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Explore the Nucala clinical data

Use the efficacy data sorter to explore key clinical information from the Nucala clinical trials in adult patients with severe refractory eosinophilic asthma.

Consistent exacerbation
reduction

Hospitalisation
reduction

Exacerbation reduction from 150 cells/μL

Long-term exacerbation reduction

Oral corticosteroid reduction

Safety & tolerability

DREAM study

MENSA study

SIRIUS study

COSMOS study

MUSCA study

OSMO Study Design

COLUMBA Study

OSMO Study Design

OSMO Study Design

Nucala consistently reduced frequency of clinically significant exacerbations vs. placebo across multiple studies*[1], [2]

Reduction in frequency of clinically significant exacerbations vs. placebo in MENSA and MUSCA studies*[1], [2]

MENSA: A 32-week randomised double-blind, double-dummy study.

MUSCA: A 24-week, randomised, double-blind, placebo-controlled, phase 3b study.

Access the full study information using the efficacy data sorter tabs above.

ICS, inhaled corticosteroids; ITT, Intention to Treat; SC, subcutaneous; SoC, standard of care.
*When both treatments were added to high-dose inhaled corticosteroids and additional maintenance treatment(s).
**MENSA study primary endpoint. 576 patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled corticosteroids.[1]
MUSCA study additional endpoint. 551 patients (ITT) with severe eosinophilic asthma and a history of 2+ exacerbations requiring treatment in the previous 12 months before screening despite regular use of high-dose inhaled corticosteroids plus other controller medicines.[2]


References:

  1. Ortega HG et al. N EnglJ Med 2014; 371:1198–1207.
  2. Chupp GL et al. Lancet Respir Med 2017; 5:390–400.

Nucala consistently reduced hospitalisations and/or ED visits resulting from exacerbations vs. placebo across multiple studies*[1], [2]

Reduction in exacerbations resulting in hospitalisation and/or ED visits vs. placebo in MENSA & MUSCA studies*[1], [2]

MENSA: A 32-week randomised double-blind, double-dummy study

MUSCA: A 24-week, randomised, double-blind, placebo-controlled, phase 3b study

Access the full study information using the efficacy data sorter tabs above.

ED, emergency department; ICS, inhaled corticosteroids; ITT, Intention to Treat; SC, subcutaneous; SoC, standard of care
*When both treatments were added to high-dose inhaled corticosteroids and additional maintenance treatment(s).
MENSA: 576 patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled corticosteroids.[1]
MUSCA: 551 patients (ITT) with severe eosinophilic asthma and a history of 2+ exacerbations requiring treatment in the previous 12 months before screening despite regular use of high-dose inhaled corticosteroids plus other controller medicines.[2]


References:

  1. Ortega HG et al. N EnglJ Med 2014; 371:1198–1207.
  2. Chupp GL et al. Lancet Respir Med 2017; 5:390–400.

Nucala consistently reduced exacerbations vs. placebo in patients with blood eosinophil counts as low as 150 cells/μL[1]

Data from all mepolizumab doses were combined for the analysis (75mg IV, 100mg SC).[1] Only 100mg SC Nucala is licensed for use.[2]

Reduction in frequency of clinically significant exacerbations vs. placebo by baseline blood eosinophil counts (MENSA study population)[1]

  • Nucala has shown clinically significant reduction in exacerbations in patients with blood eosinophil levels of ≥150 cells/μL and ≥2 exacerbations in the past year[1]
  • Nucala reduced exacerbations vs. placebo by 66% (0.89/year vs. 2.62/year; p=0.001) in patients with blood eosinophil levels of ≥300 cells/μL and ≥3 exacerbations in the past year[3]

MENSA: A 32-week randomised double-blind, double-dummy study

Access the full study information using the efficacy data sorter tabs above.

IV, intravenous; SC, subcutaneous; SoC, standard of care
MENSA: 576 patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled corticosteroids.[1]


References:

  1. Ortega HG et al. N EnglJ Med 2014; 371:1198–1207.
  2. Nucala Summary of Product Characteristics
  3. GlaxoSmithKline. Data on file: MEA115588.

