Globally, as many as 13.5 million people living with severe asthma rely on frequent or maintenance use of oral corticosteroids (OCS) to treat moderate-to-severe exacerbations and decrease the risk of hospital visits or hospitalisations.1,2,3,4 In fact, respiratory diseases are the most frequently recorded indication for OCS treatment.5 Chronic use of OCS, however, carries potential for serious systemic complications and health risks including diabetes mellitus, osteoporosis, heart disease and immunosuppression.6,7,8 This over-reliance can cause significant and unnecessary clinical and economic burden to patients and healthcare systems, requiring the severe asthma community to address ways to improve the care that patients receive, including adopting OCS-sparing strategies where possible.8,9
AstraZeneca is committed to improving care for severe asthma patients, including developing strategies to curb reliance on chronic OCS where appropriate. Building on findings from the Phase III ZONDA OCS-sparing trial, in 2018, we broke new ground with the start of the PONENTE clinical trial with Fasenra (benralizumab). This trial is designed to provide valuable evidence for clinicians on reducing or eliminating long-term OCS use while maintaining asthma symptom control.10
Recognising the trial’s potential to drive future guideline changes, PONENTE is being highlighted at the American Thoracic Society (ATS) 2019 International Conference, showcasing its unique trial design that directly addresses key obstacles to OCS-sparing strategies. PONENTE aims to be the largest steroid-sparing trial ever undertaken in severe asthma, with a projected 600 dosed subjects across approximately 180 clinical centres in 17 countries.11 During a 4-week induction phase, a variable OCS tapering phase and a 24–32-week maintenance phase, PONENTE will investigate the efficacy and safety of tapering OCS use, including impact on health-related quality of life.10,11
Compared to previous studies on OCS-sparing in severe asthma, PONENTE has a faster steroid-tapering schedule and includes an adrenal insufficiency evaluation, as well as an algorithm to specifically taper OCS dosage.11 PONENTE also includes a longer maintenance phase to assess asthma control for up to six months after completion of OCS tapering.11
Systemic corticosteroids have been a mainstay of treatment for severe asthma and asthma exacerbations for more than 50 years.12 There is now an opportunity to explore new ways to decrease reliance and minimize long term use and the resulting adverse events. PONENTE will provide valuable clinical evidence for physicians on how they could ensure safe and effective OCS tapering or elimination without losing asthma symptom control in these patients. Study completion is anticipated in the second half of 2020.11
Click here to learn more about AstraZeneca’s activities at ATS 2019.
Read ‘The Economist Room to Breathe: Understanding Severe Asthma’ article to learn more about the unmet need in severe asthma.
1. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014; 43: 343–73.
2. Wenzel, Severe Asthma in Adults. Am J Respir Crit Care Med. 2005; 172 VOL 172; 149–160.
3. Peters SP, Ferguson G, Deniz Y, et al. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med. 2006; 100(7):1139-51.
4. Voorham J, Xu X, Price D, Golam S, Davis J, et al. Health care resource utilization and costs associated with incremental systemic corticosteroid exposure in asthma. Allergy. 2018 July 10.
5. T.P. van Staa, H.G.M. Leufkens, L. Abenhaim, B. Begaud, B. Zhang, C. Cooper, Use of oral corticosteroids in the United Kingdom, QJM: An International Journal of Medicine, Volume 93, Issue 2, February 2000, Pages 105–111.
6. Sweeney J, et al. Thorax. 2016;71:339–346.
7. Hyland ME, Whalley B, Jones RC, et al. A qualitative study of the impact of severe asthma and its treatment showing that treatment burden is neglected in existing asthma assessment scales. Quality of Life Research. 2015; 24 (3) 631-619.
8. Sullivan PW, Ghushchyan VH, Globe G, Schatz M. Oral corticosteroid exposure and adverse effects in asthmatic patients. Journal of Allergy and Clinical Immunology. 2018;141(1).
9. World Allergy Organization (WAO). The management of severe asthma: economic analysis of the cost of treatments for severe asthma. Last accessed April 2018. http://www.worldallergy.org/educational_programs/world_allergy_forum/anaheim2005/blaiss.php.
10. Study to Evaluate Efficacy and Safety of Benralizumab in Reducing Oral Corticosteroid Use in Adult Patients With Severe Asthma (PONENTE). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03557307?term=PONENTE&rank=1. Accessed May 2019.
11. Menzies-Gow A, Corren J, Bel E, et al. Oral Corticosteroid Tapering During Benralizumab Treatment of Severe, Uncontrolled Eosinophilic Asthma: PONENTE Phase IIIb Clinical Trial. Presented at the American Thoracic Society (ATS) International conference, 17-22 May 2019, Dallas, Texas.
12. Zazzali JL, Broder MS, Omachi TA, et al. Risk of corticosteroid-related adverse events in asthma patients with high oral corticosteroid use. Allergy Asthma Proc. 2015;36:268 –74.