TARGET EOSINOPHILS IN COPD WITH AN ANTI-IL-5 THERAPY

How NUCALA targets eosinophils, a key driver of inflammation

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The mechanism of action of NUCALA in COPD has not been definitively established.

    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 COPD with an eosinophilic phenotype, however, too many eosinophils are a key driver of COPD pathophysiology, and are associated with greater risk of COPD exacerbations and airway inflammation.2-5

    In MATINEE, NUCALA reduced eosinophils at Week 4 and maintained throughout the treatment period6

    In MATINEE, NUCALA reduced eosinophils at Week 4 and maintained throughout the treatment periodIn MATINEE, NUCALA reduced eosinophils at Week 4 and maintained throughout the treatment period

    NUCALA ratio to screening: Week 4, 0.23; Week 104, 0.21.

    Mean blood eosinophil levels (NUCALA, placebo):

    • Screening: 480 cells/µL, 480 cells/µL
    • At Week 104: 60 cells/μL (n=94), 330 cells/μL (n=82)

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

    *SOC=triple inhaled therapy (ICS + LABA + LAMA).

    MATINEE/METREX study designs

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    EXPLORE NUCALA DATA IN COPD PATIENTS WITH AN EOSINOPHILIC PHENOTYPE

    SEE EFFICACY DATA

    CI=confidence interval; EOS=eosinophil; ICS=inhaled corticosteroid; IL-5=interleukin-5; IL-5R=interleukin-5 receptor; LABA=long-acting beta2-agonist; LAMA=long-acting muscarinic antagonist; LS=least squares; SCR=screening; SOC=standard of care.

    INDICATIONS & IMPORTANT SAFETY INFO

    INDICATIONS

    IMPORTANT SAFETY INFORMATION

    INDICATIONS

    NUCALA is indicated for the: 

    • add-on maintenance treatment of adult patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype. NUCALA is not indicated for the relief of acute bronchospasm.
    • 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.
    • add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adult patients aged 18 years and older with inadequate response to nasal corticosteroids.
    • 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) for greater than or equal to 6 months without an identifiable non-hematologic secondary cause. 

    IMPORTANT SAFETY INFORMATION

    CONTRAINDICATIONS

    Known hypersensitivity to mepolizumab or excipients.

     

    WARNINGS AND PRECAUTIONS

    Hypersensitivity Reactions

    Hypersensitivity reactions (eg, anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred with NUCALA. These reactions generally occur within hours of administration but can have a delayed onset (ie, days). Discontinue if a hypersensitivity reaction occurs.

     

    Acute Symptoms of Asthma or COPD or Acute Deteriorating Disease

    NUCALA should not be used to treat acute symptoms or acute exacerbations of asthma or COPD, or acute bronchospasm.

     

    Opportunistic Infections: Herpes Zoster

    Herpes zoster infections have occurred in patients receiving NUCALA. Consider vaccination if medically appropriate.

     

    Reduction of Corticosteroid Dosage

    Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with NUCALA. Decreases in corticosteroid doses, if appropriate, should be gradual and 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

    Treat patients with pre-existing helminth infections before initiating therapy with NUCALA. If patients become infected while receiving NUCALA and do not respond to anti-helminth treatment, discontinue NUCALA until infection resolves.

     

    ADVERSE REACTIONS

    Most common adverse reactions (≥5%):

    • Severe asthma trials: headache, injection site reaction, back pain, fatigue
    • CRSwNP trial: oropharyngeal pain, arthralgia
    • COPD trials: back pain, diarrhea, cough
    • EGPA and HES trials (300 mg of NUCALA): most common adverse reactions were similar to severe asthma

    Systemic reactions, including hypersensitivity, occurred in clinical trials in patients receiving NUCALA. Manifestations included rash, pruritus, headache, myalgia, flushing, urticaria, erythema, fatigue, hypertension, warm sensation in trunk and neck, cold extremities, dyspnea, stridor, angioedema, and multifocal skin reaction. A majority of systemic reactions were experienced the day of dosing.

     

    USE IN SPECIFIC POPULATIONS

    The data on pregnancy exposures are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as mepolizumab, are transported across the placenta in a linear fashion as the pregnancy progresses; therefore, potential effects on a fetus are likely to be greater during the second and third trimesters.

     

    Please see full Prescribing Information and Patient Information for NUCALA.

    PMUS-MPLWCNT250056 June 2025

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

    References

    1. Weller PF, Spencer LA. Functions of tissue-resident eosinophils. Nat Rev Immunol. 2017;17(12):746-760.

    2. David B, Bafadhel M, Koenderman L, De Soyza A. Eosinophilic inflammation in COPD: from an inflammatory marker to a treatable trait. Thorax. 2021;76(2):188-195

    3. Brightling C, Greening N. Airway inflammation in COPD: progress to precision medicine. Eur Respir J. 2019;52(2):1900651.

    4. Rabe KF, Rennard S, Martinez FJ, et al. Targeting type 2 inflammation and epithelial alarmins in chronic obstructive pulmonary disease: a biologics outlook. Am J Respir Crit Care Med. 2023;208(4):392-405.

    5. Maspero J, Adir Y, Al-Ahmad M, et al. Type 2 inflammation in asthma and other airway diseases. ERJ Open Res. 2022;8(3):00576-2021.

    6. Data on file, GSK.