Nucala reduced patients’ exacerbations vs. placebo for more than 1.5 years[1]

Data from all mepolizumab doses were combined for the analysis (75mg IV, 100mg SC).[1] Only 100mg SC Nucala is licensed for use.[2]

Durability of exacerbation reduction among patients enrolled from MENSA (post-hoc analysis)*[1]

Offer your patients the long-term assurance they need from a sustained efficacy profile

MENSA: A 32-week randomised double-blind, double-dummy study
COSMOS: A 52-week, open-label extension study

Access the full study information using the efficacy data sorter tabs above.

IV, intravenous; OL, open label; SC, sub-cutaneous
COSMOS: Patients with severe eosinophilic asthma who previously received mepolizumab or placebo in the 32-week MENSA or 24-week SIRIUS studies.[1]
MENSA: 576 patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled corticosteroids.[3]


References:

  1. Lugogo N et al. Clin Ther 2016; 38:2058–2070.
  2. Nucala Summary of Product Characteristics.
  3. Ortega HG et al. N Engl J Med 2014; 371:1198–1207.

Nucala reduced patients’ daily OCS dose for at least 1.5 years*[1]

Durability of OCS dose reduction from baseline among patients enrolled from SIRIUS (post-hoc analysis)*[1]

In SIRIUS, Nucala offered a:

  • Median percent reduction in daily OCS dose of 50% (range 20–75%) vs. 0% (range -20–33.3%) for patients on placebo** at Week 24 (p=0.007).[2] The only biologic for severe refractory eosinophilic asthma with proven effect for up 1.5 years[1]
    In the COSMOS open-label extension, Nucala offered a:
  • Daily OCS dose reduction that was sustained up to 1.5 years, with nearly a third of patients no longer taking OCS between Weeks 72 and 76[1]††

COSMOS: A 52-week, open-label extension study
SIRIUS: A 24-week randomised, double-blind trial

Access the full study information using the efficacy data sorter tabs above.

OL, open label; OCS, oral corticosteroids
*OCS dose reductions were based on investigator judgement in the COSMOS open label extension study.[1]
**When both treatments were added to high-dose ICS and additional maintenance treatment(s). (Nucala n=69, placebo n=66; median dose: 10.0mg/day vs. 12.5mg/day at baseline and 3.1mg/day vs. 10.0mg/ day at Weeks 20–24, respectively).[2], [3]
SIRIUS secondary endpoint.
††32% (18/57) and 28% (16/58) of patients previously on Nucala and placebo, respectively.[1]
SIRIUS study secondary endpoint. 135 patients with severe eosinophilic asthma.[2]
COSMOS study additional endpoint. Patients with severe eosinophilic asthma who previously received mepolizumab or placebo in the 32-week MENSA or 24-week SIRIUS studies. OCS dose reductions were based on investigator judgement.[1]

References:

  1. Lugogo N et al. Clin Ther 2016; 38:2058–2070.
  2. Bel EH et al. N EnglJ Med 2014; 371:1189–1197.
  3. Bel EH et al. N EnglJ Med 2014; 371:1189–1197. Supplementary information

Nucala gives confidence to you and your patients, with a safety profile established for at least 1.5 years[1]

Adverse reactions from the MENSA and SIRIUS placebo-controlled studies in patients receiving Nucala 100mg SC (n=263)[1]

Very common (≥1/10), common (≥1/100 to <1/10), rare (≥1/10,000 to <1/1,000)

  • The safety profile of Nucala in the 52-week open-label extension study was similar to the controlled asthma studies[2]
  • Nucala has a similar incidence of adverse events vs. placebo, with the exception of injection site reactions (8% for Nucala, 3% for placebo)††[1], [3-5]
  • Local injection site reactions occurred mainly at the start of treatment and within the first 3 injections, with fewer reports on subsequent injection[1]

Have the assurance of a consistent long-term safety profile when you prescribe Nucala

MENSA: A 32-week randomised double-blind, double-dummy study
SIRIUS: A 24-week randomised, double-blind trial

Access the full study information using the efficacy data sorter tabs above.

