Late Breaking Abstract - Multiple ascending dose study of the inhaled IL-4Ra antagonist, AZD1402/PRS-060, in mild asthmatics demonstrates robust FeNO reduction and a promising clinical profile for the treatment of asthma

Bruns, Ingmar; Fitzgerald, Mary; Mensing, George; Tsung, Mei; Pardali, Katerina; Philip, Gardiner; Kis, Dávid; Axelsson, L.; Olsson, Marita; Ghobadi, Cyrus; Walsh, O M; Mclendon, Kristi; Farinola, Nicholas; Hatchuel, Lara; Coynel, David

doi:10.1183/13993003.congress-2019.pa3709

Cited by 3 publications

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“…Study results for seven RCTs [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ] were retrieved from ClinicalTrials.gov, results for five RCTs [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ] were published in full text articles, and data for two RCTs [ 40 , 41 , 42 , 43 ] were obtained through the European Union (EU) Clinical Trial Register. Results for two RCTs [ 44 , 45 , 46 , 47 ] were available only from conference abstracts or posters, data for one RCT [ 48 , 49 , 50 ] were retrieved from both the EU Clinical Trial Register and abstract, and for another RCT, they were retrieved from both ClinicalTrials.gov and the abstract [ 51 , 52 ]. Results for one RCT [ 53 , 54 ] were provided on the pharmaceutical company’s website.…”

Section: Resultsmentioning

confidence: 99%

Investigational Treatments in Phase I and II Clinical Trials: A Systematic Review in Asthma

et al. 2022

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Inhaled corticosteroids (ICS) remain the mainstay of asthma treatment, along with bronchodilators serving as control agents in combination with ICS or reliever therapy. Although current pharmacological treatments improve symptom control, health status, and the frequency and severity of exacerbations, they do not really change the natural course of asthma, including disease remission. Considering the highly heterogeneous nature of asthma, there is a strong need for innovative medications that selectively target components of the inflammatory cascade. The aim of this review was to systematically assess current investigational agents in Phase I and II randomised controlled trials (RCTs) over the last five years. Sixteen classes of novel therapeutic options were identified from 19 RCTs. Drugs belonging to different classes, such as the anti-interleukin (IL)-4Rα inhibitors, anti-IL-5 monoclonal antibodies (mAbs), anti-IL-17A mAbs, anti-thymic stromal lymphopoietin (TSLP) mAbs, epithelial sodium channel (ENaC) inhibitors, bifunctional M3 receptor muscarinic antagonists/β2-adrenoceptor agonists (MABAs), and anti-Fel d 1 mAbs, were found to be effective in the treatment of asthma, with lung function being the main assessed outcome across the RCTs. Several novel investigational molecules, particularly biologics, seem promising as future disease-modifying agents; nevertheless, further larger studies are required to confirm positive results from Phase I and II RCTs.

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Section: Resultsmentioning

confidence: 99%

Investigational Treatments in Phase I and II Clinical Trials: A Systematic Review in Asthma

et al. 2022

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“…Pulmonary delivery of biologics is an attractive non-invasive route of administration for the treatment of respiratory diseases [76][77][78][79], such as asthma [80][81][82][83][84], cystic fibrosis [85,86], alpha-1 antitrypsin deficiency (AATP) [87,88], pulmonary alveolar proteinosis (PAP) [89,90], lung cancer [91,92], and SARS-CoV-2 [93][94][95]. Pulmonary delivery of biologics is also an alternative route for administering biologics for the treatment of non-respiratory systemic diseases, including diabetes mellitus [96][97][98], anaemia [99], and multiple sclerosis [100].…”

Section: Pulmonary Delivery Of Aerosol Biologicsmentioning

confidence: 99%

“…Pulmonary delivery of biologics is also an alternative route for administering biologics for the treatment of non-respiratory systemic diseases, including diabetes mellitus [96][97][98], anaemia [99], and multiple sclerosis [100]. The development of inhalation biologics, and design of methods of inhalation technology are outside the scope of this manuscript, but excellent information can be found in references [76][77][78][79]. Table 2 shows preclinical trials of aerosol biologics for the treatment of respiratory diseases, and non-respiratory systemic diseases.…”

Section: Pulmonary Delivery Of Aerosol Biologicsmentioning

confidence: 99%

“…However, despite the beneficial effects of pulmonary delivery of biologics, it requires innovative biotechnology to develop biologics, and inhaler devices to propel the biologics to the tracheobronchial tree, and lung parenchyma [76][77][78][79]. Furthermore, there are anatomical, physiological, and immunological factors that affect the pharmacodynamics, and biotherapeutic efficacy, and safety of inhaled biologics [102].…”

