BATTLE TESTED IN SEA: EXPLORE THE STUDIES

NUCALA has a strong foundation of evidence

Numerous studies

The evidence for NUCALA efficacy and safety is based on the results of numerous studies,1-7,11 including Trial 2 (pivotal exacerbation reduction trial) and Trial 3 (pivotal OCS reduction trial).

Trial 2: pivotal exacerbation reduction trial1,6

  • Trial 2: Study design, description, primary endpoint, and baseline characteristics

    Trial 2 (MENSA) study design infographic detailing the run-in period, treatment period with the various subgroups, and the follow-upTrial 2 (MENSA) study design infographic detailing the run-in period, treatment period with the various subgroups, and the follow-up

    Description of Trial 2: 32-week, multicenter, randomized, double-blind, double-dummy, placebo-controlled study comparing treatment with NUCALA or mepolizumab 75 mg IV to placebo, each added to SOC, in 576 patients ≥12 years of age with severe eosinophilic asthma (SEA).

    Select inclusion criteria1,7:

    • Blood eosinophil counts of ≥150 cells/µL at baseline or ≥300 cells/µL within the last 12 months
    • ≥2 exacerbations* in the previous year
    • High-dose ICS† plus additional controller(s) with or without OCS

    Primary endpoint: Exacerbations*/year for NUCALA vs placebo, 0.83 vs 1.74, 53% reduction (P<0.001).

    *Defined as worsening of asthma requiring: systemic corticosteroids or hospitalization or ED visit; or at least double the existing maintenance systemic corticosteroid dose for ≥3 days.
    †High-dose ICS defined as ≥880 μg of FP, or the equivalent, per day in patients ≥18 years of age, and ≥440 μg of FP, or the equivalent, per day in patients 12 to 17 years of age.6

    BASELINE CHARACTERISTICS OF PATIENTS IN TRIAL 21,6

    Data are mean values unless otherwise stated.

    Baseline Characteristic NUCALA (n=194) Placebo (n=191)
    Mean age 51 years 49 years
    Female 60% 56%
    Body mass index‡ 27.6 28.0
    Duration of asthma 20.5 years 19.5 years
    Use of oral glucocorticoids    
    Maintenance use 27% 23%
    Mean daily dose§ 12.6 mg 15.1 mg
    Allergic rhinitis 49% 50%
    Nasal polyposis  14% 17%
    FEV1    
    Before bronchodilationll 1.73 L 1.86 L
    Predicted value before bronchodilation 59.3% 62.4%
    Reversibility 27.9% 27.4%
    FEV1/FVC ratio 63% 64%
    ACQ-5 score# 2.26 2.28
    SGRQ score** 47.9 46.9
    Geometric mean IgE on loge scale 150 U/mL 150 U/mL
    Geometric mean blood eosinophil count on loge scale 290 cells/μL 320 cells/μL
    Asthma exacerbations    
    Severe episodes in previous year 3.8 3.6
    Necessitating hospitalization in the previous year 17% 18%

    ‡Body mass index is the weight in kilograms divided by the square of the height in meters.
    §The listed value is the prednisone equivalent.
    llReversibility was measured at baseline.
    The percent of predicted value before bronchodilation was assessed at the screening visit.
    #Scores on the ACQ range from 0 to 6 with higher scores indicating worse control; a change of 0.5 points is the minimal clinically important difference.12
    **Scores on the SGRQ range from 0 to 100 with higher scores indicating worse function; a change of 4 points is considered to be clinically relevant.13,14
    ACQ=Asthma Control Questionnaire; ED=emergency department; FEV1=forced expiratory volume in 1 second; FP=fluticasone propionate; FVC=forced vital capacity; ICS=inhaled corticosteroid; IgE=immunoglobulin E; IV=intravenous; OCS=oral corticosteroid; SC=subcutaneous; SGRQ=St. George’s Respiratory Questionnaire; SOC=standard of care.

