ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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Velsecorat (AZD7594), a Selective Glucocorticoid Receptor Modulator (SGRM) Demonstrates Favorable Pre-Clinical Efficacy vs Safety Profile Compared to Current Clinical Inhaled Steroid, Fluticasone Furoate
Session Title
TP9 - TP009 MECHANISTIC AND TRANSLATIONAL ASTHMA STUDIES
Abstract
A1418 - Velsecorat (AZD7594), a Selective Glucocorticoid Receptor Modulator (SGRM) Demonstrates Favorable Pre-Clinical Efficacy vs Safety Profile Compared to Current Clinical Inhaled Steroid, Fluticasone Furoate
Author Block: J. W. Pinkerton1, B. Dekkak1, D. Zervas1, T. Markou1, A. Borde2, I. Dainty2, L. Jinton2, D. Sutton2, J. Cartwright2, D. Muthas2, J. Atkinson2, P. Åberg2, A. Aurell-Holmberg2, M. G. Belvisi2, M. Birrell2; 1Imperial College London, London, United Kingdom, 2AstraZeneca, Mölndal, Sweden.
Rationale: Current ‘gold-standard’ therapies for asthma include inhaled corticosteroids (ICS), such as fluticasone furoate (FF). They suppress the underlying inflammation driving the disease, leading to improved patient status. However, long-term steroid use is associated with several unwanted systemic side-effects such as muscle-loss, osteoporosis, reduced bone growth and increased risk of infection. Selective glucocorticoid receptor modulators (SGRMs) are a class of drug which are typically non-steroidal in structure and are designed to bind and activate the glucocorticoid receptor in the lung to maintain the beneficial effects of ICS but have reduced or fewer systemic side-effects. Methods: To test this hypothesis, we assessed the efficacy and side-effect profile of velsecorat (AZD7594) in preclinical rodent model systems and compared this profile with the clinical steroid, FF. Results: Velsecorat caused a dose-related suppression of airway inflammation (Fig. 1) and associated Late Asthmatic Response (LAR). The potency of velsecorat on BAL eosinophilia was similar to the clinical comparator FF, suggesting that they have similar efficacy profiles. When we measured systemic side effects such as loss of body weight, metabolic biomarkers and inhibition of femorotibial bone growth plate thickness (Fig. 1), increased doses of velsecorat were required in comparison with FF. These data suggest that in this in vivo system velsecorat has a beneficial therapeutic index compared to the clinically prescribed ICS, FF. Conclusion: These exciting data suggest that velsecorat, when dosed appropriately, possesses the beneficial effects of ICS with fewer of the side-effects that plague this class of compound. velsecorat, currently in phase 2 clinical trials, represents a new therapeutic opportunity for patients with asthma.
Author Block: J. W. Pinkerton1, B. Dekkak1, D. Zervas1, T. Markou1, A. Borde2, I. Dainty2, L. Jinton2, D. Sutton2, J. Cartwright2, D. Muthas2, J. Atkinson2, P. Åberg2, A. Aurell-Holmberg2, M. G. Belvisi2, M. Birrell2; 1Imperial College London, London, United Kingdom, 2AstraZeneca, Mölndal, Sweden.
Rationale: Current ‘gold-standard’ therapies for asthma include inhaled corticosteroids (ICS), such as fluticasone furoate (FF). They suppress the underlying inflammation driving the disease, leading to improved patient status. However, long-term steroid use is associated with several unwanted systemic side-effects such as muscle-loss, osteoporosis, reduced bone growth and increased risk of infection. Selective glucocorticoid receptor modulators (SGRMs) are a class of drug which are typically non-steroidal in structure and are designed to bind and activate the glucocorticoid receptor in the lung to maintain the beneficial effects of ICS but have reduced or fewer systemic side-effects. Methods: To test this hypothesis, we assessed the efficacy and side-effect profile of velsecorat (AZD7594) in preclinical rodent model systems and compared this profile with the clinical steroid, FF. Results: Velsecorat caused a dose-related suppression of airway inflammation (Fig. 1) and associated Late Asthmatic Response (LAR). The potency of velsecorat on BAL eosinophilia was similar to the clinical comparator FF, suggesting that they have similar efficacy profiles. When we measured systemic side effects such as loss of body weight, metabolic biomarkers and inhibition of femorotibial bone growth plate thickness (Fig. 1), increased doses of velsecorat were required in comparison with FF. These data suggest that in this in vivo system velsecorat has a beneficial therapeutic index compared to the clinically prescribed ICS, FF. Conclusion: These exciting data suggest that velsecorat, when dosed appropriately, possesses the beneficial effects of ICS with fewer of the side-effects that plague this class of compound. velsecorat, currently in phase 2 clinical trials, represents a new therapeutic opportunity for patients with asthma.
