Results from the MIRACLE Phase III trial show treatment with Fasenra resulted in a statistically significant reduction of 74% in annual exacerbation rate in patients in Asia with severe eosinophilic asthma

Fasenra is under regulatory review for the treatment of severe eosinophilic asthma in China
 

AstraZeneca announced that results from the MIRACLE Phase III trial have been published in Respiratory Medicine demonstrating Fasenra (benralizumab) resulted in a statistically significant and clinically meaningful 74% reduction (rate ratio 0.26 [95% confidence interval (CI) 0.19, 0.36], p<0.0001) in the annualized asthma exacerbation rate (AAER) over 48 weeks compared to placebo (benralizumab n=236, placebo n=237) when added to standard of care in patients in several Asian countries, including China, who have severe eosinophilic asthma (SEA) that is uncontrolled despite treatment.¹

MIRACLE was a randomised, double-blind, placebo-controlled trial in patients with a history of asthma exacerbations and uncontrolled asthma receiving medium- to high-dose inhaled corticosteroid plus long-acting β2-agonist (ICS-LABA) with or without oral corticosteroids and additional asthma controllers. Patients were randomised 1:1 to receive benralizumab 30 mg subcutaneously or placebo over 48 weeks of treatment.^1,2

Uncontrolled severe eosinophilic asthma has considerable disease burden, including low symptom control, poor quality of life, and morbidity.^3,4 In China, the prevalence of severe asthma with eosinophilic phenotype is rising yet treatment options are limited.⁵ Data show that in China, approximately 8-10% of the asthmatic population (estimated at 46 million people) have severe asthma,^6,7,8 and up to 76.8% of those patients have severe eosinophilic asthma.⁹ However, asthma in China remains largely undiagnosed and undertreated.⁶

Dr. Nanshan Zhong, International Coordinating Investigator, MIRACLE trial; Academician of the Chinese Academy of Engineering; The Medal of the Republic Laureate: “The results of the MIRACLE trial confirm that for Chinese patients with severe eosinophilic asthma, the anti-IL-5 receptor monoclonal antibody benralizumab can quickly and sustainably control asthma symptoms and significantly reduce the annual acute exacerbation rate. We are also excited that the study has shown significant treatment efficacy with intervention of benralizumab in asthma patients poorly controlled on medium-dose ICS/LABA.”

Dr. Kefang Lai, National China Principal Investigator, MIRACLE trial; Chair of China Cough Coalition; Director of Clinical Research Department of State Key Lab of Respiratory Disease; Deputy Director of Asthma Consortium, Chinese Thorax Society; Deputy Director of Asthma & Allergy Working Group, Respiratory Branch of the Chinese Medical Doctor Association: “Severe eosinophilic asthma is a debilitating condition impacting quality of life.  In China, many patients are still uncontrolled despite using medium to high dose of inhaled therapies, often experiencing frequent exacerbations, symptom worsening and lung function reduction. The China MIRACLE clinical trial data results are exciting, proving IL-5 receptor monoclonal antibody benralizumab’s clinical treatment effect for patients who have not-well-controlled severe eosinophilic asthma.”

Dr. Jing HE, Senior Vice President, Head of Research and Development, AstraZeneca China: “The positive results from MIRACLE are great news for treating physicians and severe eosinophilic asthma patients in China and other Asian markets, where an unmet medical need remains. These data add to benralizumab’s growing body of evidence in severe eosinophilic asthma and support our application as a treatment for this chronic, debilitating disease to the China National Medical Products Administration. Through our ongoing development programme we intend to bring multiple products to help patients with mild, moderate and severe asthma, confirming our role as a respiratory medicine leader globally, including in China.”

The MIRACLE Phase III trial investigated the efficacy and safety of benralizumab compared to placebo in 695 patients (aged 12 to 75 years) in Asia, primarily China, with a history of uncontrolled severe eosinophilic asthma.^1,2 Patients were randomised to receive 30 mg of benralizumab or placebo every four weeks for the first three doses and then every eight weeks thereafter over a 48-week treatment period.¹

