fevipiprant (QAW039) / Novartis - LARVOL DELTA

Innovative approaches to eczema treatment: A review of Fevipiprant and its potential as a new therapeutic agent. (PubMed, Prostaglandins Other Lipid Mediat) - "Novartis has taken advantage of this stat for comp… given the scarcity of effective therapies for paediatric atopic dermatitis in Japan. Exploring Fevipiprant from the Efficacy Perspective is also required because it will impact how it will enter clinical practice in therapy of eczema in the future."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pediatrics

Prostaglandin D2 receptor 2 downstream signaling and modulation of type 2 innate lymphoid cells from patients with asthma. (PubMed, PLoS One) - "ILC2s were stimulated with PGD2 and four PGD2 metabolites (Δ12-PGJ2, Δ12-PGD2, 15-deoxyΔ12,14-PGD2, 9α,11β-PGF2) with or without the selective DP2 antagonist fevipiprant...Furthermore, PGD2 and metabolites showed distinct profiles in ILC2 activation. Overall, these results expand our understanding of DP2 initiated ILC2 activity."

IO biomarker • Journal • Allergy • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • ADGRG1 • ARG2 • CD69 • DDIT4 • DUSP4 • DUSP6 • ETV1 • IL13 • IL5 • LAYN • PTGDR • PTGDR2 • SLC43A2 • SPRED2

Transcriptomic Characterization of Type 2 Innate Lymphoid Cells From Asthma Patients in Response to Prostaglandin D2 Metabolites (ATS 2024) - "Pathway analysis underlines the pro-inflammatory effects of PGD2 metabolite-induced immune response in ILC2s as well as the anti-inflammatory effects of DP2 inhibition via fevipiprant. Overall, our results further our understanding of DP2 initiated ILC2 activity."

Clinical • IO biomarker • Allergy • Asthma • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • ADGRG1 • ARG2 • CD69 • DDIT4 • DUSP4 • DUSP6 • ETV1 • IL13 • IL5 • LAYN • PTGDR • SLC43A2 • SPRED2

Transcriptomic characterization of type 2 innate lymphoid cells from asthma patients in response to prostaglandin D2 metabolites (ERS 2023) - "ILC2s were stimulated with PGD2 and four PGD2 metabolites (Δ12PGJ2, Δ12PGD2, 15-deoxyΔ12,14PGD2, 9α,11βPGF2) with or without the selective DP2 antagonist fevipiprant...Elevated HPGDS would catalyze further PGD2 synthesis and thus increase inflammation. Our results further our understanding of DP2 initiated ILC2 activity.; Cell and molecular biology; Epidemiology; General respiratory patient care; Physiology; Respiratory intensive care"

Clinical • Allergy • Asthma • Critical care • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • DDIT4 • IL13 • IL5 • ITGB2 • LAYN • PTGDR

"Establishing the Safe Space via Physiologically Based #Biopharmaceutics Modeling. Case Study: #Fevipiprant/QAW039 | Alexandros Kourentas; Martin Mueller-Zsigmondy @Novartis @Merck | https://t.co/MLmmeZ88vP #PBBM #GastroPlus #SafeSpace #AAPSJ @AAPSComms" (@theaapsjournal)

Establishing the Safe Space via Physiologically Based Biopharmaceutics Modeling. Case Study: Fevipiprant/QAW039. (PubMed, AAPS J) - "The dissolution profile of the 450 mg commercial scale batch was within a dissolution region where bioequivalence is anticipated, not near an edge of failure for dissolution, providing additional confidence to the proposed acceptance criteria. Thus, the safe space allowed for a wider than 10% dissolution difference for bioequivalent batches, superseding f similarity analyses."

