Fevipiprant, an oral prostaglandin DP receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids.

Eric D Bateman, Alfredo G Guerreros, Florian Brockhaus, Björn Holzhauer, Abhijit Pethe, Richard A Kay, Robert G Townley

Journal: The European respiratory journal 2018;50(2):1700670

PMID: 28838980

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Abstract

Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS).Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg ) or twice-daily (2, 25, 75 or 150 mg ) fevipiprant (n=782), montelukast 10 mg (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg Fevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg and 75 mg groups, with no clinically meaningful differences between and Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments.Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted.

Address: Division of Pulmonology, Dept of Medicine, University of Cape Town, Cape Town, South Africa [email protected].; Clinica Internacional, Lima, Peru.; Novartis Pharma AG, Basel, Switzerland.; Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.; Internal Medicine/Allergy, Creighton University, Omaha, NE, USA.; R.G. Townley sadly passed away before the submission of this manuscript.

DOI: 10.1183/13993003.00670-2017

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MeSH Terms: Acetates, Adult, Airway Management, Anti-Asthmatic Agents, Asthma, Budesonide, Cyclopropanes, Dose-Response Relationship, Drug, Drug Administration Routes, Drug Monitoring, Female, Forced Expiratory Volume, Glucocorticoids, Humans, Indoleacetic Acids, Male, Middle Aged, Pyridines, Quinolines, Receptors, Immunologic, Receptors, Prostaglandin, Severity of Illness Index, Sulfides, Treatment Outcome