Data confirm Fasenra’s well-established safety profile consistent with previous Phase III trials
At least 75% of Fasenra-treated patients with elevated blood eosinophil levels had zero exacerbations each year of the open-label period
Results from a new integrated analysis including data from the MELTEMI Phase III open-label extension trial showed Fasenra (benralizumab) was well-tolerated for up to five years, with a long-term safety profile consistent with previous Phase III trials in adult patients with severe asthma.1
Results were presented today at the American Thoracic Society (ATS) 2021 International Conference.
During the period of the BORA and MELTEMI extension trials, adverse events (AEs) and serious adverse events (SAEs) did not increase from rates comparable to placebo observed in the Phase III pivotal trials.1 Rates of serious infection, hypersensitivity, immunogenicity, and malignancy were low across all treatment groups, with no deaths during the on-treatment window.1 The most commonly reported AEs during the open-label period for patients receiving Fasenra every eight weeks were nasopharyngitis, asthma, headache, and bronchitis.1 These data confirm Fasenra’s well-established safety profile.
In secondary endpoints, Fasenra sustained the reduction in asthma exacerbation rates observed during predecessor SIROCCO,2 CALIMA,3 ZONDA4 and BORA5 Phase III trials with annualised asthma exacerbation rates (AAER) remaining consistently low over the five-year treatment period.1
In patients taking high-dosage inhaled corticosteroids (ICS) with blood eosinophil levels of greater than or equal to 300 cells per microlitre who received Fasenra every eight weeks, AAER decreased from 3.1 exacerbation/year pre-treatment to 0.5 in the predecessor studies with a further reduction to 0.2 by year four of the open-label trial. In the same treatment group 59% of patients experienced zero exacerbations during the four years of the open-label period (BORA and MELTEMI) and at least 75% of patients each year experienced zero exacerbations. In the final year of the trial 87% of patients experienced zero exacerbations.1
Arnaud Bourdin, Head of Pulmonology, Professor of Respiratory Medicine at Arnaud de Villeneuve Hospital, Montpellier, France and primary investigator for MELTEMI, said: “Clinicians treating severe eosinophilic asthma want to ensure the therapy they prescribe will continue to help patients control their illness in the long term, with a consistent safety profile. Based on the new MELTEMI data, physicians and their patients should feel confident that Fasenra provides a treatment option that can do exactly that – reduce exacerbations, with a known safety profile.”
Mark White, Global Franchise Head, Fasenra, said: “The new data from MELTEMI are exciting as they confirm Fasenra’s efficacy and safety profile seen in previously reported Phase III trials. These results should offer further confidence to physicians and patients that the positive outcomes they’re experiencing whilst using Fasenra can be maintained for the longer-term.”
Fasenra is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries6 and is approved for self-administration in the US7 and EU.8 The Food and Drug Administration (FDA) granted Orphan Drug Designation for Fasenra for eosinophilic granulomatosis with polyangiitis (EGPA) (November 2018),9 hypereosinophilic syndrome (HES) (February 2019)10 and eosinophilic esophagitis (EoE) (August 2019).11
Asthma is a heterogeneous disease affecting an estimated 339 million people worldwide.12,13 Approximately 10% of asthma patients have severe asthma.13,14 Despite the use of inhaled asthma controller medicine, currently available biologic therapies and oral corticosteroids (OCS), many severe asthma patients remain uncontrolled.13-15 Due to the complexity of severe asthma, many patients have unclear or multiple drivers of inflammation and may not qualify for or respond well to a current biologic medicine.14-17
Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life.13,14,18 Patients with severe asthma are at an increased risk of mortality and have twice the risk asthma-related hospitalisations.19-21 There is also a significant socio-economic burden, with these patients accounting for 50% of asthma-related costs.22
MELTEMI is a multicentre, open-label safety extension, Phase III trial to assess the safety and tolerability of Fasenra administered subcutaneously in severe, uncontrolled asthma patients on ICS and long-acting beta2-agonists therapy with or without chronic OCS and/or other asthma controllers. Participants had completed one of three Phase III placebo-controlled predecessor trials (SIROCCO, CALIMA, ZONDA), then enrolled in the double-blind BORA safety extension trial, further transitioning into the MELTEMI open-label extension trial.
The integrated analysis results include patients who had received Fasenra for up to five years from the beginning of the treatment period in the predecessor studies. A total of 446 patients were included in the analysis. Of these, 384 (86.1%) completed the on treatment period and 16% were on treatment for greater than or equal to five years. Mean on treatment duration was equal to or greater than three years in each group. As typically observed in longer-term trials, due to the duration of time participants were followed, fewer patients continued through to the later stages of the study than completed the predecessor trials.
The primary endpoint in MELTEMI was Fasenra safety and tolerability, which was measured by rates of AEs and SAEs during the on-treatment period.1,23 The secondary endpoints included a subset of primary and secondary endpoints from the Phase III predecessor studies: annual asthma exacerbations, in-patient hospitalisation, and/or an emergency department visit, absolute blood eosinophil counts over the course of the on-treatment period; and immunogenicity.
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 blood and tissue eosinophils in most patients via apoptosis (programmed cell death).24,25
Fasenra is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries,6 and is approved for self-administration in the US,7 EU8 and other countries.