Journal • Gastrointestinal Disorder

Recent developments in the management of severe asthma. (PubMed, Breathe (Sheff)) - "Fevipiprant is unlikely to be implemented as a future treatment for severe asthma, while tezepelumab may be a future treatment option for patients with severe asthma with and without eosinophilic inflammation https://bit.ly/3KE1BH4."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Assessing the Anti-Inflammatory Effects of an Orally Dosed Enzymatically Liberated Fish Oil in a House Dust Model of Allergic Asthma. (PubMed, Biomedicines) - "The CRTH2 antagonist fevipiprant showed an anti-inflammatory profile similar to that of OmeGo. OmeGo has the potential to be a pragmatic, cost-effective co-treatment for less severe forms of eosinophilic asthma. Proof-of-concept studies are planned."

Journal • Allergy • Asthma • Eosinophilia • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL5

Commercial scale transfer of a twin-screw melt granulation process for high drug load fevipiprant tablets. (PubMed, Drug Dev Ind Pharm) - "Compression of the six final blends (∼300 kg) showed no impact of varied granulation and compression process conditions on both CQAs. A near-infrared spectroscopy method was validated to determine content uniformity, assay, identity, and to predict CQAs on uncoated tablets in preparation for a real time release testing (RTRT) of future batches."

Journal

Efficacy and Safety of Fevipiprant in Asthma: A Review and Meta-Analysis. (PubMed, Cureus) - "It significantly increased pre-and post-bronchodilator FEV1 and improved ACQ scores in treated patients. The benefits, though statistically significant, failed to translate into clinical importance."

Clinical • Journal • Retrospective data • Review • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Chemoattractant-Receptor Homologous Molecule on Th2 Cells (CRTH2) Regulates Neutrophilic Inflammation in the Lung (ATS 2022) - "These studies reveal that CRTH2 is functionally expressed on murine neutrophils after extravasation into the lung. While previously considered a mediator of type 2 immune responses (e.g. in allergic and eosinophilic asthma), our findings now implicate CRTH2 in neutrophilic inflammation as well."

Allergy • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • CASP3 • ELANE

Pharmacological evaluation of the effects of enzymatically liberated fish oil on eosinophilic inflammation in animal models. (PubMed, Biotechnol Appl Biochem) - "The CRTH2 antagonist fevipiprant showed a similar eosinophilic inhibitory profile to OmeGo...OmeGo therefore combines a consistent anti-eosinophilic action with the known anti-inflammatory effects of PUFAs. Proof-of-concept studies in asthma are warranted."

Journal • Preclinical • Allergy • Asthma • Eosinophilia • Eosinophilic Esophagitis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases

Fevipiprant in CRSwNP and comorbid asthma: Wrong target population or wrong PGD receptor? (PubMed, J Allergy Clin Immunol) - No abstract available

Journal • Asthma • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Sinusitis

Role of prostaglandin D2 receptors in the pathogenesis of abdominal aortic aneurysm formation. (PubMed, Clin Sci (Lond)) - " Treatment with selective antagonists of DP1 (laropiprant) or DP2 (fevipiprant) protected against AAA formation, in conjunction with reduced elastin degradation and aortic inflammatory responses. In conclusion, PGD2 signaling contributes to AAA formation in mice, suggesting that antagonists of DP receptors, which have been extensively tested in allergic and lung diseases, may be promising candidates to ameliorate AAA."

Journal • Cardiovascular • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • PTGDR

Phase 3b randomized controlled trial of fevipiprant in patients with nasal polyposis with asthma (THUNDER). (PubMed, J Allergy Clin Immunol) - "THUNDER provided no evidence of a role for fevipiprant in the treatment of patients with CRSwNP and asthma; future studies may establish a role for other DP antagonists, specifically in patients with aspirin-exacerbated respiratory disease."

Journal • P3 data • Asthma • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Sinusitis

Long-term safety and exploratory efficacy of fevipiprant in patients with inadequately controlled asthma: the SPIRIT randomised clinical trial. (PubMed, Respir Res) - P3 | "In patients with uncontrolled asthma, the addition of fevipiprant had a favourable long-term safety profile."

