Fasenra significantly reduced exacerbation rate for severe eosinophilic asthma patients in Phase IIIb ANDHI trial
Improvements also demonstrated in quality of life, lung function and nasal polyposis symptoms
05 August 2020
Results from the positive Phase IIIb ANDHI trial showed AstraZeneca’s Fasenra (benralizumab), when given on top of standard of care, demonstrated a statistically significant 49% reduction in the annual rate of asthma exacerbations at week 24 compared to placebo (0.94 vs. 1.86; p≤0.0001) in patients with baseline blood eosinophil counts greater than or equal to 150 cells per microlitre.1
These data were presented today at the American Thoracic Society 2020 Virtual International Conference.1
In key secondary endpoints, Fasenra demonstrated a statistically significant and clinically meaningful improvement in health-related quality of life at week 24 compared to placebo (p≤0.0001), with similar differences seen at all earlier time points, as measured by the St. George's Respiratory Questionnaire (SGRQ).1
Fasenra also demonstrated early improvements in lung function, as measured by forced expiratory volume in one second (FEV1) of up to 160ml at week 24, compared to placebo (p<0.0001), as well as improvements in asthma control (p≤0.001), as measured by the Asthma Control Questionnaire 6 (ACQ-6).1
In a subgroup of patients with chronic rhinosinusitis with nasal polyposis (NP) at baseline, Fasenra demonstrated a clinically relevant improvement in symptoms at week 24 compared to placebo (p=0.0204), with similar differences seen at all earlier time points, as measured by the Sino-Nasal Outcome Test (SNOT-22).1,2
Tim Harrison, Professor of Asthma and Respiratory Medicine, University of Nottingham, UK, and investigator in the ANDHI trial, said: “Severe asthma is a debilitating disease and many patients remain uncontrolled on standard of care treatment. These data should provide further confidence to physicians that early and sustained improvements in quality of life, lung function and asthma control can be achieved with Fasenra in patients with severe eosinophilic asthma. In addition, the nasal polyps subgroup data in the trial warrants further investigation and exploration of Fasenra’s potential in this disease.”
Mark White, Global Franchise Head, Fasenra, said: “These new data reinforce Fasenra’s ability to reduce asthma exacerbations as well as positively impact other measures that are important to patients. The nasal polyps data included is promising and we continue to investigate Fasenra’s potential to help improve outcomes for nasal polyp patients in our ongoing Phase III OSTRO trial.”
The safety and tolerability of Fasenra were consistent with the known profile of the medicine. The most commonly reported adverse events (AEs) included headache, nasopharyngitis, sinusitis, pyrexia and bronchitis. Fewer serious AEs were reported in the Fasenra group (5.4%) versus placebo (10.9%).1
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 and EU and other key markets. In January 2020, AstraZeneca announced Fasenra is being evaluated in eight eosinophil-driven diseases beyond severe asthma, including NP.
