資料來源：https://www.prnewswire.com/news-releases/fasenra-benralizumab-receives-us-fda-approval-for-severe-eosinophilic-asthma-300556129.html

AstraZeneca and its global biologics research and development arm, MedImmune, today announced that the US Food and Drug Administration (FDA) has approved FASENRA™ (benralizumab) for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. FASENRA is not approved for the treatment of other eosinophilic conditions or relief of acute bronchospasm or status asthmaticus.

Pascal Soriot, Chief Executive Officer of AstraZeneca, said: "We're excited to offer FASENRA as a new precision biologic to help improve the lives of severe asthma patients whose disease is driven by eosinophilic inflammation. This is the first approval from our respiratory biologics portfolio and the latest in a series of significant milestones for our company as we deliver on our pipeline-driven transformation."

The FDA approval is based on results from the WINDWARD program, including the pivotal Phase III exacerbation trials, SIROCCO and CALIMA, and the Phase III oral corticosteroid (OCS)-sparing trial, ZONDA. Results for the 8-week benralizumab dosing regimen from these trials showed:

• Up to 51% reduction in the annual asthma exacerbation rate (AAER) versus placebo
• Significant improvement in lung function as measured by forced expiratory volume in one second (FEV₁) of up to 159 mL versus placebo. Differences were seen as early as 4 weeks after the first dose, providing an early indication of effectiveness 
• 75% median reduction in daily OCS use and discontinuation of OCS use in 52% of eligible patients
• An overall adverse event profile similar to that of placebo. Adverse events with an incidence greater than or equal to 3% were headache, pyrexia, pharyngitis and hypersensitivity reactions 

Eugene R. Bleecker, MD, Professor and Co-Director, Genetics, Genomics and Precision Medicine, University of ArizonaHealth Sciences, and lead investigator of the pivotal Phase III SIROCCO study, said: "This is an important day for severe, eosinophilic asthma patients who have had limited treatment options for far too long, with many relying on oral steroids to manage their symptoms. FASENRA has a strong clinical profile which includes the ability to show lung function improvement after the first dose, the potential to reduce – or even stop – oral steroid use, and the convenience of 8-week dosing. FASENRA also treats a distinct patient phenotype, helping physicians select the right patient in clinical practice with more confidence."

FASENRA is the only respiratory biologic that provides direct, rapid and near-complete depletion of eosinophils within 24 hours, as observed in a Phase II study. Eosinophils are a type of white blood cell that are a normal part of the body's immune system. 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.

FASENRA binds directly to the IL-5α receptor on an eosinophil and uniquely attracts natural killer cells to induce apoptosis (programmed cell death).  FASENRA will be available as a subcutaneous injection via a prefilled syringe administered once every 4 weeks for the first 3 doses, and then once every 8 weeks thereafter.  

Karen Kempley, severe, eosinophilic asthma patient, said: "Most people don't appreciate the simple act of breathing until they can't do it. As someone with severe asthma, I know how devastating it is to not have control over your asthma and to live with the fear of not knowing when your next asthma attack might happen. When you can't breathe, you can't do the things you want or need to do – like go to work or be with your family – and that impacts every aspect of your life."

FASENRA will be available in the US within the coming weeks. AstraZeneca recognizes patients may need assistance accessing FASENRA. FASENRA360 provides a range of support services for patients on FASENRA including access and reimbursement support, affordability programs for eligible patients, nursing support for FASENRA questions, and ongoing patient education. Eligible commercially insured patients may pay as little as $0 for FASENRA and as little as $0 for its injection administration.  

On November 10, 2017, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the marketing authorization of benralizumab. Benralizumab is also under regulatory review in Japan and several other countries.

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

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 ≥ 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.