Section: Pulmonary Delivery Of Aerosol Biologicsmentioning

confidence: 99%

“…Furthermore, there are anatomical, physiological, and immunological factors that affect the pharmacodynamics, and biotherapeutic efficacy, and safety of inhaled biologics [102]. The other obstacle is the formulation of biologics for delivery into the lungs [78,79,103]. Three methods have been applied to modify the structure, aerodynamic diameter (Dae), shape, hydroscopicity, and density of biologics to enhance their absorption through the mucociliary blanket, pharmacokinetics, and bioavailability [104,105].…”

Section: Pulmonary Delivery Of Aerosol Biologicsmentioning

confidence: 99%

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Aerosol Biologics for the Treatment of Eosinophilic Asthma

Syabbalo¹

2022

JTCS

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Asthma is a heterogeneous chronic airway disease comprising of distinct phenotypes characterized by different immunopathophysiologic pathways, clinical features, disease severity, and response to treatment. The phenotypes of asthma include eosinophilic, neutrophilic, mixed cellularity, and paucigranulocytic asthma. Eosinophilic asthma is principally a T helper type 2 (Th2)-mediated airway disease. However, several other immune and structural cells secrete the cytokines implicated in the pathogenesis of eosinophilic asthma. Innate type 2 lymphoid cells, mast cells, basophils, and eosinophils secrete Th2 cytokines, such as interleukin-4 (IL-4), IL-13, and IL-5. Additionally, airway epithelial cells produce alarmin cytokines, including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). Alarmins are the key initiators of allergic inflammation at the sentinel mucosal surfaces. Innovative biotherapeutic research has led to the discovery of monoclonal antibodies which target and inhibit the immunopathological effects of the cytokines involved in the pathogenesis of eosinophilic asthma. Parenteral biologics targeting the inciting interleukins, include mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5Rα), dupilumab (anti-4Rα), and tezelizumab (anti-TSLP). They have been shown to significantly reduce annualized exacerbation rates, improve asthma control, lung function, and quality of life. Currently, there are no pulmonary delivered aerosol biologics for topical treatment of asthma. CSJ117 is a potent neutralizing antibody Fab fragment against TSLP, formulated as a PulmoSol TM engineered powder, and is delivered to the lungs by a dry powder inhaler. Phase 2 placebo-controlled clinical trial evaluated the efficacy and safety of CSJ117. CSJ117 delivered as an inhaler attenuated the late asthmatic response (LAR), and the early asthmatic response (EAR) after allergen inhalation challenge (AIC) at day 84 of treatment. The maximum decrease in FVE1 from pre-AIC were significantly lower in the CSJ117 group compared to placebo (P = 029), during LAR. CSJ117 also significantly reduced fractional exhaled nitric oxide before AIC at day 83; and significantly reduced the allergen-induced increase in % sputum eosinophil count. Pulmonary delivery of biologics directly to the airway mucosal surface has several advantages over parenteral routes, particularly in treating airway diseases such as asthma. Inhaler delivered biologics, such as CSJ117 are innovative and attractive methods of future precision treatment of asthma, and other respiratory diseases.

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Recent advances predict a bright future for nebulizers

Troy

Vleet

Tashkin

2023

Current Opinion in Pulmonary Medicine

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Purpose of reviewWith the improvement in device technology and delivery methods of inhaled medications, along with development of novel compounds and recognition of the importance of personalized approach in the management of chronic airway diseases, nebulizers have not only maintained their place in the treatment hierarchy of airway disease but have also proven a vital platform for the development of new classes of drugs. Recent findingsThis short review explores recent advances in nebulized drug delivery in chronic obstructive pulmonary disease and other chronic airway diseases, emphasizing the progress in nebulizer technology, physiologic advantages of nebulized drug delivery and the high versatility of currently available and developing nebulizer-delivered pharmacotherapies. SummaryVersatility and efficiency of nebulizers allows for a broad spectrum of existing and novel therapies to be clinically studied, facilitating the progress in phenotype-targeted pharmacotherapies in the management of chronic airway diseases Keywords aerosolized drugs, chronic airway disease, chronic obstructive pulmonary disease, nebulizer, novel pharmacotherapies, phenotype && ,8,9]. Here, we discuss recent advances in nebulized drug delivery in COPD and other airway diseases with an emphasis on the advantages of nebulizer-delivered approaches compared with hand-held inhalers.

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Late Breaking Abstract - Multiple ascending dose study of the inhaled IL-4Ra antagonist, AZD1402/PRS-060, in mild asthmatics demonstrates robust FeNO reduction and a promising clinical profile for the treatment of asthma

Cited by 3 publications

References 0 publications

Investigational Treatments in Phase I and II Clinical Trials: A Systematic Review in Asthma

Investigational Treatments in Phase I and II Clinical Trials: A Systematic Review in Asthma

Aerosol Biologics for the Treatment of Eosinophilic Asthma

Recent advances predict a bright future for nebulizers

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