Trial 3: pivotal OCS reduction trial2

  • Trial 3: Study design, description, and primary endpoint

    Trial 3 (SIRIUS) study design infographic detailing the run-in period, treatment period with the various subgroups, and the follow-upTrial 3 (SIRIUS) study design infographic detailing the run-in period, treatment period with the various subgroups, and the follow-up

    Description of Trial 3: 24-week, multicenter, randomized, double-blind, placebo-controlled study comparing treatment with NUCALA to placebo in 135 patients ≥12 years of age with severe eosinophilic asthma (SEA) requiring daily OCS in addition to regular use of high-dose ICS* plus an additional controller. Patients were not required to have a history of exacerbations in the previous 12 months.

    Select inclusion criteria:

    • Blood eosinophil counts of ≥150 cells/µL at baseline or ≥300 cells/µL within the last 12 months
    • Treatment with 5 mg to 35 mg of prednisone or its equivalent per day in addition to regular use of high-dose ICS* plus an additional controller

    Primary endpoint: Percent reduction in daily OCS dose (Weeks 20-24) while maintaining asthma control. NUCALA reduced daily OCS dose while maintaining asthma control vs placebo (P=0.008).

    *High-dose ICS defined as ≥880 μg of FP, or the equivalent, per day in patients ≥18 years of age, and ≥440 μg of FP, or the equivalent, per day in patients 12 to 17 years of age.6
    FP=fluticasone propionate; ICS=inhaled corticosteroid; OCS=oral corticosteroid; SOC=standard of care.

REALITI-A: real-world study6,7

  • REALITI-A: Study description, primary/secondary objectives, safety, and baseline characteristics

    Real-world studies are designed to evaluate associations among variables and not to definitively establish causality. Limitations important when interpreting results: no comparator arm; differences in patient populations and data collection vs randomized controlled trials.

    Description6,7: 2-year, global, single-arm, prospective, cohort study assessing the real-world effectiveness and safety of NUCALA 100 mg every 4 weeks in 822 adult patients with severe eosinophilic asthma (SEA) who met the eligibility requirements to initiate NUCALA. Data were collected prospectively at usual asthma healthcare visits. A 1-year period of relevant medical data was required prior to enrollment and was collected retrospectively at enrollment from medical records and patient recall for the previous year. Baseline visit was first administration of NUCALA.

    Enrollment requirements: Patients had to meet eligibility requirements for NUCALA initiation; 1-year period of relevant medical data that could be collected retrospectively.

    Study objectives: Assessed NUCALA 1-year or 2-year post-exposure period vs pre-NUCALA 1-year pre-exposure period (baseline).*

    Primary objective: Exacerbation† rate with NUCALA (1-year post-exposure) vs pre-NUCALA (1-year pre-exposure): 1.24/year vs 4.29/year, 71% reduction; rate ratio 0.29 (95% CI: 0.26, 0.32). Results are descriptive.

    Secondary objectives: Exacerbation† rate at 2 years post-exposure; exacerbations† requiring hospitalization and/or ED visit; and maintenance OCS use among baseline OCS-dependent subgroup.

    Discontinuations at 2 years (N=822): 27% discontinued NUCALA treatment (2% due to an AE; 9%, lack of reported efficacy; 15%, other).

    AEs in safety population (N=823): Any drug-related AE, 11%; serious AE, <1%. Most common AE reported was headache, 4%.

    BASELINE CHARACTERISTICS OF PATIENTS IN REALITI-A6

    Data are mean values unless otherwise stated.

