secondary endpoints in pivotal trials for severe asthma
LONDON, UK I September 5, 2016 I Results from pivotal Phase III trials presented at the European Respiratory Society (ERS) International Congress demonstrated that adding benralizumab to standard-of-care medicine significantly reduced exacerbations and improved lung function and asthma symptoms in severe asthma patients with an eosinophilic phenotype, as indicated by the presence of eosinophils in their blood.
The SIROCCO and CALIMA trials evaluated the effect of two dosing regimens of benralizumab 30mg administered in 4-week and 8-week regimens as add-on therapy to standard-of-care medicine across primary and key secondary endpoints. Results showed:
- Reductions in the annual rate of asthma exacerbations (up to 51%)
- Improvement in lung function (change in FEV1 of up to 159 mL), which was seen at 4 weeks after the first benralizumab dose and sustained throughout the treatment period
- Improvement in asthma symptoms, such as wheeze, cough, chest tightness and shortness of breath
The outcomes were demonstrated for the 8-week dosing regimen, with no additional benefit observed with 4-week dosing, which may support less-frequent dosing. In addition, post-hoc analysis showed greater improvements in exacerbation rate reduction, FEV1 and total asthma symptom scores in patients with a history of more frequent asthma exacerbations (≥ 3 in the previous year). Detailed results were published today in The Lancet for the Phase III SIROCCO and CALIMA trials.
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: “Severe asthma affects the lives of millions of patients around the world and can be life threatening. The SIROCCO and CALIMA Phase III trials have shown that benralizumab can offer a meaningful treatment option for patients as evidenced by reductions in exacerbations, improvement in lung function and symptoms, with the promise of fewer doses a year. Benralizumab has a unique way of working in patients with severe asthma with an eosinophilic phenotype and reflects AstraZeneca’s progress in bringing the next generation of respiratory medicines to patients.”
The adverse event frequency was similar between benralizumab-treated patients versus placebo-treated patients for both SIROCCO and CALIMA (72% and 74% for all benralizumab treated patients vs. 76% and 78% for placebo-treated patients observed in SIROCCO and CALIMA, respectively). The most common (≥5%) adverse events in benralizumab-treated patients observed in SIROCCO were asthma, nasopharyngitis, upper respiratory infection, headache, bronchitis, sinusitis, influenza and pharyngitis; and in CALIMA were nasopharyngitis, asthma, bronchitis, upper respiratory tract infection, headache and sinusitis.
Severe uncontrolled asthma is a debilitating and potentially fatal form of the disease, where patients experience frequent exacerbations every year and have significant limitations on lung function and quality of life. Uncontrolled asthma can lead to a dependence on oral corticosteroids (OCS), with systemic steroid exposure leading to serious and irreversible adverse effects.
Benralizumab is an anti-eosinophil monoclonal antibody that induces direct, rapid and near-complete depletion of eosinophils, with an onset of action within 24 hours as confirmed in early phase I/II trials. Eosinophils are the biological effector cells that drive inflammation and airway hyper-responsiveness in approximately 50% of asthma patients, leading to frequent exacerbations, impaired lung function and asthma symptoms.
The data from the SIROCCO and CALIMA trials will be included in regulatory submissions for benralizumab that are planned for the US and EU later in 2016.
NOTES TO EDITORS
About Severe Asthma
Asthma currently affects the health and day-to-day lifestyles of 315 million individuals worldwide, and by 2020 will likely increase in numbers to as many as 400 million people. Up to 10% of asthma cases are severe, of which approximately 40% remain uncontrolled on current standard of care medicine. Severe, uncontrolled asthma has an eight times higher risk of mortality than severe asthma. Uncontrolled asthma can lead to a dependence on OCS. Systemic steroid exposure can lead to serious and irreversible adverse effects, including osteoporosis, anxiety, depression, weight gain, glaucoma and diabetes. There is also a significant physical and socio-economic burden of severe asthma with these patients accounting for 50% of asthma-related costs.
About the WINDWARD Programme
The WINDWARD programme in asthma is made up of six Phase III trials, including SIROCCO, CALIMA, ZONDA, BISE, BORA and GREGALE. WINDWARD, the largest Phase III development programme for a biologic medicine in respiratory disease, evaluated a total of 3,068 patients in 798 sites across 26 countries.
The two pivotal trials, SIROCCO and CALIMA, are randomised, double-blind, parallel-group, placebo-controlled trials designed to evaluate the efficacy and safety of a regular, subcutaneous administration of benralizumab (fixed 30mg dose) for up to 56 weeks in exacerbation-prone adult and adolescent patients 12 years of age and older.
A total of 2,511 patients (1,205 in SIROCCO and 1,306 in CALIMA) currently receiving standard of care medicine (including high-dosage inhaled corticosteroids and long-acting beta 2 agonists [ICS/LABA]) were randomised globally and received either benralizumab 30mg every 4 weeks; benralizumab 30mg every 4 weeks for the first three doses followed by 30mg every 8 weeks; or placebo. All benralizumab doses were administered via subcutaneous injection using an accessorized pre-filled syringe.
In addition to WINDWARD, the Phase III VOYAGER programme is currently underway, which is evaluating the efficacy and safety of benralizumab in patients with severe chronic obstructive pulmonary disease (COPD).
About Benralizumab
Benralizumab was developed by MedImmune, AstraZeneca’s global biologics research and development arm and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Hakko Kirin Co., Ltd.
About AstraZeneca in Respiratory Disease
Respiratory disease is one of AstraZeneca’s main therapy areas, and we have a growing portfolio of medicines that reached more than 17 million patients in 2015. Our 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. We are building on a 40-year heritage in respiratory disease, and our capability in inhalation technology spans both pressurised metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs), as well as our unique Co-SuspensionTM Delivery Technology. Our research is focused on three key biological pathways: eosinophilic disease, Th2-driven disease and epithelial-driven pathobiology.
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 – Respiratory and Autoimmunity, Cardiovascular and Metabolic Diseases, and Oncology. The company is also active in inflammation, infection and neuroscience through numerous collaborations. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com
SOURCE: AstraZeneca