ICS, inhaled corticosteroids; SC, subcutaneous
*Systemic reactions, including hypersensitivity, have been reported at an overall incidence comparable to that of placebo.[1]
The most common manifestations associated with reports of systemic non-allergic administration related reactions were rash, flushing and myalgia; these manifestations were reported infrequently and in <1% of subjects receiving Nucala 100mg subcutaneously.[1]
**From spontaneous post-marketing reporting.[1]
††When both treatments were added to high-dose ICS and additional maintenance treatment(s).
MENSA. A 32-week, randomised, double-blind, double-dummy study of 576 patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled corticosteroids.[3]
SIRIUS. A 24-week randomised, double-blind trial of 135 patients with severe eosinophilic asthma.[3], [5]


References:

  1. Nucala Summary of Product Characteristics
  2. Lugogo N et al. Clin Ther 2016; 38:2058–2070.
  3. Ortega HG et al. N Engl J Med 2014; 371:1198–1207.
  4. Chupp GL et al. Lancet Respir Med 2017; 5:390–400.
  5. Bel EH et al. N Engl J Med 2014; 371:1189–1197.

DREAM was a dose-ranging and confirmatory study to evaluate the efficacy and safety of mepolizumab[1]

Population

The study included 616 patients aged 12–74 years, with a history of severe asthma exacerbations (two or more requiring systemic corticosteroid treatment in the previous 12 months) and evidence of eosinophilic inflammation as shown by one or more of the following criteria:[1]

  • Sputum eosinophil count of 3% or more
  • Exhaled nitric oxide concentration of 50 ppb or more
  • Asthma-related peripheral blood eosinophil count of ≥300 cells/μL
  • Prompt deterioration of asthma control after a ≤25% reduction in regular maintenance inhaled or oral corticosteroids (OCS)

Study design

DREAM (Dose Ranging Efficacy And safety with Mepolizumab) was a randomised, multicentre, double-blind, placebo-controlled, Phase IIb/III clinical trial that investigated the efficacy and safety of mepolizumab in patients with severe refractory eosinophilic asthma.[1]

Patients were randomised in a 1:1:1:1 ratio to receive one of three doses of intravenous (IV) mepolizumab (75mg, 250mg or 750mg)* or placebo,** every 4 weeks.[1]

*Unlicensed doses/route of administration
**When both treatments were added to high dose ICS and additional maintenance treatment(s)

Key efficacy findings

Treatment with mepolizumab provided:

Significant reductions in the rate of clinically significant exacerbations (primary endpoint) vs. placebo:[1]

  • 48% reduction with mepolizumab 75mg vs. placebo (p<0.0001; 1.24 vs. 2.4 annual event rates respectively)
  • 39% reduction with mepolizumab 250mg vs. placebo (p=0.0005; 1.46 vs. 2.4 annual event rates respectively)
  • 52% reduction with mepolizumab 750mg vs. placebo (p<0.0001; 1.15 vs. 2.4 annual event rates respectively)

Reductions in the rate of exacerbations requiring hospitalisation or emergency department (ED) admissions/visits vs. placebo (secondary endpoint):[1]

  • 60% reduction with mepolizumab 75mg vs. placebo (0.17 vs. 0.43 annual event rates, respectively)
  • 42% reduction with mepolizumab 250mg vs. placebo (0.25 vs. 0.43 annual event rates, respectively)
  • 48% reduction with mepolizumab 750mg vs. placebo (0.22 vs. 0.43 annual event rates, respectively)

Defined as episodes of acute asthma exacerbation requiring treatment with OCS, and/or hospitalisation and/or visit to an ED

Cumulative number of clinically significant exacerbations over 52 weeks[1]

Adapted from Pavord P et al. Lancet 2012; 380:651–659.

Key safety findings

  • Incidence of serious adverse events (AEs) was similar across treatment groups[1]
  • The most frequently reported AEs were headache and nasopharyngitis[1]
  • The most frequent drug-related AE was injection site reaction[1]

References:

  1. Pavord P et al. Lancet 2012; 380:651–659.
  2. Nucala Summary of Product Characteristics
  3. Ortega H et al. N Engl J Med 2014; 371:1198–1207.
  4. Bel E et al. N Engl J Med 2014; 371:1189–1197.