Fasenra is in development for other eosinophilic diseases and chronic obstructive pulmonary disease. The US Food and Drug Administration granted Orphan Drug Designation for Fasenra for EGPA (November 2018),9 HES (February 2019)10 and EoE (August 2019).11
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 three therapy areas and is a key growth driver for the Company.
AstraZeneca is an established leader in respiratory care, and its inhaled and biologic medicines reached more than 53 million patients in 2019. Building on a 50-year heritage, the Company aims to transform the treatment of asthma and COPD by focusing on earlier biology-led treatment, eliminating preventable asthma attacks, and removing COPD as a top-three leading cause of death. The Company’s early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell-repair processes in disease and neuronal dysfunction.
With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immunology-driven disease areas. The Company’s growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential, in areas including rheumatology (including Systemic Lupus Erythematosus), dermatology, gastroenterology, and systemic eosinophilic-driven diseases. AstraZeneca’s ambition in Respiratory & Immunology is to achieve disease modification and durable remission for millions of patients worldwide.
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 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.
1. Bourdin A, et al. Integrated Safety and Efficacy Among Patients with Severe Asthma Receiving Benralizumab for Up to Five Years. Am J Respir Crit Care Med. 2021 (3 May);203 [Online]. Data presented at American Thoracic Society (ATS) 2021 International Conference. Session: D007 Advances in asthma therapies (19 May 2021). Abstract: A1205.
2. Bleecker ER, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388:2115-2127.
3. FitzGerald JM, et al. Benralizumab, an anti-interleukin-5 receptor alpha 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.
4. Nair P, Wenzel S, Rabe KF, et al, on behalf of the ZONDA trial investigators. Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017;376:2448-2458.
5. Busse WW, et al. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. Lancet Respir Med. 2019 Jan;7(1):46-59. doi: 10.1016/S2213-2600(18)30406-5.
6. AstraZeneca plc. Year-to-date and Q3 2020 results. [Online] https://www.astrazeneca.com/content/dam/az/PDF/2020/q3/Year-to-date_and_Q3_2020_results_announcement.pdf. [Last accessed: April 2021].
7. AstraZeneca news release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-approved-in-the-us-for-self-administration-in-a-new-pre-filled-auto-injector-the-fasenra-pen-04102019.html [Last accessed: April 2021].
8. AstraZeneca news release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-receives-positive-eu-chmp-opinion-for-self-administration-and-the-new-fasenra-pen-a-pre-filled-single-use-auto-injector-01072019.html [Last accessed: April 2021].
9. AstraZeneca news release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2018/us-fda-grants-fasenra-orphan-drug-designation-for-eosinophilic-granulomatosis-with-polyangiitis-26112018.html. [Last accessed: April 2021].
10. AstraZeneca news release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2019/us-fda-grants-fasenra-orphan-drug-designation-for-hypereosinophilic-syndrome.html. [Last accessed: April 2021].
11. AstraZeneca news release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-granted-us-orphan-drug-designation-for-eosinophilic-oesophagitis-28082019.html [Last accessed: April 2021].
12. The Global Asthma Network. The Global Asthma Report 2018. [Online]. Available at: http://www.globalasthmareport.org/Global%20Asthma%20Report%202018.pdf.[Last accessed: April 2021].
13. 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.
14. Wenzel S. Severe Asthma in Adults. Am J Respir Crit Care Med. 2005;172;149–60.
15. Peters SP, Ferguson G, Deniz Y, et al. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med. 2006;100:1139-51.
16. Hyland ME, Masoli M, Lanario JW, et al. A Possible Explanation for Non-responders, Responders and Super-responders to Biologics in Severe Asthma. Explor Res Hypothesis Med. 2019;4:35–38.
17. Tran TN, Zeiger RS, Peters SP, et al. Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma. Ann Allergy Asthma Immunol. 2016;116:37–42.
18. Fernandes AG, Souza-Machado C, Coelho RC, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014;40:364-372.
19. Chastek B, Korrer S, Nagar SP, et al. Economic Burden of Illness Among Patients with Severe Asthma in a Managed Care Setting. J Manag Care Spec Pharm. 2016;22:848–861.
20. Hartert TV, Speroff T, Togias A, et al. Risk factors for recurrent asthma hospital visits and death among a population of indigent older adults with asthma. Ann Allergy Asthma Immunol. 2002;89:467–73.
21. Price D, Fletcher M, van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014;24:14009.
22. World Allergy Organization (WAO). The management of severe asthma: economic analysis of the cost of treatments for severe asthma. Available at: https://www.worldallergy.org/educational_programs/world_allergy_forum/anaheim2005/blaiss.php [Last accessed: April 2021].
23. Clinicaltrials.gov. A Safety Extension Study With Benralizumab for Asthmatic Adults on Inhaled Corticosteroid Plus Long-acting β2 Agonist (MELTEMI). Available at: https://clinicaltrials.gov/ct2/show/NCT02808819?term=MELTEMI+benralizumab&draw=2&rank=1. [Last accessed: April 2021].
24. Kolbeck R, Kozhich A, Koike M, et al. MEDI-563, a humanized anti-IL-5 receptor α mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010; 125: 1344-1353.
25. Pham T, Damera G, Newbold P, et al. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016; 111: 21-29.
Veeva ID: Z4-33456
Date of Preparation: May 2021