Clinical • Journal • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Fevipiprant (QAW039) does not affect the pharmacokinetics of zidovudine, its glucuronide, and penicillin G via inhibition of UGT2B7 and/or OAT3. (PubMed, Pulm Pharmacol Ther) - No abstract available

Journal • PK/PD data

Prostaglandin D metabolites activate asthmatic patient-derived type 2 innate lymphoid cells and eosinophils via the DP receptor. (PubMed, Respir Res) - "Prostaglandin D metabolites initiate ILC2 migration and IL-5 and IL-13 cytokine secretion in a DP dependent manner. Our data indicate that metabolites may be important for in vivo eosinophil activation and ILC2 migration and to a lesser extent for ILC2 cytokine secretion."

Clinical • Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL13 • IL5

[VIRTUAL] Use and reporting of health related quality of life questionnaires in severe asthma clinical trials (ERS 2021) - "In order to increase the use of asthma HRQoL questionnaires in RCTs of severe asthma treatments, the barriers to their use must first be understood. At present the patients’ perspective is underrepresented in RCTs of biologics, fevipiprant and bronchial thermoplasty for severe asthma."

Clinical • HEOR • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Use of Health Related Quality of Life in Clinical Trials for Severe Asthma: A Systematic Review. (PubMed, J Asthma Allergy) - "In order to increase the use of asthma HRQoL questionnaires in RCTs of severe asthma treatments, the drivers and barriers to their use must first be understood. At present, the patients' perspective is underrepresented in RCTs of biologics, fevipiprant and bronchial thermoplasty for severe asthma."

Clinical • HEOR • Journal • Review • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Efficacy and Safety of Prostaglandin D2 Receptor 2 Antagonism with Fevipiprant for Patients with Asthma: a Systematic Review and Meta-analysis of Randomized Controlled Trials. (PubMed, Curr Allergy Asthma Rep) - "Fevipiprant could safely improve asthma outcomes compared to placebo. However, most of the differences didn't reach the minimal clinically important difference (MCID), thus the clinical benefits remained to be confirmed."

Journal • Retrospective data • Review • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • PTGDR

The Roles of Type 2 Cytotoxic T Cells in Inflammation, Tissue Remodeling, and Prostaglandin (PG) D Production Are Attenuated by PGD Receptor 2 Antagonism. (PubMed, J Immunol) - "Using fevipiprant, a specific DP2 antagonist, we demonstrated that competitive inhibition of DP2 not only completely blocked the cell migration, adhesion, proinflammatory cytokine production, and survival of Tc2 cells triggered by PGD but also attenuated the tissue-remodeling effects and autocrine/paracrine PGD production in Tc2 induced by PGD and other stimulators. These findings further confirmed the anti-inflammatory effect of fevipiprant and provided a better understanding of the role of Tc2 cells in the pathogenesis of asthma."

Journal • Asthma • Eosinophilia • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

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). (PubMed, EClinicalMedicine) - P3 | "The ZEAL studies did not demonstrate significant improvement in lung function or other clinical outcomes. These results suggest that DP receptor inhibition with fevipiprant is not effective in the studied patient population."

Clinical • Journal • P3 data • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] Late Breaking Abstract - LUSTER-1 and -2: randomised controlled trials of fevipiprant in severe asthma (ERS 2020) - "No safety or tolerability issues were noted. Conclusion While not statistically significant, there were modest reductions in exacerbations and improvements in lung function for the higher dose of fevipiprant in both trials."

Clinical • Late-breaking abstract • Asthma • Respiratory Diseases

The pharmacology of the prostaglandin D receptor 2 (DP) receptor antagonist, fevipiprant. (PubMed, Pulm Pharmacol Ther) - "Phase II clinical trials of fevipiprant showed reduction in sputum eosinophilia, as well as improvement in lung function, symptoms and quality of life in patients with asthma. While fevipiprant reached the most advanced state of development to date of an oral DP receptor antagonist in a worldwide Phase III clinical trial programme, the demonstrated efficacy did not support further clinical development in asthma."

Journal • Review • Asthma • Eosinophilia • Immunology • Inflammation • Respiratory Diseases • CD8