FASENRA (benralizumab) Shows Consistent Safety and Sustained Efficacy in Long-Term Phase III BORA Trial in Severe Eosinophilic Asthma

Business Wire 18-Sep-2018 7:00 AM

74% of continuously-treated patients with a blood eosinophil count 300 or greater were exacerbation-free in the second year of treatment

Data presented at the European Respiratory Society (ERS) International Congress 2018

AstraZeneca today announced results from the Phase III extension BORA trial evaluating the long-term safety and efficacy of FASENRA™ (benralizumab) as an add-on maintenance treatment in patients with severe eosinophilic asthma who had previously completed one of the two pivotal SIROCCO or CALIMA Phase III trials.

In the BORA trial, FASENRA given for an additional 56 weeks showed a safety and tolerability profile similar to that observed in the placebo-controlled SIROCCO and CALIMA trials, with no increase in the frequencies of overall or serious adverse events. The improvements in efficacy measures observed with FASENRA in the SIROCCO or CALIMA trials were maintained over the second year of treatment. Patients who were treated with placebo in the SIROCCO and CALIMA trials and subsequently transitioned to FASENRA in the BORA trial experienced improvements in efficacy outcomes consistent with those observed for FASENRA-treated patients in the previous trials. FASENRA is not approved for the treatment of other eosinophilic conditions or relief of acute bronchospasm or status asthmaticus.

74% of patients with a baseline blood eosinophil count of 300 cells per µL or greater (the primary efficacy population in the Phase III trials) who received FASENRA every eight weeks continuously from SIROCCO or CALIMA and into BORA, were exacerbation-free in BORA in their second year of treatment and maintained improvements in lung function and asthma control.

65% and 66%, respectively, of patients with a baseline blood eosinophil count of 300 cells per µL or greater who received FASENRA 30 mg every eight weeks were exacerbation-free their first year of treatment in the one-year, predecessor SIROCCO and CALIMA trials (49% for placebo arms in both trials).

The BORA data will be presented today during a late-breaking oral session at the European Respiratory Society (ERS) International Congress 2018 in Paris, France.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: "The BORA data are important news for patients with severe eosinophilic asthma who need a treatment with sustained efficacy to help control their disease, and with a safety profile that supports long-term use."

Dr. William Busse, Professor of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, and lead investigator on BORA, said: "As a clinician, I am excited by the BORA trial results, which provide confidence to patients with severe eosinophilic asthma and physicians that the positive outcomes they are seeing with FASENRA can be maintained over a second year of treatment. In FASENRA, we have a biologic treatment that can improve outcomes for these patients long-term."

The overall annual asthma exacerbation rate for patients with baseline blood eosinophil counts of 300 cells per µL or greater who received FASENRA every 8 weeks continuously was consistent with the predecessor SIROCCO and CALIMA trials (0.46 in BORA; 0.65 and 0.66 in SIROCCO and CALIMA, respectively). Overall improvements in lung function, asthma control, asthma-related and general health-related quality of life scores were maintained for patients who received FASENRA continuously and were improved for patients previously receiving placebo in SIROCCO or CALIMA. Near complete eosinophil depletion was maintained in patients who continuously received FASENRA.

The most commonly-reported adverse events (= 5%) in BORA were upper respiratory tract infection, worsening asthma, headache, bronchitis and acute sinusitis. The most commonly-reported adverse events in SIROCCO, CALIMA and ZONDA (= 5%) were headache and pharyngitis.

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

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Known hypersensitivity to benralizumab or excipients.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

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.

ADVERSE REACTIONS

The most common adverse reactions (incidence > to 5%) include headache and pharyngitis. Injection site reactions (e.g., 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.

INDICATION

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

Please read full Prescribing Information, including Patient Information.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

NOTES TO EDITORS

About Severe Asthma

Asthma affects approximately 26 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 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 socio-economic burden of severe, uncontrolled asthma with these patients accounting for 50% of asthma-related costs despite compromising 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.

About FASENRA

FASENRA is a monoclonal antibody that binds directly to the IL-5a 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 hyper-responsiveness, 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 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 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.

About the BORA Trial

BORA is one of the six Phase III trials in the FASENRA WINDWARD program in asthma, which also includes SIROCCO, CALIMA, ZONDA, BISE and GREGALE. BORA is a randomized, double-blind, parallel-group, Phase III extension trial of patients who had completed one of the three pivotal Phase III trials, SIROCCO, CALIMA or ZONDA. The current analysis includes results for 1926 patients from the two placebo controlled exacerbation trials, SIROCCO (48 week) and CALIMA (56 week). Patients continued add-on treatment with subcutaneous FASENRA 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W; first three doses 4 weeks apart) or, for patients previously receiving placebo, were re-randomized 1:1 to either Q4W or Q8W.

Once the BORA target enrollment had been achieved, adult patients who wanted to continue treatment for a longer period of time had the option to continue therapy in an additional open-label, long term extension trial, without completing the full, planned follow up in BORA. Approximately half of patients in the shorter (28 weeks) and smaller ZONDA study went into an additional extension trial without completing the planned 56-week treatment period in BORA. Therefore, ZONDA patients were not included in this BORA analysis, and will be reported separately according to the analysis plan.

Additional analyses from the BORA trial, including treatments in adolescents up to 108 weeks, will be available in the second half of 2019.

About AstraZeneca in Respiratory Disease

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 2017. 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 pressurized 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-IL-5r?), now approved for severe eosinophilic asthma and in development for severe nasal polyposis, and tezepelumab (anti-TSLP), which is in Phase III trials and achieved its Phase IIb primary and secondary endpoints. AstraZeneca's research is focused on addressing underlying disease drivers focusing on the lung epithelium, lung immunity and lung regeneration.

About AstraZeneca

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 main therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. 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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