The MIRACLE Phase III trial also achieved statistical significance in the key secondary endpoints, pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV₁) and total asthma symptom score (TASS).¹ Patients in the benralizumab arm demonstrated early (Week 4) and continued (Week 48) improvements in pre-BD FEV₁ (LS mean difference at Week 48 was 0.25 L [95% CI 0.17, 0.34], p<0.0001), and improvements in TASS were observed from Week 20 to Week 48 (LS mean difference at Week 48 was −0.25 [95% CI −0.45, −0.05], p=0.0126), as compared to the placebo.¹ These data demonstrate that benralizumab, which has a unique mechanism of action and convenient dosing scheme,^10,11,12 contributes to improvement in lung function and asthma symptoms.¹

In addition, patients on benralizumab showed a significant and positive improvement in important health-related quality of life, as demonstrated by substantial improvement in their St. George’s Respiratory Questionnaire (SGRQ) total score, from baseline at the first assessment at Week 8 (LS mean difference, −7.36 [95% CI −10.59, −4.13]; nominal p<0.0001) and sustained through Week 48 (−9.19 [95% CI −12.79, −5.60]; nominal p<0.0001).¹

Improvement in pre-BD FEV1, SGRQ and peak expiratory flow (PEF) were observed at first assessment post treatment (i.e., Week 4, 8 and 2, respectively) and sustained through end of treatment (Week 48).¹

The safety and tolerability profile for benralizumab in the China subpopulation was consistent with the overall study population.¹

Benralizumab 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.¹² Benralizumab is currently being evaluated by the Chinese National Medical Products Association for approval for patients with severe eosinophilic asthma. AstraZeneca continues to explore benralizumab's potential as a treatment across many diseases beyond severe asthma where eosinophils are expected to play a role.^13,14,15

Notes

MIRACLE
MIRACLE was a randomised, double-blind, parallel group, placebo-controlled Phase III trial in China, South Korea, and Philippines evaluating the efficacy and safety of Fasenra in 695 patients aged 12 to 75 years of age with a history of uncontrolled asthma who received medium to high-dose inhaled corticosteroid plus long-acting β₂-agonist (ICS-LABA) with or without oral corticosteroids and additional asthma controllers. The primary endpoint was a reduction in the AAER over 48 weeks in patients with severe eosinophilic asthma on 30mg Fasenra SC Q8W compared to placebo, and all patients were randomised to either placebo or Fasenra (1:1 ratio). Patients were stratified by country/region, age group (adult or adolescent), and peripheral blood eosinophil count at time of visit 1 (<300 or ≥300 cells/μL).¹

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 blood and tissue eosinophils in most patients via apoptosis (programmed cell death).¹⁶

Fasenra (benralizumab) is currently approved in more than 80 countries, including the US, EU, Japan, and is approved for self-administration in the US, EU and other countries.^17-20 Fasenra has been prescribed for the treatment of over 120,000 patients globally and has over 15 years of clinical studies supporting safety and efficacy, including the recently published SHAMAL study, the first prospective study demonstrating that SEA patients well controlled with a biologic could reduce background ICS dose while maintaining asthma symptom control.^21,22

Fasenra is in development for other diseases including eosinophilic granulomatosis with polyangiitis (EGPA), chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyps and hypereosinophilic syndrome.^13,14,15,22 Fasenra was developed by AstraZeneca and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Kirin Co., Ltd., Japan.

Severe asthma
Asthma is a major chronic respiratory disease that affects an estimated 300 million people worldwide.¹ Up to 10% of people with asthma have severe asthma that is uncontrolled.¹ Eosinophilic inflammation drives the eosinophilic phenotype of asthma, which is seen in more than 80% of patients with severe asthma.⁹ 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.^23-28

Respiratory and Immunology
Respiratory & Immunology is a key disease area and growth driver for AstraZeneca and part of the Company’s BioPharmaceuticals business.

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 inhaled and biologic medicines today as well as new modalities for the future to address previously unreachable biologic targets. Our ambition is to transform care in respiratory & immune-mediated diseases by movng beyond symptom control to achieve disease modification, remission and, one day, cures for millions of people worldwide. By delivering life-changing medicines and catalysing transformations in care we aim to eliminate COPD as a leading cause of death, eliminate asthma attacks, achieve clinical remission in asthma and transform other respiratory diseases with limited or no treatment options. In immune-mediated disease we aim to deliver clinical remission for the majority of patients and bring much needed treatment options to disease areas with a huge unmet need.

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 social media @AstraZeneca

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References

Veeva ID: Z4-62994
Date of preparation: April 2024