Fasenra reduces oral corticosteroid use and maintains long-term efficacy and safety profile in severe eosinophilic asthma

20 May 2019

Integrated analysis of a large cohort of continuously treated patients to be presented at American Thoracic Society 2019 International Conference

A new integrated analysis of Phase III data for Fasenra (benralizumab) shows that patients with severe eosinophilic asthma who were continuously treated with the medicine for up to two years reduced their use of oral corticosteroids (OCS) and experienced a sustained improvement in exacerbation rates, lung function, asthma control and health-related quality of life.1

The analysis, presented today at the American Thoracic Society (ATS) 2019 International Conference, provides long-term efficacy and safety data for Fasenra from the one-year Phase III SIROCCO and CALIMA exacerbation trials, the one-year Phase III BORA extension trial and the 28-week Phase III ZONDA OCS-sparing trial.

The integrated analysis includes 1,161 Fasenra patients, of whom 1,030 are in the SIROCCO/CALIMA/BORA full analysis set and 131 are in the ZONDA/BORA analysis set.

In the integrated analysis of ZONDA and BORA, 75% of patients had at least a 50% reduction in their OCS dosages from baseline after 84 weeks of Fasenra treatment every eight weeks, and 39% of patients had at least a 90% reduction.1 OCS dosage was reduced by 67% by the end of the integrated study period, which was similar to reductions seen in the ZONDA trial of 75% from baseline compared with 25% for placebo.1,4

Colin Reisner, Senior Vice President and Head of Late RIA, R&D BioPharmaceuticals, said: “These new data strengthen Fasenra’s clinical profile and are an important confirmation of its long-term efficacy and safety profile in severe eosinophilic asthma, which is a debilitating, chronic disease.”

J. Mark FitzGerald, MD, Director of the Centre for Heart and Lung Health at the Vancouver Coastal Health Research Institute, and lead investigator, said: “Long-term efficacy and safety data as shown in this Fasenra integrated analysis are important to physicians treating severe asthma. The results can also give confidence to physicians that their ability to reduce patients’ oral corticosteroid use can be maintained long-term, a key treatment goal given the potential for significant adverse effects.”

The integrated analysis demonstrated that the improvements in exacerbation rate, lung function, asthma control and health-related quality of life observed in the SIROCCO/CALIMA trials during the initial one-year treatment period were maintained in continuously-treated patients over the two-year integrated treatment period.1

The safety profile in the integrated analysis was similar to that observed in the SIROCCO, CALIMA, ZONDA and BORA trials, with no increase in the frequencies of overall or serious adverse events.1 The three most common adverse events reported for those SIROCCO or CALIMA patients who received Fasenra and entered BORA were viral upper respiratory infection, upper respiratory tract infection and bronchitis.5

Fasenra is AstraZeneca's first respiratory biologic and is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and several other countries.


About the integrated efficacy and safety analysis
The analysis was conducted to integrate Fasenra efficacy and safety data from the adult completion phase of the BORA long-term extension trial with data from SIROCCO or CALIMA and ZONDA trials.

These analyses include results for 1,161 patients from the three placebo-controlled trials, SIROCCO (48 week), CALIMA (56 week) and ZONDA (28 week) who received Fasenra 30 mg either every 4 weeks (Q4W) or every 8 weeks (Q8W; first three doses Q4W) throughout the respective Phase III trial and one year of BORA. Patients who received placebo in the predecessor trials were excluded from analysis. Analysed patients had blood eosinophil counts of 300 cells per µL or greater (SIROCCO/CALIMA) or of 150 cells per µL or greater (ZONDA) at baseline.1

Results from the one-year BORA extension trial of patients who had completed SIROCCO or CALIMA (patients who received Fasenra or placebo) were published in the Lancet Respiratory Medicine in November 2018.5

About severe asthma
Asthma affects approximately 339 million individuals worldwide.6,7 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).8,9,10 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.8,10,11,12 Severe, uncontrolled asthma has a greater risk of mortality than severe asthma.10 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.9,10,13,14,15

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.16,17,18,19 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.9,20

About Fasenra
Fasenra (benralizumab) is a monoclonal antibody that binds directly to IL-5 receptor α on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of eosinophils via apoptosis (programmed cell death).21,22

Fasenra is AstraZeneca’s first respiratory biologic, now approved as an add-on maintenance treatment in severe eosinophilic asthma in the US, EU, Japan and several other countries, with further regulatory reviews ongoing. Where approved, Fasenra is available as a fixed-dose subcutaneous injection via a prefilled syringe administered once every four weeks for the first three doses, and then once every eight weeks thereafter. Fasenra is also being studied in severe nasal polyposis and other eosinophilic diseases. The US Food and Drug Administration (FDA) granted Orphan Drug Designation for Fasenra for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) in November 2018 and hypereosinophilic syndrome (HES) in February 2019.

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

About AstraZeneca in respiratory diseases
Respiratory is one of AstraZeneca’s main therapy areas, and our medicines reached more than 18 million patients as maintenance therapy in 2018. AstraZeneca’s aim is to transform asthma and COPD treatment through inhaled combinations at the core of care, biologics for the unmet needs of specific patient populations, and scientific advancements in disease modification.

The Company is building on a 40-year heritage in respiratory disease and AstraZeneca’s capability in inhalation technology spans pressurised metered-dose inhalers and dry powder inhalers, as well as the Aerosphere delivery technology. The company also has a growing portfolio of respiratory biologics including Fasenra (anti-eosinophil, anti‒IL-5Rɑ), now approved for severe eosinophilic asthma and in development for severe nasal polyposis and other potential indications, and tezepelumab (anti-TSLP), which has been granted Breakthrough Therapy Designation by the US FDA in patients with severe asthma and is in Phase III trials. AstraZeneca’s research aims at addressing underlying disease drivers by focusing on the lung epithelium, lung immunity, lung regeneration and neuronal functions.

About AstraZeneca
AstraZeneca 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 & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit astrazeneca.com and follow us on Twitter @AstraZeneca.



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