TARGET EOSINOPHILS IN SEVERE ASTHMA WITH ANTI-IL-5 THERAPY

How NUCALA targets eosinophils

Diagram of anti-IL-5 mechanism of action of NUCALA on blood eosinophils for the treatment of severe eosinophilic asthma

The MOA of NUCALA in asthma has not been definitively established.

  • IL-5 binds to complex on EOS

    Interleukin-5 (IL-5) is the major cytokine responsible for eosinophil growth, activation, and survival. IL-5 binds to the IL-5 receptor complex (IL-5R) expressed on the eosinophil cell surface.

  • How IL-5 impacts EOS

    Downstream signaling by IL-5 promotes the growth and differentiation, recruitment, activation, and survival of eosinophils.

  • NUCALA targets IL-5

    NUCALA, a humanized monoclonal antibody, targets IL-5 and binds to it. NUCALA blocks IL-5 binding to the alpha chain of the IL-5 receptor complex.

  • How NUCALA reduces EOS

    NUCALA inhibits IL-5 signaling, reducing the production and survival of eosinophils.

  • transcript

    TEXT ONSCREEN:

    [NUCALA Logo] NUCALA (mepolizumab) Injection 100 mg/mL

    MECHANISM OF ACTION VIDEO

    The mechanism of action of mepolizumab in asthma has not been definitively established.

    TEXT ONSCREEN:

    NUCALA is indicated for the add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma and with an eosinophilic phenotype.

    NUCALA is not indicated for the relief of acute bronchospasm or status asthmaticus.

    NUCALA should not be administered to patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.

    Please review Important Product Information for NUCALA near the end of this video.

    Please see full Prescribing Information for NUCALA at NucalaHCP.com.

    MALE NARRATOR:

    NUCALA is indicated for the add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma and with an eosinophilic phenotype.

    NUCALA is not indicated for the relief of acute bronchospasm or status asthmaticus.

    TEXT ONSCREEN:

    Eosinophils

    IL-5

    IL-5R alpha

    IL-5R beta common

    Intracellular downstream signaling

    WOMAN NARRATOR:

    Inflammation, an important component of asthma pathogenesis, is mediated by multiple cell types, including eosinophils.

    Eosinophilic inflammation can be reproducibly characterized by blood eosinophil counts.

    Interleukin 5 (IL-5), a major cytokine responsible for eosinophil development, binds to the IL-5 receptor complex expressed on the eosinophil surface.

    Downstream signaling promotes the growth and differentiation, recruitment, activation, and survival of eosinophils.

    TEXT ONSCREEN:

    [NUCALA Logo] NUCALA (mepolizumab) Injection 100 mg/mL

    The mechanism of action of mepolizumab in asthma has not been definitively established.

    WOMAN NARRATOR:

    Mepolizumab is a humanized monoclonal antibody that targets human IL-5 with high affinity and specificity.

    The mechanism of action of mepolizumab in asthma has not been definitively established.

    TEXT ONSCREEN:

    Mepolizumab

    IL-5

    IL-5R alpha

    WOMAN NARRATOR:

    Mepolizumab binds to IL-5, blocking its binding to the alpha chain of the IL-5 receptor complex. This inhibits IL-5 signaling, reducing the production and survival of eosinophils.

    TEXT ONSCREEN:

    IMPORTANT PRODUCT INFORMATION

    May cause hypersensitivity reactions (eg, anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash). Herpes zoster has occurred. Do not stop systemic/inhaled corticosteroids abruptly. Treat pre-existing helminth infections before starting NUCALA. Most common adverse reactions: headache, injection site reactions, back pain, fatigue.

    Please see full Prescribing Information for NUCALA at NucalaHCP.com.

    MALE NARRATOR:

    NUCALA may cause hypersensitivity reactions, such as anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, and rash.

    Herpes zoster has occurred. Consider vaccination if medically appropriate.

    Do not stop systemic or inhaled corticosteroids abruptly.

    Treat pre-existing helminth infections before starting NUCALA.

    Most common adverse reactions were headache, injection site reactions, back pain, and fatigue.

    TEXT ONSCREEN:

    IMPORTANT PRODUCT INFORMATION (cont’d)

    To report SUSPECTED ADVERSE REACTIONS, contact GSK at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    Please see full Prescribing Information for NUCALA at NucalaHCP.com.

