Benralizumab

FASENRA is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody (IgG1, kappa) indicated for: • add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma, and with an eosinophilic phenotype. • treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). • treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) without an identifiable non-hematologic secondary cause. Limitations of Use: Not for relief of acute bronchospasm or status asthmaticus.

Benralizumab is a humanized afucosylated, monoclonal antibody (IgG1, kappa) that directly binds to the alpha subunit of the human interleukin-5 receptor (IL-5Rα) with a dissociation constant of 11 pM. The IL-5 receptor is expressed on the surface of eosinophils and basophils. In an in vitro setting, the absence of fucose in the Fc domain of benralizumab facilitates binding (45.5 nM) to FcɣRIII receptors on immune effector cells, such as natural killer (NK) cells, leading to apoptosis of eosinophils and basophils through antibody-dependent cell-mediated cytotoxicity (ADCC). Inflammation is an important component in the pathogenesis of asthma, EGPA, and HES. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation.

Administer by subcutaneous injection. Asthma Adult and Pediatric Patients 12 Years of Age and Older: • Recommended dosage is 30 mg every 4 weeks for first 3 doses followed by once every 8 weeks thereafter. Pediatric Patients 6 Years to 11 Years of Age: • Weighing Less Than 35 kg: the recommended dosage is 10 mg every 4 weeks for first 3 doses followed by once every 8 weeks thereafter. • Weighing 35 kg or More: the recommended dosage is 30 mg every 4 weeks for first 3 doses followed by once every 8 weeks thereafter. EGPA and HES • Recommended dosage is 30 mg every 4 weeks. See full prescribing information for administration instructions of FASENRA prefilled syringe and FASENRA PEN.

FASENRA is contraindicated in patients who have known hypersensitivity to benralizumab or any of its excipients. Known hypersensitivity to benralizumab or excipients.

• Hypersensitivity reactions: Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA. Discontinue in the event of a hypersensitivity reaction. • Reduction in Corticosteroid Dosage: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. Decrease corticosteroids gradually, if appropriate. • Parasitic (Helminth) Infection: Treat patients with pre-existing helminth infections before therapy with FASENRA. If patients become infected while receiving FASENRA and do not respond to anti-helminth treatment, discontinue FASENRA until the parasitic infection resolves.

The following adverse reactions are described in greater detail in other sections: • Hypersensitivity Reactions Most common adverse reactions (incidence greater than or equal to 5%): • Asthma: headache and pharyngitis. • EGPA: headache. • HES: headache, hypersensitivity reactions, and influenza-like illness.

Store refrigerated at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. If needed, the prefilled syringe and autoinjector may be stored at room temperature up to 77°F (25°C) for a maximum of 14 days in the original carton to protect from light. Once removed from the refrigerator and brought to room temperature (up to 77°F [25°C]), the prefilled syringe and autoinjector must be used within 14 days or discarded. Do not freeze. Do not shake.