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.
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. 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. FASENRA is not approved for the treatment of other eosinophilic conditions or relief of acute bronchospasm or status asthmaticus.
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.
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. 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.
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.
IMPORTANT SAFETY INFORMATION
Known hypersensitivity to benralizumab or excipients.
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA. These reactions generally occur within hours of administration, but in some instances have a delayed onset (ie, days). Discontinue in the event of a hypersensitivity reaction.
Acute Asthma Symptoms or Deteriorating Disease
FASENRA should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.
Reduction of Corticosteroid Dosage
Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.
Parasitic (Helminth) Infection
It is unknown if FASENRA will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with FASENRA. If patients become infected while receiving FASENRA and do not respond to anti-helminth treatment, discontinue FASENRA until infection resolves.
The most common adverse reactions (incidence ≥ 5%) include headache and pharyngitis.
Injection site reactions (eg, pain, erythema, pruritus, papule) occurred at a rate of 2.2% in patients treated with FASENRA compared with 1.9% in patients treated with placebo.
USE IN SPECIFIC POPULATIONS
The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies such as benralizumab are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy.
FASENRA is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype.
- FASENRA is not indicated for treatment of other eosinophilic conditions
- FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus
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NOTES TO EDITORS
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 weeks), CALIMA (56 weeks) and ZONDA (28 weeks), 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. Analyzed patients had blood eosinophil counts of 300 cells/μL or greater (SIROCCO/CALIMA) or of 150 cells/μL or greater (ZONDA) at baseline.
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.
About severe asthma
Asthma affects approximately 26.5 million individuals in the US. Up to 10% of asthma patients have severe asthma, which may be uncontrolled despite high doses of standard-of-care asthma controller medicines and can require the use of chronic oral corticosteroids (OCS). Severe, uncontrolled asthma is debilitating and potentially fatal with patients experiencing frequent exacerbations and significant limitations on lung function and quality of life. Severe, uncontrolled asthma has a higher risk of mortality than severe asthma.
Severe, uncontrolled asthma can lead to a dependence on OCS, with systemic steroid exposure potentially leading to serious short- and long-term adverse effects including weight gain, diabetes, osteoporosis, glaucoma, anxiety, depression, cardiovascular disease and immunosuppression. There is also a significant physical and socioeconomic burden of severe, uncontrolled asthma with these patients accounting for 50% of asthma-related costs despite comprising only 10% of the asthma population.
Clinical features associated with an eosinophilic phenotype that can act as markers for enhanced efficacy with targeted therapy in severe eosinophilic asthma include: greater baseline blood eosinophil counts, a history of more frequent exacerbations, chronic OCS use and a history of nasal polyposis.
FASENRA is a monoclonal antibody that binds directly to the IL-5α receptor on eosinophils, and attracts natural killer cells to induce rapid and near-complete depletion of eosinophils via apoptosis (programmed cell death). Eosinophils are a type of white blood cell that are a normal part of the body's immune system and elevated levels of eosinophils are seen in about half of severe asthma patients. Elevated levels of eosinophils impact airway inflammation and airway hyperresponsiveness, resulting in increased asthma severity and symptoms, decreased lung function and increased risk of exacerbations.
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, and under regulatory review in several other jurisdictions. Where approved, FASENRA is available as a fixed-dose subcutaneous injection via a prefilled syringe administered once every 4 weeks for the first 3 doses, and then once every 8 weeks thereafter.
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 disease is one of AstraZeneca’s main therapy areas, and the Company has a growing portfolio of medicines that reached more than 18 million patients in 2018. AstraZeneca’s aim is to transform asthma and chronic obstructive pulmonary disease (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 pressurized metered-dose inhalers and dry powder inhalers, as well as the AEROSPHERE™ Delivery Technology. The Company has a growing portfolio of respiratory biologics including benralizumab (anti-IL-5rɑ), which is also in development for severe nasal polyposis and other eosinophilic conditions, and has been granted Orphan Drug Designation by the US Food and Drug Administration for eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES). Tezepelumab (anti-TSLP) has also been granted Breakthrough Therapy Designation in patients with severe asthma and is in Phase III trials. AstraZeneca’s research is focused on addressing underlying disease drivers focusing on the lung epithelium, lung immunity and lung regeneration.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization 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 www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
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