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Pharmacokinetics and pharmacodynamics of itepekimab in adults with moderate-to-severe atopic dermatitis: Results from two terminated phase II trials.
Kosloski, Matthew P; Guttman-Yassky, Emma; Cork, Michael J; Worm, Margitta; Nahm, Dong-Ho; Zhu, Xiaoping; Ruddy, Marcella K; Harel, Sivan; Kamal, Mohamed A; Goulaouic, Hélène; Xu, Christine R; Avetisova, Elena; Davis, John D; Nivens, Michael C; Shabbir, Arsalan; Radin, Allen.
Affiliation
  • Kosloski MP; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Guttman-Yassky E; Icahn School of Medicine at Mount Sinai Medical Center, New York, New York, USA.
  • Cork MJ; Rockefeller University, New York, New York, USA.
  • Worm M; Sheffield Dermatology Research, University of Sheffield, Sheffield, UK.
  • Nahm DH; Sheffield Children's Hospital, Sheffield, UK.
  • Zhu X; Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Ruddy MK; Ajou University Hospital, Suwon, Korea.
  • Harel S; Formerly Regeneron Pharmaceuticals Inc., Basking Ridge, New Jersy, USA.
  • Kamal MA; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Goulaouic H; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Xu CR; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Avetisova E; Sanofi, Chilly-Mazarin, France.
  • Davis JD; Sanofi, Bridgewater, New Jersey, USA.
  • Nivens MC; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Shabbir A; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Radin A; Formerly Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Clin Transl Sci ; 17(8): e13874, 2024 Aug.
Article in En | MEDLINE | ID: mdl-39077906
ABSTRACT
Interleukin-33 (IL-33) is a proinflammatory alarmin cytokine released by damaged epithelial tissue cells that initiates and amplifies both type 1 and type 2 inflammatory cascades. A role for IL-33 in atopic dermatitis (AD; a chronic, relapsing type 2 inflammatory disease of the skin) has been proposed. Itepekimab is a novel human IgG4P monoclonal antibody against IL-33, currently in clinical development for chronic obstructive pulmonary disease (COPD). Two global phase II studies-a dose-ranging itepekimab monotherapy study (NCT03738423) and a proof-of-concept study of itepekimab alone and in combination with dupilumab (NCT03736967)-were conducted in patients with moderate-to-severe AD to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy; both studies were terminated following an interim analysis of the proof-of-concept study, which failed to demonstrate the efficacy of itepekimab. In these two studies, itepekimab exhibited linear and dose-proportional pharmacokinetics. Pharmacodynamics of total IL-33 indicated that itepekimab saturated binding to the target in serum at 300 mg q2w and q4w doses, and decreased blood eosinophil counts. Concentration-time profiles of itepekimab and total IL-33 were similar for itepekimab with or without dupilumab, and between East Asian and non-East Asian subgroups. Itepekimab was generally well tolerated, both alone and in combination with dupilumab. The lack of clinical efficacy for itepekimab observed in these studies suggests that IL-33 may not be a key pathogenic driver in moderate-to-severe AD.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Dermatitis, Atopic / Antibodies, Monoclonal, Humanized / Interleukin-33 Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: En Journal: Clin Transl Sci Year: 2024 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Dermatitis, Atopic / Antibodies, Monoclonal, Humanized / Interleukin-33 Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: En Journal: Clin Transl Sci Year: 2024 Document type: Article Affiliation country: Country of publication: