35 results match your criteria fevipiprant

The pharmacology of the prostaglandin D receptor 2 (DP) receptor antagonist, fevipiprant.

Pulm Pharmacol Ther 2021 Apr 4;68:102030. Epub 2021 Apr 4.

Novartis Pharmaceuticals Corporation, 1 Health Plaza, East Hanover, NJ, 07936, USA.

Fevipiprant is an oral, non-steroidal, highly selective, reversible antagonist of the prostaglandin D (DP) receptor. The DP receptor is a mediator of inflammation expressed on the membrane of key inflammatory cells, including eosinophils, Th2 cells, type 2 innate lymphoid cells, CD8 cytotoxic T cells, basophils and monocytes, as well as airway smooth muscle and epithelial cells. The DP receptor pathway regulates the allergic and non-allergic asthma inflammatory cascade and is activated by the binding of prostaglandin D. Read More

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Clinical Investigation of Metabolic and Renal Clearance Pathways Contributing to the Elimination of Fevipiprant Using Probenecid as Perpetrator.

Drug Metab Dispos 2021 May 25;49(5):389-394. Epub 2021 Feb 25.

Novartis Institutes for Biomedical Research, Basel, Switzerland (H.M.W., T.L., G.R., and B.P.); Novartis Institutes for Biomedical Research, Cambridge, Massachusetts (M.C.); Novartis Institutes for Biomedical Research, East Hanover, New Jersey (S.K. and B.S.); and Novartis Healthcare Pvt. Ltd., Hyderabad, India (J.V.).

Fevipiprant, an oral, nonsteroidal, highly selective, reversible, and competitive prostaglandin D receptor 2 antagonist, is eliminated by glucuronidation and by direct renal excretion predominantly via organic anion transporter (OAT) 3. This study aimed to assess the effect of simultaneous UDP-glucuronosyltransferase (UGT) and OAT3 inhibition by probenecid on the pharmacokinetics of fevipiprant and its acyl glucuronide (AG) metabolite to support the dosing recommendation of fevipiprant in the presence of drugs inhibiting these pathways; however, phase III clinical trial results did not support its submission. This was a single-center, open-label, single-sequence, two-period crossover study in healthy subjects. Read More

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Azaindole therapeutic agents.

Bioorg Med Chem 2020 12 30;28(24):115830. Epub 2020 Oct 30.

Department of Pharmacology and Chemical Biology, Emory University School of Medicine, 1510 Clifton Rd, Atlanta, GA 30322, United States. Electronic address:

Azaindole structural framework is an integral part of several biologically active natural and synthetic organic molecules; and several FDA approved drugs for various diseases. In the last decade, quite a number of literature reports appeared describing the pharmacology, biological activity and therapeutic applications of a variety of azaindole molecules. This prompted the organic and medicinal chemistry community to develop novel synthetic methods for various azaindoles and test them for a bioactivity against a variety of biological targets. Read More

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December 2020

Prostaglandin D: the end of a story or just the beginning?

Lancet Respir Med 2021 01 5;9(1):2-3. Epub 2020 Nov 5.

University of Groningen and University Medical Center Groningen, and Department of Molecular Pharmacology, University of Groningen, Groningen, Netherlands; Groningen Research Institute for Asthma and COPD, Groningen, Netherlands.

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January 2021

Effectiveness of fevipiprant in reducing exacerbations in patients with severe asthma (LUSTER-1 and LUSTER-2): two phase 3 randomised controlled trials.

Lancet Respir Med 2021 01 24;9(1):43-56. Epub 2020 Sep 24.

Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA.

Background: Fevipiprant, an oral antagonist of the prostaglandin D receptor 2, reduced sputum eosinophils and improved lung function in phase 2 trials of patients with asthma. We aimed to investigate whether fevipiprant reduces asthma exacerbations in patients with severe asthma.

Methods: LUSTER-1 and LUSTER-2 were two phase 3 randomised, double-blind, placebo-controlled, parallel-group, replicate 52-week studies; LUSTER-1 took place at 174 clinical sites in 25 countries and LUSTER 2 took place at 169 clinical sites in 19 countries. Read More

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January 2021

A Study of the Effect of Cyclosporine on Fevipiprant Pharmacokinetics and its Absolute Bioavailability Using an Intravenous Microdose Approach.

Drug Metab Dispos 2020 10 1;48(10):917-924. Epub 2020 Aug 1.

Novartis Institutes for Biomedical Research, Basel, Switzerland.

This drug-drug interaction study determined the effect of cyclosporine, an inhibitor of organic anion transporting polypeptide (OATP) 1B3 and P-gp, on the pharmacokinetics (PK) of fevipiprant, an oral, highly selective, competitive antagonist of the prostaglandin D receptor 2 and a substrate of the two transporters. The concomitant administration of an intravenous microdose of stable isotope-labeled fevipiprant provided the absolute bioavailability of fevipiprant as well as mechanistic insights into its PK and sensitivity to drug interactions. Liquid chromatography-mass spectrometry/mass spectrometry was used to measure plasma and urine concentrations. Read More

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October 2020

Revisiting Therapies for Atopic Dermatitis that Failed Clinical Trials.

Clin Drug Investig 2020 May;40(5):421-431

Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Multiple pathways contribute to the pathogenesis of atopic dermatitis (AD), and various targeted topical, biologic, and oral systemic agents have subsequently been developed. This review examines the mechanism of action and study designs of agents that have failed trials for AD to identify lessons that may shed light on reasons for their failure. Clinicaltrials. Read More

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Intersection of biology and therapeutics: type 2 targeted therapeutics for adult asthma.

Lancet 2020 02;395(10221):371-383

Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.

Asthma is a disease of reversible airflow obstruction characterised clinically by wheezing, shortness of breath, and coughing. Increases in airway type 2 cytokine activity, including interleukin-4 (IL-4), IL-5, and IL-13, are now established biological mechanisms in asthma. Inhaled corticosteroids have been the foundation for asthma treatment, in a large part because they decrease airway type 2 inflammation. Read More

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February 2020

New treatments for asthma: From the pathogenic role of prostaglandin D to the therapeutic effects of fevipiprant.

Pharmacol Res 2020 05 1;155:104490. Epub 2019 Nov 1.

Department of Medical and Surgical Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy. Electronic address:

Prostaglandin D (PGD) is a pleiotropic mediator, significantly involved in the pathogenesis of type 2 (T2) asthma because of its biologic actions exerted on both immune/inflammatory and airway structural cells. In particular, the pro-inflammatory and pro-remodelling effects of PGD are mainly mediated by stimulation of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). This receptor is the target of the oral competitive antagonist fevipiprant, which on the basis of recent phase II studies is emerging as a potential very promising anti-asthma drug. Read More

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Same Target, Different Therapeutic Outcomes: The Case of CAY10471 and Fevipiprant on CRTh2 Receptor in Treatment of Allergic Rhinitis and Asthma.

Comb Chem High Throughput Screen 2019 ;22(8):521-533

Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa.

Objective: Prostaglandin 2 (PGD2) mediated signalling of Chemoattractant Receptorhomologous molecule expressed on Th2 cells (CRTh2) receptor has been implicated in the recruitment of inflammatory cells. This explains the design of highly selective compounds with innate abilities to antagonize PGD2-CRTh2 interactions and prevent pro-inflammatory allergies such as rhinitis and uncontrolled asthma. The development of PGD2-competitive CRTh2 binders; CAY10471 and Fevipiprant represent remarkable therapeutic progress even though they elicit disparate pharmacological propensities despite utilizing the same binding pocket. Read More

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September 2020

Fevipiprant has a low risk of influencing co-medication pharmacokinetics: Impact on simvastatin and rosuvastatin in different SLCO1B1 genotypes.

Pulm Pharmacol Ther 2019 08 10;57:101809. Epub 2019 Jun 10.

Novartis Institutes for Biomedical Research, Basel, Switzerland. Electronic address:

Fevipiprant, a prostaglandin D receptor 2 antagonist, is in clinical development as a treatment for asthma. The goal of this study was to assess the potential of fevipiprant to cause drug-drug interactions (DDI) as a perpetrator, that is, by altering the pharmacokinetics (PK) of co-medications. In vitro drug interaction studies of clinically relevant drug metabolizing enzymes and transporters were conducted for fevipiprant and its acyl glucuronide (AG) metabolite. Read More

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New Targeted Therapies for Uncontrolled Asthma.

Jonathan Corren

J Allergy Clin Immunol Pract 2019 May - Jun;7(5):1394-1403

Departments of Medicine and Pediatrics, Division of Allergy and Clinical Immunology, David Geffen School of Medicine at UCLA, Los Angeles, Calif. Electronic address:

Mechanistic studies have improved our understanding of molecular and cellular components involved in asthma and our ability to treat severe patients. An mAb directed against IgE (omalizumab) has become an established add-on therapy for patients with uncontrolled allergic asthma and mAbs specific for IL-5 (reslizumab, mepolizumab), IL-5R (benralizumab), and IL-4R (dupilumab) have been approved as add-on treatments for uncontrolled eosinophilic (type 2) asthma. While these medications have proven highly effective, some patients with severe allergic and/or eosinophilic asthma, as well as most patients with severe non-type-2 disease, have poorly controlled disease. Read More

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Sustained exposure to prostaglandin D augments the contraction induced by acetylcholine via a DP receptor-mediated activation of p38 in bronchial smooth muscle of naive mice.

J Smooth Muscle Res 2019 ;55(0):1-13

Department of Physiology and Molecular Sciences, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.

Prostaglandin D (PGD), one of the key lipid mediators of allergic airway inflammation, is increased in the airways of asthmatics. However, the role of PGD in the pathogenesis of asthma is not fully understood. In the present study, effects of PGD on smooth muscle contractility of the airways were determined to elucidate its role in the development of airway hyperresponsiveness (AHR). Read More

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Fevipiprant, a selective prostaglandin D receptor 2 antagonist, inhibits human group 2 innate lymphoid cell aggregation and function.

J Allergy Clin Immunol 2019 06 28;143(6):2329-2333. Epub 2019 Feb 28.

MRC Human Immunology Unit and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom. Electronic address:

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DP antagonism reduces airway smooth muscle mass in asthma by decreasing eosinophilia and myofibroblast recruitment.

Sci Transl Med 2019 02;11(479)

University of Leicester, Leicester LE3 9QP, UK.

Increased airway smooth muscle mass, a feature of airway remodeling in asthma, is the strongest predictor of airflow limitation and contributes to asthma-associated morbidity and mortality. No current drug therapy for asthma is known to affect airway smooth muscle mass. Although there is increasing evidence that prostaglandin D type 2 receptor (DP) is expressed in airway structural and inflammatory cells, few studies have addressed the expression and function of DP in airway smooth muscle cells. Read More

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February 2019

Spotlight on fevipiprant and its potential in the treatment of asthma: evidence to date.

J Asthma Allergy 2019 3;12:1-5. Epub 2019 Jan 3.

Section of Pulmonary, Critical Care, and Sleep, Department of Medicine, Baylor College of Medicine, Houston, TX, USA,

Asthma is a heterogeneous disease, which may be classified into phenotypes and endotypes based on clinical characteristics and molecular mechanisms. The best described endotype of severe asthma is type 2 (T2)-high asthma, characterized by release of inflammatory cytokines by T helper 2 (T2) cells and type 2 innate lymphoid cells cells. Prostaglandin D2 contributes to T2 inflammation through binding of the G-protein-coupled receptor chemoattractant receptor-homologous molecule expressed on T2 cells (CRTH2). Read More

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January 2019

Prostaglandin D receptor antagonists in allergic disorders: safety, efficacy, and future perspectives.

Expert Opin Investig Drugs 2019 01 7;28(1):73-84. Epub 2018 Dec 7.

c Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI) , University of Naples Federico II , Naples , Italy.

Introduction: Prostaglandin D (PGD) is a major cyclooxygenase mediator that is synthesized by activated human mast cells and other immune cells. The biological effects of PGD are mediated by D-prostanoid (DP), DP (CRTH2) and thromboxane prostanoid (TP) receptors that are expressed on several immune and non-immune cells involved in allergic inflammation. PGD exerts various proinflammatory effects relevant to the pathophysiology of allergic disorders. Read More

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January 2019

An evaluation of fevipiprant for the treatment of asthma: a promising new therapy?

Expert Opin Pharmacother 2018 Dec 3;19(18):2087-2093. Epub 2018 Nov 3.

c Division of Pulmonary, Allergy, and Sleep Medicine , Mayo Clinic , Jacksonville , Florida , USA.

Introduction: Asthma is a heterogeneous disease characterized by chronic airway inflammation that affects more than 230 million people worldwide. Current guidelines recommend an escalating stepwise decision model for the management of asthma. However, disease control continues to be a challenge, particularly in patients with severe asthma. Read More

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December 2018

Structures of the Human PGD Receptor CRTH2 Reveal Novel Mechanisms for Ligand Recognition.

Mol Cell 2018 10 13;72(1):48-59.e4. Epub 2018 Sep 13.

Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. Electronic address:

The signaling of prostaglandin D (PGD) through G-protein-coupled receptor (GPCR) CRTH2 is a major pathway in type 2 inflammation. Compelling evidence suggests the therapeutic benefits of blocking CRTH2 signaling in many inflammatory disorders. Currently, a number of CRTH2 antagonists are under clinical investigation, and one compound, fevipiprant, has advanced to phase 3 clinical trials for asthma. Read More

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October 2018

Fevipiprant in the treatment of asthma.

Expert Opin Investig Drugs 2018 Feb 30;27(2):199-207. Epub 2018 Jan 30.

a Institute for Lung Health, NIHR Leicester Biomedical Research Centre, Department of Infection, Immunity & Inflammation , University of Leicester and University Hospitals of Leicester NHS Trust , Leicester , UK.

