AstraZeneca and its global biologics research and development arm, MedImmune, announced that the Japanese Ministry of Health, Labour and Welfare has approved Fasenra (benralizumab) as an add-on treatment for bronchial asthma in patients who continue to experience asthma exacerbations despite treatment with high-dose inhaled corticosteroid and other asthma controllers.
The approval is based on the results from the WINDWARD programme, including the pivotal phase III exacerbation trials, SIROCCO and CALIMA, and the phase III oral corticosteroid (OCS)-sparing trial, ZONDA. Fasenra will be available as a fixed-dose subcutaneous injection in a prefilled syringe administered once every four weeks for the first three doses, and then once every eight weeks thereafter.
Sean Bohen, executive vice president, global medicines development and chief medical officer at AstraZeneca, said: “The approval of Fasenra, our first respiratory biologic medicine, in Japan closely follows the recent US and EU decisions and brings us another step closer to achieving our ambition of transforming care for severe asthma patients around the world.”
Fasenra binds directly to the IL-5a receptor on eosinophils, a type of white blood cell that are a normal part of the body's immune system, and attracts natural killer cells to induce direct, rapid and near-complete depletion of eosinophils via apoptosis (programmed cell death). Elevated levels of eosinophils, seen in about half of severe asthma patients, impact airway inflammation and airway hyper-responsiveness, resulting in increased asthma severity and symptoms, decreased lung function and increased risk of exacerbations.
The Japanese approval follows US FDA approval in November 2017 and European Commission marketing authorisation in January 2018. Interactions with regulatory authorities in the rest of the world are on-going.
Fasenra is a monoclonal antibody that recruits natural killer cells to induce direct, rapid and near-complete depletion of eosinophils. Depletion of circulating eosinophils is rapid, with an onset of action within 24 hours as confirmed in early Phase I/II trials. Eosinophils are the biological effector cells in approximately 50% of asthma patients, leading to frequent exacerbations, impaired lung function and asthma symptoms.
Fasenra is now approved in the US, EU and Japan, and under regulatory review in several other jurisdictions.
Fasenra is the foundation of AstraZeneca’s respiratory biologics portfolio of potential new medicines targeting underlying causes of respiratory disease. Fasenra is also being evaluated in chronic obstructive pulmonary disease (COPD) with data readout expected in the second half of 2018.
Fasenra was developed by AstraZeneca with MedImmune, the company’s global biologics research and development arm and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Hakko Kirin Co., Ltd., Japan.
The WINDWARD programme in asthma is made up six Phase III trials, including SIROCCO, CALIMA, ZONDA, BISE, BORA and GREGALE. The two pivotal trials SIROCCO and CALIMA, are randomised, double-blinded, parallel-group, placebo-controlled trials designed to evaluate the efficacy and safety of a regular, subcutaneous administration of Fasenra (fixed 30mg dose) for up to 56-weeks in exacerbation-prone adult and adolescent patients 12 years of age and older.
A total of 2,510 patients (1,204 in SIROCCO and 1,306 in CALIMA) received standard-of-care medicines (including high-dosage inhaled corticosteroids and long-acting beta2-agonists) and were randomised globally to receive either Fasenra 30mg every 4-weeks; Fasenra 30mg every 4-weeks for the first three doses followed by 30mg every 8-weeks; or placebo administered via subcutaneous injection using an accessorised pre-filled syringe.
In SIROCCO and CALIMA, patients with severe, uncontrolled eosinophilic asthma receiving Fasenra experienced a significant reduction in asthma exacerbations and improvement in their lung function and asthma symptoms compared to patients receiving placebo, on top of their standard medicines. The most commonly reported adverse reactions during treatment were headache (8%) and pharyngitis (3%). Other common adverse reactions included fever, hypersensitivity reactions and injection site reactions.
A pooled post-hoc analysis of the SIROCCO and CALIMA trials, demonstrated an association between enhanced Fasenra efficacy and certain easily identifiable clinical features of severe eosinophilic asthma, including baseline blood eosinophil counts, history of more frequent exacerbations, chronic OCS use and a history of nasal polyposis.23
The third registrational trial, ZONDA, demonstrated a statistically-significant and clinically-meaningful reduction in daily-maintenance OCS use compared with placebo for patients with severe, uncontrolled OCS-dependent eosinophilic asthma receiving Fasenra. The results were published in the New England Journal of Medicine in May 2017.
In addition to WINDWARD, the Phase III VOYAGER programme is currently underway, which is evaluating the efficacy and safety of Fasenra in patients with severe COPD.