Safety and Efficacy Of ARRY-502, a Potent, Selective, Oral CRTh2 Antagonist, In Patients With Mild To Moderate Th2-Driven Asthma

Wenzel, Sally E.; Hopkins, Robert W.; Saunders, Michael D.; Chantry, David; Anderson, Lisa R.; Aitchison, Roger; Eberhardt, Christine; Bell, Stacie; Cole, Jeremy; Wolfe, James; Spector, Sheldon L.; Sher, Lawrence; Kerwin, Edward

doi:10.1016/j.jaci.2013.12.037

Cited by 16 publications

(19 citation statements)

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“…Another DP2 antagonist, ARRY-502, improved one second-forced expiratory volume (FEV 1 ) results as well as symptom-related quality of life of patients with asthma relative to control patients. This effect was greater in patients with elevated Th2-associated biomarkers [135]. Treatment with AZD1981, a DP2 receptor antagonist, showed improvements in the asthma control questionnaire score as well as FEV 1 in patients with allergic asthma after four weeks [136].…”

Section: Asthmamentioning

confidence: 90%

The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

Lee

Kim

2020

IJMS

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Prostaglandins (PGs) are a family of lipid compounds that are derived from arachidonic acid via the cyclooxygenase pathway, and consist of PGD 2 , PGI 2 , PGE 2 , PGF 2 , and thromboxane B 2 . PGs signal through G-protein coupled receptors, and individual PGs affect allergic inflammation through different mechanisms according to the receptors with which they are associated. In this review article, we have focused on the metabolism of the cyclooxygenase pathway, and the distinct biological effect of each PG type on various cell types involved in allergic airway diseases, including asthma, allergic rhinitis, nasal polyposis, and aspirin-exacerbated respiratory disease.

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Section: Asthmamentioning

confidence: 90%

The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

Lee

Kim

2020

IJMS

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“…In the post hoc analysis of patients with blood eosinophils ≥250/μL, the eosinophilic subgroup showed greater improvement in FEV 1 (mean increase of 220 mL compared to placebo; P = 0.005), particularly in a younger population (mean increase of 355 mL in subjects ≤40 years old compared to placebo; P = 0.007) [ 32 ]. Similarly, ARRY-502 showed slightly improved FEV 1 (3.9%; P = 0.02), Asthma Control Questionaaire-7 ( P < 0.001), beta-agonist use ( P < 0.001), and symptom free days ( P = 0.07) compared to placebo in patients with elevated Th2 associated biomarkers [ 34 ]. BI 671800 has varying results, ranging from no significant difference to small significant improvement in FEV 1 and/or asthma control scores depending on the study [ 35 , 36 ].…”

Section: Novel Targets In T2-hi Asthmamentioning

confidence: 99%

“…AMG853 and setipiprant have been discontinued due to poor efficacy [ 40 , 41 ]. Of note, the studies that stratified asthma by phenotype found greater efficacy in subgroups with elevated serum eosinophils [ 32 , 39 ] and FeNO [ 34 ], which may explain why other trials with CRTH2 antagonists that did not stratify by T2 inflammation did not yield positive results.…”

Section: Novel Targets In T2-hi Asthmamentioning

confidence: 99%

Potential new targets for drug development in severe asthma

Zhu

Ciaccio

Casale

2018

World Allergy Organization Journal

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In recent years there has been increasing recognition of varying asthma phenotypes that impact treatment response. This has led to the development of biological therapies targeting specific immune cells and cytokines in the inflammatory cascade. Currently, there are two primary asthma phenotypes, Type 2 hi and Type 2 lo, which are defined by eosinophilic and neutrophilic/pauci- granulocytic pattern of inflammation respectively. Most biologics focus on Type 2 hi asthma, including all four biologics approved for treatment of uncontrolled asthma in the United States — omalizumab, mepolizumab, reslizumab, and benralizumab. Potential new targets for drug development are being investigated, such as IL-13, IL-4α receptor, CRTH2, TSLP, IL-25, IL-13, IL-17A receptor, and CXCR2/IL-8. This review will discuss the role of these molecules on the inflammatory response in uncontrolled asthma and the emerging biologics that address them. Through the delineation of distinct immunological mechanisms in severe asthma, targeted biologics are promising new therapies that have the potential to improve asthma control and quality of life.

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“…Indeed, when these study participants are analyzed separately, the results are more impressive. For example, there were significantly greater increases in FEV 1 in subgroups with: elevated serum eosinophils [10], positive skin prick tests [11], and raised FeNO [12].The choice of end points assessed may also be painting an unduly negative picture of CRTH2 antagonist efficacy in clinical trials of asthma. In particular, no trial to date has been powered to detect an effect on asthma exacerbations, an outcome responsible for the majority of morbidity and mortality in asthma and around half the health-care costs.…”

Section: Evidence To Datementioning

confidence: 99%