Asthma affects approximately 339 million individuals worldwide.3,4 Approximately 10% of asthma patients have severe asthma, which may be uncontrolled despite high dosages of standard-of-care asthma controller medicines and can require the use of long-term oral corticosteroids (OCS).5,6,7 Severe, uncontrolled asthma is debilitating and potentially fatal, with patients experiencing frequent exacerbations and significant limitations on lung function and health-related quality of life.5,7-9 Severe, uncontrolled asthma has a greater risk of mortality than severe asthma.7 50% or more of people with severe asthma have elevated counts of eosinophils, white blood cells that are a normal part of the immune system and can drive airway inflammation in some patients.6,7,10-12
Severe, uncontrolled asthma can lead to a dependence on OCS, with cumulative steroid exposure leading to serious short- and long-term adverse effects including weight gain, diabetes, osteoporosis, glaucoma, anxiety, depression, cardiovascular disease and immunosuppression.13-15 There is also a significant physical and socio-economic burden of severe, uncontrolled asthma with these patients accounting for 50% of asthma-related costs despite compromising approximately 10% of the asthma population.6,16
Chronic rhinosinusitis with nasal polyposis
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterised by persistent inflammation of the mucosa lining the inside of the nose and paranasal sinuses, accompanied by benign inflammatory masses, known as nasal polyps, arising from the mucosa of the nose and paranasal sinuses.17,18
The estimated prevalence of CRSwNP is 1-4%.19,20 In patients with CRSwNP, elevated levels of eosinophils accumulate in the inflamed tissues and this eosinophilic inflammation is believed to potentially contribute to key pathological mechanisms in CRSwNP.21,22 Around 60-90% of CRSwNP patients have been found to demonstrate eosinophil-dominant infiltration.21,22
Clinical manifestations of CRSwNP include nasal obstruction, reduction in the sense of smell, nasal discharge, sleep disturbance and adverse effects on quality of life.23-25
Surgery to remove polyps may be required in patients in whom symptoms are not controlled by intranasal or oral corticosteroids. However, the rates of relapse and the need for repeated interventions can be high. There are currently only two biologics approved to treat NP. 23,24
ANDHI is a Phase IIIb, randomised, double-blind, placebo controlled, parallel group, 24-week trial to evaluate the safety and efficacy of Fasenra 30mg subcutaneous injection compared to placebo in patients with severe asthma uncontrolled on standard of care treatment.1 The trial was conducted to extend knowledge and understanding of the efficacy and safety of Fasenra for severe, eosinophilic asthma patients, including onset of effect and additional health-related quality of life (HRQOL) measures.1
The primary endpoint is a reduction in the annual rate of asthma exacerbations with Fasenra compared to placebo.1 Secondary endpoints included St. George’s Respiratory Questionnaire (SGRQ) total score, FEV1, and Asthma Control Questionnaire 6 (ACQ-6).1 Sino-Nasal Outcome Test-22 (SNOT-22) was examined for a subset of patients with a comorbid NP at baseline.1
ANDHI involved 656 patients all of whom had baseline eosinophil counts greater than or equal to 150 cells per microlitre and had experienced at least two asthma exacerbations while on maintenance inhaled corticosteroids plus another asthma controller that required treatment with systemic corticosteroids in the previous 12 months.
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).26,27
Fasenra is AstraZeneca’s first respiratory biologic, now approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries, with further regulatory reviews ongoing. In the US, Fasenra is approved for self-administration in the Fasenra Pen.28 In the EU, Fasenra is approved for self-administration in either the single-use, pre-filled syringe or the Fasenra Pen.29
Fasenra is also in development for severe nasal polyposis, other eosinophilic diseases, and chronic obstructive pulmonary disease.30-39 The US Food and Drug Administration granted Orphan Drug Designation for Fasenra for the treatment of eosinophilic granulomatosis with polyangiitis in November 2018,34 hypereosinophilic syndrome in February 201936 and eosinophilic oesophagitis in August 2019.32
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 is one of AstraZeneca’s three therapy areas and is a key growth driver for the Company.
Building on a 50-year heritage, AstraZeneca is an established leader in respiratory care, across inhaled and biologic medicines AstraZeneca aims to transform the treatment of asthma and chronic obstructive pulmonary disease (COPD) by eliminating preventable asthma attacks across all severities and removing COPD as a leading cause of death through earlier biology-led treatment. 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 rheumatology (including systemic lupus erythematosus), dermatology, gastroenterology, and systemic eosinophilic-driven diseases. AstraZeneca’s ambition in immunology is to achieve disease control and ultimately clinical remission in targeted immune-driven diseases.
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal and 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.
- Harrison TW, et al. Exacerbation Reduction and Early and Sustained Improvements in SGRQ, Lung Function, and Symptoms of Nasal Polyposis with Benralizumab for Severe, Eosinophilic Asthma: Phase IIIb ANDHI Trial. ATS Scientific Symposium. Poster Discussion Session. B101. NEW BIOLOGICAL TREATMENTS FOR ASTHMA. Abstract A4274. August 5 2020.
