AstraZeneca, a British-Swedish multinational pharmaceutical and biologics company, announced that benralizumab, a potential new medicine and anti-eosinophil monoclonal antibody, was well tolerated and achieved the primary endpoint in two pivotal phase III registrational trials (SIROCCO and CALIMA), demonstrating significant reductions in the annual asthma exacerbation rate compared to placebo.

Sean Bohen, executive vice president, global medicines development and chief medical officer, said, “Severe asthma affects the health and quality of life of millions of people around the world, and exacerbations can be life threatening for these patients. We are pleased with the top-line results from these pivotal trials as they demonstrate the potential for benralizumab to improve outcomes for patients with severe asthma. Benralizumab is AstraZeneca’s first respiratory biologic and its development underscores our commitment to transform the treatment of asthma and chronic respiratory disease with our next generation of respiratory medicines.”

The trials evaluated the efficacy and safety of two dose regimens of benralizumab as an add-on therapy for severe uncontrolled asthma with eosinophilic inflammation in adults and adolescents 12 years of age and older.

In SIROCCO and CALIMA, the primary analysis population included patients on high-dose inhaled corticosteroids (ICS) plus long-acting ß2-agonist (LABA) with a baseline blood eosinophil count = 300 cells/microliter. Patients were randomised to receive benralizumab 30mg every 4 weeks; 30mg every 4 weeks for the first three doses followed by 30mg every 8 weeks; or placebo. The safety and tolerability findings for benralizumab were generally consistent with those reported in previous trials.

Mark FitzGerald, MD, director of the Centre for Heart and Lung Health at the Vancouver Coastal Health Research Institute and principal investigator in the CALIMA trial, said, “We are learning more about different sub-types of asthma, and these trials investigate a potential new treatment to address the underlying driver for some patients. Within the appropriate patient population, the anti-eosinophil effect of benralizumab has the potential to deliver uniquely-targeted treatment for patients whose asthma is driven by eosinophilic inflammation.”

Eosinophils are the biological effector cells that drive inflammation and airways hyper-responsiveness in approximately 50 per cent of asthma patients, leading to frequent exacerbations, impaired lung function and reduced quality of life. Benralizumab is an anti-eosinophil monoclonal antibody that depletes eosinophils via antibody-dependent cell-mediated cytotoxicity (ADCC), the process by which natural killer cells are activated to target eosinophils. Benralizumab induces direct, rapid, and near complete depletion of eosinophils in the bone marrow, blood and target tissue. Benralizumab was developed by MedImmune, AstraZeneca’s global biologics research and development arm.

Results from the SIROCCO and CALIMA trials will be presented at a future medical meeting. Regulatory submissions in the US and EU are anticipated in the second half of 2016.

Asthma is a common, chronic condition in which inflammation and narrowing of the airways may cause wheezing, breathlessness, chest tightness and coughing. 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 per cent of asthma cases are severe, of which approximately 40 per cent are uncontrolled. Severe, uncontrolled asthma has eight times higher risk of mortality than severe asthma. Uncontrolled asthma can lead to a dependence on oral corticosteroid (OCS). Systemic steroid exposure leads 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 asthma with severe patients accounting for 50 per cent of asthma-related costs.

SIROCCO and CALIMA are both part of the comprehensive WINDWARD programme in asthma (comprised of six phase III trials in 3,068 patients and 798 sites, across 26 countries), the largest phase III development programme for a biologic in respiratory disease.

The two registrational trials, SIROCCO and CALIMA, are randomised, double-blind, parallel group, placebo-controlled trials designed to evaluate the efficacy and safety of a fixed 30 mg dose of benralizumab administered subcutaneously in patients with a history of asthma exacerbations and uncontrolled asthma receiving ICS/LABA with or without OCS and additional asthma controllers.

A total of 2,511 patients (1,205 in SIROCCO and 1,306 in CALIMA) were randomised globally and received benralizumab 30mg every 4 weeks; 30mg every 4 weeks for the first three doses followed by 30mg every 8 weeks; or placebo.

In addition to WINDWARD, the phase III VOYAGER programme is currently underway, evaluating benralizumab in patients with severe chronic obstructive pulmonary disease (COPD).

Benralizumab is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Hakko Kirin Co., Ltd. Under the exclusive license agreement, Kyowa Hakko Kirin/BioWa have exclusive development and commercialisation rights for benralizumab in Japan and certain countries in Asia. AstraZeneca has exclusive rights for benralizumab in all other countries including the US and Europe. BioWa is eligible to milestone payments and royalties from AstraZeneca related to the development and commercialisation of benralizumab in those countries.  

In July 2015 AstraZeneca entered an agreement with Kyowa Hakko Kirin Co. Ltd. (Kyowa Hakko Kirin) for an exclusive option to commercialise benralizumab for asthma and COPD in Japan. Under the terms of the agreement, AstraZeneca paid Kyowa Hakko Kirin a $45 million up-front option fee and will make subsequent payments for regulatory filing, approval and commercial milestones, and sales royalties. Kyowa Hakko Kirin will continue to be responsible for the research and development of benralizumab in Japan. On exercising the option, AstraZeneca will be responsible for all sales and marketing in asthma and COPD in Japan. Kyowa Hakko Kirin will retain the rights to participate in certain commercial activities alongside AstraZeneca.