfizer, Rani, Rapt, Regeneron, Sanofi, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, Takeda, TLL Pharmaceutical, TrialSpark, UCB Pharma, UNION therapeutics, Ventyx, Vibliome, and Xencor. Dr Langley has received honoraria from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Ortho Dermatologics, Pfizer, Sanofi Genzyme, Sun Pharma, and UCB. Dr Egeberg has received research grants from AbbVie, Danish National Psoriasis Foundation, Eli Lilly, Janssen, Kgl Hofbundtmager Aage Bangs Foundation, Novartis, Pfizer, Boehringer Ingelheim, and Simon Spies Foundation, and consulting fees and/or honoraria and/or travel bursaries from AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Galderma, Galapagos NV, Horizon Therapeutics, Janssen, Leo Pharma, Mylan, Novartis, Pfizer, Samsung Bioepis Co Ltd, UCB, and UNION therapeutics. Dr Mrowietz has received honoraria from UNION therapeutics. Dr Hunter has received grant funding from Janssen, Merck Serono, and Pfizer, honoraria and/or consultancy fees and/or travel bursaries from AbbVie, Almirall, DICE Therapeutics, Eli Lilly, Janssen, La Roche-Posay, Leo Pharma, Novartis, Regeneron, Sanofi Genzyme, UCB, and UNION therapeutics, and has acted as an investigator for AbbVie, Almirall, Bayer Pharmaceuticals, DICE Therapeutics, Eli Lilly, Evelo Biosciences Inc, Janssen, Leo Pharma, Novartis, ONO Pharmaceutical Co Ltd, Sanofi Genzyme, UCB, and UNION therapeutics. Dr Gooderham has received research grants from AbbVie, Akros Pharma Inc, Amgen, Arcutis Pharmaceuticals Inc, Asana Bio Sciences, AnaptysBio, Aristea, Bausch Health, Boehringer Ingelheim International, Bristol Myers Squibb, Celgene, Coherus Biosciences, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin, Leo Pharma, MedImmune, Merck, Meiji, Moonlake, Novartis, Nimbus Therapeutics, Pfizer, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Tarsus, Takeda, UCB, and Ventyx, consulting fees and/or honoraria and/or travel bursaries from AbbVie, Akros Pharma, Amgen, Arcutis Pharmaceuticals Inc, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, and UNION therapeutics, and is the owner of a phototherapy center. Author Soerensen is an employee of UNION therapeutics. Dr Andres has received consulting fees from UNION therapeutics. Dr Sommer is an employee and shareholder of UNION therapeutics, received consulting fees from UNION therapeutics, patents with UNION therapeutics, and serves as a board member of UNION therapeutics. Author Carlsson is an employee of UNION therapeutics. Dr Kjøller is an employee of and shareholder in UNION therapeutics, and serves as chairman of the Danish Life Science Cluster. Strober has received consulting fees and/or honoraria from AbbVie, Alamar, Almirall, Alumis, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Capital One, Connect Biopharma, CorEvitas, Dermavant, Eli Lilly, Evelo Biosciences, Immunic Therapeutics, Incyte, Janssen, Kangpu Pharmaceuticals, Leo Pharma, Maruho, Meiji Seika Pharma, Mindera Health, Nimbus, Novartis, Pfizer, Protagonist, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, UNION therapeutics, Ventyxbio, and vTv Therapeutics, shareholder in Connect Biopharma, and Mindera Health, serves as scientific codirector of CorEvitas Psoriasis Registry, and serves as editor-in-chief of the Journal of Psoriasis and Psoriatic Arthritis.
(Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)