- Hopkins, C. Psychometric validity of the 22-item Sinonasal Outcome Test. Clinical Otolaryngology. 2009; 34, 447–454.
- Chanez P, Humbert M. European respiratory review: Asthma: still a promising future? European Respiratory Review. 2014, 23 (134) 405-407.
- The Global Asthma Network. The Global Asthma Report 2019. [Online]. Available at: http://www.globalasthmanetwork.org/publications/Global_Asthma_Report_2019.pdf.[ Last accessed: July 2020].
- 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.
- Wenzel, Severe Asthma in Adults. Am J Respir Crit Care Med. 2005; 172 VOL 172; 149–160, 2005.
- 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.
- Zhang, JY and Wenzel, SE. Tissue and BAL based biomarkers in asthma. Immunol Allergy Clin North Am. 2007; 27: 623–632 (vi.).
- Fernandes AG, Souza-Machado C, Coelho RC et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014; 40(4): 364-372.
- Schleich F, Demarche S, Louis R. Biomarkers in the Management of Difficult Asthma. Current Topics in Medicinal Chemistry. 2016;16(14):1561-1573.
- Aslan F, Altun E, Paksoy S, Turan G. Could Eosinophilia predict clinical severity in nasal polyps? Multidisciplinary Respiratory Medicine. 2017;12(1).
- Leckie MJ, Brinke AT, Khan J, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsìveness, and the late asthmatic response. The Lancet. 2000;356(9248):2144-2148.
- Sweeney J, et al. Thorax 2016;71:339–346
- 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
- Zeiger RS et al. J Allergy Clin Immunol Pract 2017;5:1050–1060;
- World Allergy Organization (WAO). The management of severe asthma: economic analysis of the cost of treatments for severe asthma. Available from: http://www.worldallergy.org/educational_programs/world_allergy_forum/anaheim2005/blaiss.php. [Last accessed: July 2020].
- Bachert C, Akdis CA. Phenotypes and Emerging Endotypes of Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2016; 4 (4): 621-628.
- Newton JR, Ah-See KW. A review of nasal polyposis. Ther Clin Risk Manag. 2008; 4 (2): 507-512
- Zhang Y, Gevaert E, Lou H, et al. Chronic rhinosinusitis in Asia. J Allergy Clin Immunol. 2017; 140 (5): 1230-1239.
- Beule A. Epidemiology of chronic rhinosinusitis, selected risk factors, comorbidities, and economic burden. GMS Curr Top Otorhinolaryngol Head Neck Surg. 2015; 14: Doc11.
- Fujieda S Imoto Y, Kato Y, et al. Eosinophilic chronic rhinosinusitis. Allergology Int. 2019; 68 (4): 403-412.
- Benjamin MR, Stevens WW, Li N, et al. Clinical Characteristics of Patients with Chronic Rhinosinusitis without Nasal Polyps in an Academic Setting. J Allergy Clin Immunol Pract. 2019; 7 (3): 1010-1016.
- Hopkins C. Chronic Rhinosinusitis with Nasal Polyps. N Engl J Med. 2019; 381 (1): 55-63
- Stevens WW, Schleimer RP, Kern RC. Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract. 2016; 4 (4): 565-572.
- Abdalla S, Alreefy H, Hopkins C. Prevalence of sinonasal outcome test (SNOT-22) symptoms in patients undergoing surgery for chronic rhinosinusitis in the England and Wales National prospective audit. Clin Otolaryngol. 2012; 37 (4): 276-282.
- Kolbeck R, Kozhich A, Koike M, 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 (6): 1344-1353.e2.
- Pham TH, Damera G, Newbold P, Ranade K. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016; 111: 21-29.
- 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: July 2020].
- 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: July 2020].
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- 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: July 2020].
- AZ data on file (MESSINA trial).
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