    Baseline Characteristic Total Population
    (N=822)
    Age (range) 54 (17-89) years
    Geography (n)  
         Europe 665
         Canada 57
         United States 100
    Duration of asthma (n=801) 19.7 years  
    Geometric mean blood eosinophils (n=614) 350 cells/μL 
    Mean total IgE (n=674) 169 kU/L 
    Mean FeNO (n=360) 38 ppb 
    Allergic status‡ (n):  
         Positive 421
         Negative 51
    Current maintenance OCS use 39% 
    Median maintenance OCS dose among current users (n=297) 10.0 mg/day
    Prebronchodilator % predicted FEV1 (n=398) 67.7% 
    Exacerbations in prior year (n=821) 4.3 
    Exacerbations in prior year requiring hospitalization or ED visit (n=821) 1.0  
    ACQ-5 score (n=781) 2.88 
    Comorbidities (≥25%)    
          Allergic rhinitis 49%
          Chronic sinusitis 40%
          Nasal polyps 39%
    Gastroesophageal reflux disease 38%
          Drug hypersensitivity 33%
          Nasal polypectomy 28%

    *1-year pre-exposure rate based on 1-year analysis model.
    †Defined as worsening of asthma requiring: systemic corticosteroids or hospitalization or ED visit; or at least double the existing maintenance systemic corticosteroid dose for ≥3 days.
    ‡Allergic (atopic) status was determined by a positive skin prick test or positive RAST score ≥1 (≥0.35 kU/L) for ≥1 specific IgE allergen.
    ACQ=Asthma Control Questionnaire; AE=adverse event; CI=confidence interval; ED=emergency department; FEV1=forced expiratory volume in 1 second; FVC=forced vital capacity; OCS=oral corticosteroid; ppb=parts per billion.

COLUMBA: 4.5-year open-label study5,6

  • 4.5-year open-label study: Study design, description, and primary/secondary endpoints

    4.5-year open-label study design4.5-year open-label study design

    Description: 4.5-year, multicenter, open-label, long-term study assessing the safety, immunogenicity, and efficacy of NUCALA in 347 patients ≥12 years of age with severe eosinophilic asthma (SEA) previously treated in Trial 1 at least 12 months prior and who met eligibility criteria. All patients received NUCALA 100 mg SC added to asthma controller therapy.

    Primary endpoints: Long-term safety, including AEs, SAEs, and immunogenicity. Most frequent AEs (≥20%) were viral upper respiratory tract infection, 49%; headache, 29%; asthma,* 27%; upper respiratory tract infection, 23%; bronchitis, 21%. Two SAEs occurred in ≥1% of patients: asthma, 10%; and pneumonia, 2%. A total of 8% of patients had a positive anti-drug antibody result, but all were negative for neutralizing antibodies.

    Secondary endpoints: Results are descriptive.

    • Annualized exacerbation rate†: 0.68 (95% CI: 0.60, 0.78)
    • Asthma control: mean change from baseline in ACQ-5 score was –0.47 points at both Week 12 and end of study
    • Lung function: mean change from baseline in pre-bronchodilator FEV1 at Week 12 was 124 mL, and gradually declined to approximate baseline values at end of study

    Trial 111
    52-week dose-ranging exacerbation study comparing mepolizumab IV to placebo IV added to SOC in 616 patients ≥12 years of age with severe asthma. Primary endpoint: Exacerbations/year with mepolizumab 75 mg vs placebo, 1.24 vs 2.40, 48% reduction (P<0.0001).

    *Asthma reported as an AE means worsening or exacerbation of asthma.
    †Defined as worsening of asthma requiring: systemic corticosteroids or hospitalization or ED visit; or at least double the existing maintenance systemic corticosteroid dose for ≥3 days.
    ACQ=Asthma Control Questionnaire; AE=adverse event; CI=confidence interval; ED=emergency department; FEV1=forced expiratory volume in 1 second; IV=intravenous; SAE=serious adverse event; SC=subcutaneous; SOC=standard of care.

COSMOS: open-label extension study3

  • COSMOS: Study design, description, and primary endpoint

    COSMOS study designCOSMOS study design

    Description: 52-week, multicenter, open-label extension study assessing the safety and efficacy of NUCALA in 651 patients ≥12 years of age with SEA who completed Trial 2 or Trial 3. All patients in the 1-year open-label study received NUCALA added to SOC regardless of their previous treatment allocation (NUCALA, mepolizumab 75 mg IV, or placebo).

