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

Brightling, Christopher E.; Gaga, Mina; Inoue, Hiromasa; Li, Jing; Máspero, Jorge; Wenzel, Sally E.; Maitra, Samopriyo; Lawrence, David; Brockhaus, Florian; Lehmann, Thomas; Brindicci, Caterina; Knorr, Barbara; Bleecker, Eugene R.

doi:10.1016/s2213-2600(20)30412-4

Cited by 77 publications

(73 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, data on exhaled nitric oxide (FeNO) levels and other biomarkers were not captured. The pre-bronchodilator FEV 1 values in ZEAL were similar to the findings from the LUSTER studies [15] (LUSTER-1: NCT02555683; LUSTER-2 NCT02563067) conducted in patients with severe asthma. Increased asthma exacerbation rates predict increased response to biologic therapy [16] (anti-IL-5 etc.…”

Section: Discussionsupporting

confidence: 77%

“…This would be another reason why DP 2 antagonists may exhibit a greater response in patients with severe and eosinophilic asthma. The 52-week LUSTER [15] studies (LUSTER-1: NCT02555683; LUSTER-2 NCT02563067) did include patients with more severe asthma and prior exacerbations, but these studies did not show a significant effect with fevipiprant on exacerbation rate and lung function.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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)

et al. 2021

Self Cite

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

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)

et al. 2021

Self Cite

View full text Add to dashboard Cite

“…Luster 1 (CQAW039A2307, abbreviated as A2307, clinicaltrials. org: NCT02555683) and Luster 2 (CQAW039A2314, abbreviated as A2314, clinicaltrials.org: NCT02563067) were two Phase III studies investigating the efficacy and safety of fevipiprant in asthma patients who are on medium or high dose of inhaled corticosteroids plus 1 or 2 additional controllers [10,11]. Sparse pharmacokinetic (PK) samples were collected in these studies to characterize the exposure of fevipiprant in this patient population.…”

Section: Population Pharmacokinetic Analysis Of Fevipiprant In Healthmentioning

confidence: 99%

Population Pharmacokinetic Analysis of Fevipiprant in Healthy Subjects and Asthma Patients using a Tukey’s g-and-h Distribution

Wang¹,

Bartels

Kulkarni

et al. 2021

Drug Res (Stuttg)

View full text Add to dashboard Cite

Aim The objective of this analysis was to characterize the population pharmacokinetics (PK) of fevipiprant in asthma patients and to evaluate the effect of baseline covariates on the PK of fevipiprant. Methods PK data from 1281 healthy subjects or asthma patients were available after single or once daily dosing of fevipiprant. Population PK analysis was conducted to describe fevipiprant plasma concentration data using a non-linear mixed effect modeling approach. Results Fevipiprant PK was described by a two-compartment model with first-order absorption and first-order elimination. Exploration of fevipiprant PK in the population from the phase III studies revealed an over-dispersed and skewed distribution. This unusual distribution was described using Tukey’s g-and-h distribution (TGH) on the between-subject variability of apparent clearance (CL/F). The model identified a significant impact of disease status on CL/F, with the value in healthy subjects being 62% higher than that in asthma patients. Bodyweight, age and renal function showed statistically significant impact on fevipiprant clearance; however, compared with a typical asthma patient, the simulated difference in steady-state exposure was at most 16%. Conclusion Fevipiprant PK was described by a two-compartment model with first-order absorption and first-order elimination. The TGH distribution was appropriate to describe the over-dispersed and skewed PK data as observed in the current studies. Asthma patients had approximately 37% higher exposure than healthy subjects did. Other covariates changed exposure by at most 16%.

show abstract

“…Dual DP/CRTH2 antagonist (AMG853) treatment for 12 weeks failed to show clinical effectiveness in patients with moderate to severe asthma [ 155 ]. Another CRTH2 receptor antagonist, fevipiprant, for 12 weeks, has shown to improve clinical and physiological parameters and to reduce airway eosinophils in patients with moderate-severe asthma [ 154 ], and it reduced asthma exacerbations moderately, but not significantly, in 52-week phase 3 trials in patients with severe asthma [ 156 ].…”

Section: Monoclonal Antibodies and Treatment Of Airway Diseasesmentioning

confidence: 99%

Monoclonal Antibodies and Airway Diseases

Lyly

Laulajainen‐Hongisto

Gevaert

et al. 2020

IJMS

View full text Add to dashboard Cite

Monoclonal antibodies, biologics, are a relatively new treatment option for severe chronic airway diseases, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS). In this review, we focus on the physiological and pathomechanisms of monoclonal antibodies, and we present recent study results regarding their use as a therapeutic option against severe airway diseases. Airway mucosa acts as a relative barrier, modulating antigenic stimulation and responding to environmental pathogen exposure with a specific, self-limited response. In severe asthma and/or CRS, genome–environmental interactions lead to dysbiosis, aggravated inflammation, and disease. In healthy conditions, single or combined type 1, 2, and 3 immunological response pathways are invoked, generating cytokine, chemokine, innate cellular and T helper (Th) responses to eliminate viruses, helminths, and extracellular bacteria/fungi, correspondingly. Although the pathomechanisms are not fully known, the majority of severe airway diseases are related to type 2 high inflammation. Type 2 cytokines interleukins (IL) 4, 5, and 13, are orchestrated by innate lymphoid cell (ILC) and Th subsets leading to eosinophilia, immunoglobulin E (IgE) responses, and permanently impaired airway damage. Monoclonal antibodies can bind or block key parts of these inflammatory pathways, resulting in less inflammation and improved disease control.

show abstract

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

Cited by 77 publications

References 40 publications

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)

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)

Population Pharmacokinetic Analysis of Fevipiprant in Healthy Subjects and Asthma Patients using a Tukey’s g-and-h Distribution

Monoclonal Antibodies and Airway Diseases

Contact Info

Product

Resources

About