    MALE NARRATOR:

    Please see full Prescribing Information for NUCALA at NucalaHCP.com.

    TEXT ONSCREEN:

    1. NUCALA [package insert]. Durham, NC: GSK; 2023.

    2. Katz LE, Gleich GJ, Hartley BF, Yancey SW, Ortega HG. Blood eosinophil count is a useful biomarker to identify patients with severe eosinophilic asthma. Ann Am Thorac Soc. 2014;11(4):531-536. 

    3. Hancox J, Pavord ID, Sears MR. Associations between blood eosinophils and decline in lung function among adults with and without asthma. Eur Respir J. 2018;51(4):1702536.

    4. Trivedi SG, Lloyd CM. Eosinophils in the pathogenesis of allergic airways disease. Cell Mol Life Sci. 2007;64(10):1269-1289. 

    5. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):651-659.

    All animations are represented under a licensing agreement with all rights granted for GSK use.

    TEXT ONSCREEN:

    [NUCALA Logo] NUCALA (mepolizumab) Injection 100 mg/mL

    Trademarks are owned by or licensed to the GSK group of companies.
    [GSK logo]

    ©2023 GSK or licensor.

    MPLVID230017 September 2023

    Produced in USA.

View the NUCALA MOA

Mechanism of action | 2:14

Watch this illustration of the mechanism of action (MOA) of NUCALA (mepolizumab) in asthma.

What role do blood eosinophils play?

Eosinophils play a role in maintaining health, which includes regulating the immune system, regenerating and repairing tissue, and host protection (eg, defending the body against parasitic infection).1 In severe asthma, however, too many eosinophils are a key driver of asthma pathophysiology, including airway inflammation.2,3

Cell diagram representing the key role of eosinophils in health maintenance, but when in excessive amounts they are a key driver of asthma pathophysiology Cell diagram representing the key role of eosinophils in health maintenance, but when in excessive amounts they are a key driver of asthma pathophysiology

As shown here, the majority of patients with severe asthma had evidence of an eosinophilic phenotype.4*

Infographic showing that the reported prevalence of patients with severe asthma who most likely have eosinophilic asthma was 74%-84%

  • *See how 84% and 74% were identified in ISAR

    International Severe Asthma Registry: 84% of adults identified as “most likely” to have an eosinophilic phenotype in prospective analysis (N=1716) using a predefined algorithm of ≥1: blood EOS count ≥300 cells/μL; on anti-IL-5/5R therapy; blood EOS count of ≥150-300 cells/μL on maintenance OCS; or ≥2: nasal polyps, elevated FeNO, late-onset asthma. 74% identified in retrospective analysis of medical records in the US (n=1891).4

    


    FeNO=fractional exhaled nitric oxide; IL-5=interleukin-5; IL-5R=interleukin-5 receptor.

NUCALA reduced blood EOS levels and maintained them within normal levels

4.5-YEAR OPEN-LABEL STUDY5,6

Graph showing an 80% reduction in blood eosinophils over the 4.5 year clinical trial period Graph showing an 80% reduction in blood eosinophils over the 4.5 year clinical trial period

Mean blood EOS levels: 240 cells/μL at baseline; ~40-50 cells/μL on NUCALA treatment.6

Results are descriptive. The clinical significance of these pharmacodynamic data is unknown.

  • See data on normal EOS levels

    Mean normal blood EOS levels have been reported as 100 cells/μL (range: 34 to 257) and 107 cells/μL (5th, 95th percentile: 30, 395) in a general population of subjects without confounding factors; EOS levels vary based on age, sex, environmental exposures, and comorbid conditions.7,8

4.5-year open-label study design & primary endpoint (safety)

Eosinphilic inflammation

In patients with SEVERE ASTHMA, too many airway tissue EOSINOPHILS is associated with9,10:

  • Increased SYMPTOMS
  • Greater likelihood of EXACERBATIONS
  • Airway INFLAMMATION
Exacerbation risk

EXACERBATION RISK IN PATIENTS WITH SEVERE UNCONTROLLED ASTHMA11†

  • Greater blood eosinophil count was predictive of exacerbation risk
  • Serum IgE level ± atopy was not predictive of exacerbation risk

†Pooled analysis of 2016 adult and adolescent patients randomized to receive placebo across 7 multicenter, randomized, double-blind, placebo-controlled trials with asthma biologics.11

Female with severe eosinophilic asthma (SEA) with frequent exacerbations

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