Introduction: Asthma is common and in many, particularly those with more severe disease, there remains a substantial unmet need. Success with biologics targeting eosinophilic inflammation underscore the value of treating inflammation in asthma beyond corticosteroids. Fevipiprant (QAW039) is an oral treatment for asthma. Read More

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February 2018

New and Anticipated Therapies for Severe Asthma.

J Allergy Clin Immunol Pract 2017 Sep - Oct;5(5S):S15-S24

UW Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.

Asthma is frequently undertreated, resulting in a relatively high prevalence of patients with uncontrolled disease, characterized by the presence of symptoms and risk of adverse outcomes. Patients with uncontrolled asthma have a higher risk of morbidity and mortality, underscoring the importance of identifying uncontrolled disease and modifying management plans to improve control. Several assessment tools exist to evaluate control with various cutoff points and measures, but these tools do not reliably correlate with physiological measures and should be considered a supplement to physiological tests. Read More

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

Eur Respir J 2017 08 24;50(2). Epub 2017 Aug 24.

Internal Medicine/Allergy, Creighton University, Omaha, NE, USA.

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. Read More

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New Anti-Eosinophil Drugs for Asthma and COPD: Targeting the Trait!

Chest 2017 12 2;152(6):1276-1282. Epub 2017 Jun 2.

Medical Centre Leeuwarden, Leeuwarden, The Netherlands.

Asthma and COPD are prevalent chronic inflammatory airway diseases that are responsible for a large global disease burden. Both diseases are complex and heterogeneous, and they are increasingly recognized as overlapping syndromes that may share similar pathophysiologic mechanisms and treatable traits. Eosinophilic airway inflammation is considered the most influential treatable trait of chronic airway disease, and over the last decade, several monoclonal antibodies and small molecule therapies have been developed to target this trait. Read More

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December 2017

Discovery of Fevipiprant (NVP-QAW039), a Potent and Selective DP Receptor Antagonist for Treatment of Asthma.

ACS Med Chem Lett 2017 May 25;8(5):582-586. Epub 2017 Apr 25.

Novartis Institutes for Biomedical Research, Horsham Research Centre, Wimblehurst Road, Horsham, West Sussex RH12 5AB, United Kingdom.

Further optimization of an initial DP receptor antagonist clinical candidate NVP-QAV680 led to the discovery of a follow-up molecule 2-(2-methyl-1-(4-(methylsulfonyl)-2-(trifluoromethyl)benzyl)-1-pyrrolo[2,3-]pyridin-3-yl)acetic acid (compound , NVP-QAW039, fevipiprant), which exhibits improved potency on human eosinophils and Th2 cells, together with a longer receptor residence time, and is currently in clinical trials for severe asthma. Read More

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Absorption, Distribution, Metabolism, and Excretion of the Oral Prostaglandin D2 Receptor 2 Antagonist Fevipiprant (QAW039) in Healthy Volunteers and In Vitro.

Drug Metab Dispos 2017 07 25;45(7):817-825. Epub 2017 Apr 25.

Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland (D.P., H.M.W., Y.J., V.J.E., U.G., P.E., R.W., F.E., G.C.); PRA International, Early Development Services, Zuidlaren, the Netherlands (J.J.v.L.).

Fevipiprant is a novel oral prostaglandin D receptor 2 (DP; also known as CRTh2) antagonist, which is currently in development for the treatment of severe asthma and atopic dermatitis. We investigated the absorption, distribution, metabolism, and excretion properties of fevipiprant in healthy subjects after a single 200-mg oral dose of [C]-radiolabeled fevipiprant. Fevipiprant and metabolites were analyzed by liquid chromatography coupled to tandem mass spectrometry and radioactivity measurements, and mechanistic in vitro studies were performed to investigate clearance pathways and covalent plasma protein binding. Read More

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Data on the oral CRTh2 antagonist QAW039 (fevipiprant) in patients with uncontrolled allergic asthma.

Data Brief 2016 Dec 29;9:199-205. Epub 2016 Aug 29.

INSAF, Respiratory Research Institute GmbH, Wiesbaden, Germany.

This article contains data on clinical endpoints (Peak Flow Expiratory Rate, fractional exhaled nitric oxide and total IgE serum levels) and plasma pharmacokinetic parameters concerning the use of the oral CRTh2 antagonist QAW039 (fevipiprant) in mild to moderate asthma patients. Information on experimental design and methods on how this data was obtained is also described. Further interpretation and discussion of this data can be found in the article "The oral CRTh2 antagonist QAW039 (fevipiprant): a phase II study in uncontrolled allergic asthma" (Erpenbeck et al. Read More

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December 2016