Interleukin-5 antagonists

Initial U.S. Approval:  2015

Mechanism of Action: Mepolizumab is an interleukin-5 antagonist (IgG1 kappa). IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Mepolizumab binds to IL-5 with a dissociation constant of 100 pM, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface. Inflammation is an important component in the pathogenesis of asthma. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. Mepolizumab, by inhibiting IL-5 signaling, reduces the production and survival of eosinophils; however, the mechanism of mepolizumab action in asthma has not been definitively established.

INDICATIONS AND USAGE:  NUCALA® is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. [See Clinical Studies (14).]

Limitations of Use
NUCALA is not indicated for treatment of other eosinophilic conditions.
NUCALA is not indicated for the relief of acute bronchospasm or status asthmaticus.

HOW SUPPLIED: For injection: 100 mg of lyophilized powder in a single-dose vial for reconstitution.

Anaphylaxis can be life-threatening. Patients should be observed for an appropriate period of time after CINQAIR administration by a healthcare professional prepared to manage anaphylaxis. Discontinue CINQAIR immediately if the patient experiences signs or symptoms of anaphylaxis

Initial U.S. Approval:  2016

Mechanism of Action:
Reslizumab is an interleukin-5 antagonist (IgG4, kappa). IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Reslizumab binds to IL-5 with a dissociation constant of 81 pM, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil surface. Inflammation is an important component in the pathogenesis of asthma. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. Reslizumab, by inhibiting IL-5 signaling, reduces the production and survival of eosinophils; however, the mechanism of reslizumab action in asthma has not been definitively established.

INDICATIONS AND USAGE:

CINQAIR is an interleukin-5 antagonist monoclonal antibody (IgG4 kappa) indicated for add-on maintenance treatment of patients with severe asthma aged 18 years and older, and with an eosinophilic phenotype.

Limitations of Use: CINQAIR is not indicated for:
•treatment of other eosinophilic conditions
•relief of acute bronchospasm or status asthmaticus.

DOSAGE AND ADMINISTRATION

•CINQAIR is for intravenous infusion only. Do not administer as an intravenous push or bolus ( 2.1)
•CINQAIR should be administered in a healthcare setting by a healthcare professional prepared to manage anaphylaxis ( 2.2)
•Recommended dosage regimen is 3 mg/kg once every 4 weeks by intravenous infusion over 20-50 minutes ( 2.1)

Discontinue the infusion immediately if the patient experiences a severe systemic reaction, including anaphylaxis
See package insert for comments regarding preparation of the infusion.

HOW SUPPLIED:
DOSAGE FORMS AND STRENGTHS
Injection: 100 mg/10 mL (10 mg/mL) solution in single-use vials