New analyses in real-world setting support the effectiveness of Fasenra in severe eosinophilic asthma

Fasenra reduced exacerbations by 84% in the overall population and results were consistent across all subgroups

The first multi-country analysis from the XALOC programme

New findings from the XALOC programme support the real-world effectiveness of Fasenra (benralizumab) in the management of patients with severe eosinophilic asthma (SEA), showing reductions in annualised asthma exacerbation rate (AAER), improvements in asthma control and the ability to achieve clinical remission.^1,2

Results from the first integrated multi-country retrospective analysis from XALOC-1 showed that Fasenra treatment was associated with an AAER reduction of 84%, at Week 48 (AAER 0.54 [95% confidence interval {CI}: 0.47, 0.63]), compared to baseline (AAER 3.37 [95% CI: 3.17, 3.58]), in an overall patient population with SEA and more than 12 months of Fasenra treatment. Additionally, a reduction in AAER of 79–91% was observed across patient subgroups, regardless of atopic status, CRSwNP comorbidity, maintenance oral corticosteroid (OCS) use, fractional exhaled nitric oxide (FeNO) and blood eosinophil cut-offs. The XALOC-1 analysis included 797 patients with SEA.¹

In a separate interim analysis from the prospective ImPROve Asthma study, part of XALOC-2, Fasenra showed clinically meaningful improvements across patient-reported outcome measures (ACT: Asthma Control Test; ACQ-6: Asthma Control Questionnaire; SGRQ: St George’s Respiratory Questionnaire) in the total SEA cohort and those also with CRSwNP. Over a third (35%, n=32/92) of patients with SEA achieved clinical remission at 6 months following treatment with Fasenra in a real-world setting. In patients with SEA and comorbid CRSwNP the proportion increased, with 44% (n=15/34) achieving clinical remission. Clinical remission was assessed by a proposed composite endpoint definition which included no exacerbations, no maintenance OCS use, asthma symptom control (ACT ≥20) and no decrease of forced expiratory volume in the first second (FEV1) greater than or equal to 200 mL vs baseline. The ImPROve analysis included 205 patients with SEA in Germany.²

Professor David Jackson, Severe Asthma Centre, Guy’s and St Thomas’ NHS Trust and Principal Investigator of XALOC-1, said: “This exciting real-world evidence showed that treatment with Fasenra was associated with important reductions in exacerbations for patients across all the main subgroups of severe eosinophilic asthma. As we strive to improve outcomes for our patients, furthering our understanding of the effectiveness of severe asthma treatments in the real world is critical.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “The XALOC results reflect the real-world effectiveness of Fasenra to reduce asthma exacerbations and positively impact other outcome measures that are important to severe asthma patients. The interim results from the ImPROve analysis are promising and add to the emerging body of evidence supporting the concept of clinical remission as a treatment goal.”

These findings were presented today at the European Respiratory Society (ERS) International Congress 2022 (#PA4187. Tuesday 6 September, 13:00-14:00 CEST, session 468), (#PA4189. Tuesday 6 September, 13:00-14:00 CEST, session 468).

The most commonly reported adverse reactions during treatment with Fasenra are headache (8%) and pharyngitis (3%) in clinical trials (n=2514) of 48 to 56 weeks duration.³

Fasenra is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries, and is approved for self-administration in the US, EU and other countries.

Notes

Severe asthma 
Severe asthma is an often-debilitating, potentially fatal condition affecting approximately 34 million people worldwide.^4,5,6 Patients may be uncontrolled despite high dosages of standard of care asthma controller medicines, experiencing frequent exacerbations and significant limitations on lung function and health-related quality of life as a result.^5,6,7

XALOC
The XALOC real-world evidence programme was established to assess the real-world effectiveness of Fasenra. XALOC-1 is an international, retrospective study of adults with SEA and greater than or equal to 12 months of Fasenra use. It will include more than 750 patients from across five individual studies within Canada, Italy, Spain and UK. ¹ XALOC-2 is an international prospective real-world study of Fasenra in patients with SAE. It will include more than 400 patients from across four individual studies within Canada, Belgium, Switzerland and the ImPROve Asthma study in Germany. ²  

Fasenra 
Fasenra (benralizumab) is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of eosinophils via apoptosis (programmed cell death).^8,9 

Fasenra is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries, and is approved for self-administration in the US, EU and other countries. Fasenra has been studied in almost 4,000 patients in global clinical trials.^9-14

Fasenra was developed by AstraZeneca and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Kirin Co., Ltd., Japan. 

AstraZeneca in Respiratory & Immunology 
Respiratory & Immunology, part of BioPharmaceuticals, is one of AstraZeneca’s main disease areas and a key growth driver for the Company.

AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. We are committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a portfolio of inhaled and biologic medicines. Our pipeline for the future aims to address the vast unmet medical needs of patients by targeting the underlying biology of disease, advancing new drug modalities and combinations, driving earlier diagnosis and applying a precision medicine approach to our early research.

Our ambition is to transform care in respiratory & immune-mediated diseases by moving beyond symptom control to achieve disease modification, remission and, one day, cures for the millions of patients worldwide.

AstraZeneca 
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca. 

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References

1. Jackson D, et al. Asthma exacerbation rate reduction with benralizumab in an integrated analysis of the real-world XALOC-1 study. ERS Thematic poster presentation: PA4187. Presentation at the European Respiratory Society (ERS) International Congress 2022, 6 September 2022; 13:00-14:00 CEST.

2. Korn S, et al. Early response and remission with benralizumab in patients with severe asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP) in the prospective real-world ImPROve Asthma study. ERS Thematic poster presentation: PA4189. Presentation at the European Respiratory Society (ERS) International Congress 2022, 6 September 2022; 13:00-14:00 CEST.

3. European Medicines Agency. Fasenra, Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/fasenra-epar-product-information_en.pdf. [Last accessed September 2022].

4. The Global Asthma Network. The Global Asthma Report 2018. [Online]. Available at: http://globalasthmareport.org/resources/Global_Asthma_Report_2018.pdf. [Last accessed: September 2022].

5. Chung KF, et al. International ERS/ATS guidelines on definition, evaluation, and treatment of severe asthma. Eur Respir J 2014; 43: 343–73.

6. Wenzel, Severe Asthma in Adults. Am J Respir Crit Care Med. 2005;172:149–160.

7. Peters SP, et al. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med 2006:100:1139-51.

8. Kolbeck R, et al. MEDI-563, a humanized anti–IL-5 receptor a mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010;125:1344-1353.e2.

9. Pham TH, et al. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016;111:21-29.

10. Bleecker ER, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β 2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388:2115-2127.

11. FitzGerald JM, et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388:2128-2141.

12. Nair P, et al. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017;376:2448-2458.

13. Menzies-Gow A, et al. Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, single-arm study. Lancet Respir Med. 2022;10:47-58.

14. Harrison TW, et al. Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial. Lancet Respir Med. 2021;9:260-274.