    SOC therapy: Regular treatment with high-dose ICS* plus an additional controller(s) with or without OCS.6

    Primary endpoints/results: Long-term safety, including AEs and SAEs. Most frequent AEs (≥10%): nasopharyngitis, 30%; upper respiratory infection, 16%; asthma,† 14%; headache, 14%; bronchitis, 12%; sinusitis, 10%. The only SAE that occurred in ≥1% of patients: asthma.†

    *High-dose ICS defined as ≥880 μg of FP, or the equivalent, per day in patients ≥18 years of age, and ≥440 μg of FP, or the equivalent, per day in patients 12 to 17 years of age.6
    †Asthma reported as an AE means worsening or exacerbation of asthma.

    AE=adverse event; FP=fluticasone propionate; ICS=inhaled corticosteroid; IV=intravenous; OCS=oral corticosteroid; SAE=serious adverse event; SEA=severe eosinophilic asthma; SOC=standard of care.

MUSCA: phase 3b quality of life trial4

  • MUSCA: Study design, description, and primary endpoint

    Description: 24-week, multicenter, randomized, double-blind, placebo-controlled study comparing treatment with NUCALA to placebo, each added to SOC, in 551 patients ≥12 years of age with SEA.

    Select inclusion criteria:

    • Blood eosinophil counts of ≥150 cells/µL at baseline or ≥300 cells/µL within the last 12 months
    • Patients aged ≥12 years

    SOC therapy: Regular treatment with high-dose ICS* plus an additional controller(s) with or without OCS6

    Primary endpoint/results: Mean change from baseline in SGRQ total score at Week 24: −15.6 for NUCALA vs −7.9 for placebo; treatment difference of −7.7 (P<0.0001). The improvement in both treatment arms was clinically meaningful.†

    *High-dose ICS defined as ≥880 μg of FP, or the equivalent, per day in patients ≥18 years of age, and ≥440 μg of FP, or the equivalent, per day in patients 12 to 17 years of age.6
    †Defined as a reduction in score of 4 points or more for minimal clinically important difference.14

    FP=fluticasone propionate; ICS=inhaled corticosteroid; OCS=oral corticosteroid; SEA=severe eosinophilic asthma; SGRQ=St. George’s Respiratory Questionnaire; SOC=standard of care.

6.4-year open-label study: long-term access6

  • 6.4-year open-label study: Study design, description, study objectives, and safety objectives

    6.4 year, open label study design graphic

    Description:

    Multicenter, open-label, long-term access study of add-on NUCALA every 4 weeks in 514 patients aged ≥6 years with SEA who met eligibility criteria and were enrolled within 6 months following a prior NUCALA study.

    Study objectives:

    • Provide mechanism to supply NUCALA to eligible patients who previously participated in GSK clinical studies with NUCALA
    • Safety objective: Collect additional safety data

    Serious AEs:

    • Reported in >1% of patients: worsening of asthma (3%)

    Non-serious AEs:

    • Reported in ≥10% of patients: worsening of asthma (30%), lower respiratory tract infection (11%), and headache (10%)

    *MUSCA: placebo-controlled study (N=551, 24 weeks) in patients aged ≥12 years.4

    †OSMO: open-label study (N=145, 32 weeks) in patients aged ≥12 years.8

    ‡COLUMBA: open-label long-term safety study (N=347; up to 4.5 years) in patients ≥12 years of age previously treated in Trial 1.5

    §COSMEX: open-label extension study (N=339, up to 3.3 years) in select patients from COSMOS, an open-label extension study (N=651, 52 weeks) following MENSA or SIRIUS.3,15

    ||COMET: placebo-controlled study (N=295, 52 weeks) in patients from COLUMBA and COSMEX.16

    200363: open-label study (N=36, 52 weeks) in patients aged 6-11 years.9,10

    AE=adverse event; SAE=serious adverse event; SC=subcutaneous; SEA=severe eosinophilic asthma; SOC=standard of care.

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