Letter to the Editor
Fevipiprant, a selective prostaglandin D2 receptor 2 antagonist, inhibits human group 2 innate lymphoid cell aggregation and function

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Cited by (9)

  • The pharmacology of the prostaglandin D<inf>2</inf> receptor 2 (DP<inf>2</inf>) receptor antagonist, fevipiprant

    2021, Pulmonary Pharmacology and Therapeutics
    Citation Excerpt :

    In recent years ILC2 have been recognised as an important DP2-dependent new effector cell type in uncontrolled asthma [29], with increased numbers of ILC2s found in the blood and sputum of patients with severe therapy-resistant asthma [48]. DP2 receptor antagonism with fevipiprant reduces PGD2 induced ILC2 migration and type 2 cytokine production (IL-4, IL-5, IL-13) and non-type 2 cytokine production (IL-8, CSF-1 and GM-CSF), neutralises the effect of PGD2 on ILC2 survival, and blocks ILC2 cell aggregation, with similar potencies observed in samples derived from patients with both mild and severe asthma [49]. Recently, blood and airway levels of Tc2 have been shown to be increased in uncontrolled eosinophilic asthma patients, in addition to displaying DP2-mediated functions such as increased type 2 cytokine production [20].

  • Efficacy and safety of fevipiprant in patients with uncontrolled asthma: Two replicate, phase 3, randomised, double-blind, placebo-controlled trials (ZEAL-1 and ZEAL-2)

    2021, EClinicalMedicine
    Citation Excerpt :

    PGD2 is a major prostanoid inflammatory mediator identified in asthma. By binding to the DP2 receptor, fevipiprant inhibits the migration and activation of eosinophils, basophils, ILC-2 (type 2 innate lymphoid cells) and T lymphocytes into the airway tissues and blocks the PGD2-driven release of Th2 cytokines [5,6]. In a phase 2 ‘proof-of-concept’ study in a subgroup of patients with reduced lung function at baseline, treatment with fevipiprant 500 mg once daily showed significant improvements in pre-dose trough FEV1 and Asthma Control Questionnaire (ACQ) scores compared with placebo [7].

  • New treatments for asthma: From the pathogenic role of prostaglandin D<inf>2</inf> to the therapeutic effects of fevipiprant

    2020, Pharmacological Research
    Citation Excerpt :

    Fevipiprant dissociates slowly from human CRTH2 and effectively suppresses Th2 cell synthesis of IL-4, IL-15 and IL-13 [57]. Moreover, with regard to key ILC2 functions, fevipiprant is able to effectively inhibit cell migration, aggregation, survival and cytokine (IL-4, IL-5, IL-13) production [59]. In addition to affecting the biological activities of immune-inflammatory cells such as Th2 lymphocytes and ILC2, fevipiprant can also extend its inhibitory actions on airway structural cells (Fig. 1).

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Supported by a research grant to G.O. and L.X. from Novartis administered through the University of Oxford. The views expressed are those of the authors and not necessarily those of the National Health Service, the National Institute of Health Research (NIHR), or the Department of Health.

Disclosure of potential conflict of interest: I. D. Pavord has received speaker's honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, and GlaxoSmithKline and payments for organizing educational events from AstraZeneca, GlaxoSmithKline, Sanofi/Regeneron, and Teva; has received honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Teva, Merck, Circassia, Chiesi, and Knopp; and received payments to support US Food and Drug Administration approval meetings from GlaxoSmithKline; has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Teva, and Chiesi; has received a grant from Chiesi to support a phase 2 clinical trial in Oxford; and was an expert witness in 2014-2105 for a patent dispute involving Astra Zeneca and Teva. V. J. Erpenbeck is a former employee of Novartis. D. A. Sandham is a current employee of Novartis. G. Ogg has received research grants and consultancies or served on advisory boards for UCB, Celgene, AnaptysBio, Sanofi/Genzyme, La Roche Posay, Orbit Discovery, Grunenthal, Evelo, Eli Lilly, and Leo. The rest of the authors declare that they have no relevant conflicts of interest.

These authors contributed equally to this work.

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