Orismilast, a PDE4B/D inhibitor, in moderate-to-severe atopic dermatitis: Efficacy and safety from a multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (ADESOS)

Jonathan I. Silverberg, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Lawrence F. Eichenfield, Departments of Dermatology, Pediatric and Adolescent Dermatology, University of California, and Rady Children's Hospital, San Diego, CA, USA.
Andrew Blauvelt, Oregon Medical Research Center, Portland, OR, USA.
Alan D. Irvine, Clinical Medicine, Trinity College Dublin, Dublin, Ireland.
Emma Guttman-Yassky, Department of Dermatology and the Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Richard G. Langley, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Richard B. Warren, Northern Care Alliance NHS Foundation Trust and NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Lars E. French, Department of Dermatology and Allergy, Ludwig Maximilian University (LMU) Hospital Munich, Munich, Germany.
Jakob Felding, UNION therapeutics, A/S, Hellerup, Denmark.
Anne Weiss, UNION therapeutics, A/S, Hellerup, Denmark.
Claus B. Pedersen, UNION therapeutics, A/S, Hellerup, Denmark.
Morten L. Jensen, UNION therapeutics, A/S, Hellerup, Denmark.
Anna Carlsson, UNION therapeutics, A/S, Hellerup, Denmark.
Morten O. Sommer, UNION therapeutics, A/S, Hellerup, Denmark.
Kim Kjøller, UNION therapeutics, A/S, Hellerup, Denmark.
Eric L. Simpson, Department of Dermatology, Oregon Health & Science University, Portland, Oregon, USA.

Document Type

Journal Article

Publication Date

1-7-2025

Journal

The British journal of dermatology

DOI

10.1093/bjd/ljae507

Abstract

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by eczematous skin lesions and pruritus. There is an unmet need for effective first-line systemic therapies with good safety profiles, particularly oral medications. Orismilast is a novel first-in-class oral phosphodiesterase-4 (PDE4) B/D inhibitor under investigation for the treatment of moderate-to-severe AD. OBJECTIVES: To evaluate the optimal dose, efficacy and safety of orismilast twice-daily (BID) in patients with moderate-to-severe AD. METHODS: This 16-week, multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (NCT05469464) included patients from 48 centers in Europe and the United States. Adults with moderate-to-severe AD were given (1:1:1:1) BID orismilast 20, 30, or 40 mg, or placebo. The primary endpoint was percentage change in Eczema Area and Severity Index (EASI); secondary: achievement of a score of Clear (0) or Almost Clear (1) with ≥2-point improvement by Investigator Global Assessment (IGA 0/1); achievement of peak pruritus numerical rating scale (PPNRS) reduction of ≥4 points; and achievement of a reduction in EASI of 75%, 90%, and 100% (EASI75, EASI90, EASI100, respectively) from baseline; all week 16. RESULTS: Overall, 233 patients were randomly assigned to orismilast 20 mg (n=58), 30 mg (n=61), 40 mg (n=59), or placebo (n=55). At week 16, Reductions in EASI (%-point) from baseline to week 16 were seen across orismilast groups and placebo (p>0.05 for orismilast versus placebo). Significantly more patients achieved IGA 0/1 with a ≥2-point improvement with orismilast 20 mg and 40 mg versus placebo (p<0.05). Significantly greater proportions of patients achieving a ≥4-point reduction in PPNRS were demonstrated with orismilast at week 2. The safety profile was consistent with that of the PDE4 class, with no major safety concerns reported. CONCLUSIONS: These data support the clinical relevance of selective PDE4B/D inhibition with orismilast, potentially offering a convenient, novel, oral therapy for the treatment of AD.

Department

Dermatology

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