MENSA investigated the efficacy and safety of Nucala in patients with severe refractory eosinophilic asthma[1]

Population

576 patients aged 12–82 years* with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled corticosteroids.[1]

Study design

MENSA (MEpolizumab as adjuNctive therapy in patients with Severe Asthma) was a randomised, multicentre, double-blind, double-dummy, placebo-controlled, Phase III clinical trial that investigated the efficacy and safety of mepolizumab.[1]

Patients were randomised to receive Nucala 100mg subcutaneous (SC), mepolizumab 75 mg IV or placebo in a 1:1:1 ratio added to high dose ICS and additional maintenance treatment(s).[3] Only the data from the Nucala 100 mg SC vs. placebo comparison are reported here.[1]

Inclusion criteria

All 576 patients met entry criteria informed from outcomes from DREAM, a dose ranging study:[1]

  • Regular treatment with high-dose ICS and at least 3 months of treatment with additional controller(s), with or without OCS, ≥2 exacerbations in the prior 12 months
  • Blood eosinophil levels of ≥150 cells/μL at initiation of treatment or ≥300 cells/μL in the prior 12 months[1]
  • All enrolled patients were also required to have one of:[1]

    FEV1 reversibility of more than 12%
    Positive results on methacholine or mannitol challenge at visit 1 or 2 or during the previous year
    FEV1 variability (≥20%) between two clinic visits in the past 12 months

Primary endpoint

The frequency of clinically significant exacerbations in patients with severe eosinophilic asthma at Week 32.[1]

Secondary endpoints

These included:[1]

Rate of exacerbations requiring hospitalisation/ED visits
Mean change from baseline
  • in St. George's Respiratory Questionnaire score
  • in pre-bronchodilator FEV1 at Week 32

ED, Emergency department; FEV1, Forced expiratory volume after 1 second; ICS, Inhaled corticosteroids; IV, intravenous; OCS, Oral corticosteroids; SC, Sub-cutaneous
*Nucala is indicated as add-on treatment for SC use in adult patients with severe refractory eosinophilic asthma only
Unlicensed dose/route of administration.

Reference:

  1. Ortega HG et al. N Engl J Med 2014; 371:1198–1207.

SIRIUS investigated the corticosteroid-sparing effect of Nucala as an add-on therapy in patients with severe refractory eosinophilic asthma[1]

Population

135 patients aged 16–74* years with severe refractory eosinophilic asthma.[1]

Study design

SIRIUS (SteroId ReductIon with MepolizUmab Study) was a 32-week, randomised, multicentre, double-blind, placebo-controlled, parallel-group, Phase III clinical trial that investigated the effect of Nucala in reducing the use of maintenance OCS while maintaining asthma control.[1]

Patients received mepolizumab 100 mg or placebo administered subcutaneously every 4 weeks for 20 weeks.[1]

Inclusion criteria

These included:[1]

  • Regular treatment with high dose ICS and an additional maintenance treatment(s)
  • Maintenance treatment with OCS for at least 6 months (5–35mg/day prednisone or equivalent)
  • Blood eosinophil level of ≥150 cells/μL at the start of the study or ≥300 cells/μL in the prior 12 months

Primary endpoint

The percent reduction in daily OCS dose (Weeks 20–24) whilst maintaining asthma control in patients treated with Nucala, vs. those treated with placebo.[1]

Secondary endpoints

During Weeks 20–24 while maintaining asthma control were:[1]

  • Proportion of subjects who achieved a reduction of 50% in their daily OCS dose compared with baseline dose
  • Proportion of subjects who achieved a reduction of OCS dose to 5.0mg/day or less
  • proportion of subjects who achieved a total cessation of OCS dose
  • median percentage reduction from baseline in daily OCS dose

ICS, Inhaled corticosteroids; IV, intravenous; OCS, Oral corticosteroids.
*Nucala is indicated as add-on treatment for SC use in adult patients with severe refractory eosinophilic asthma only.
**During the optimisation phase (3–8 weeks before study start), OCS dose was reduced weekly until there was an exacerbation in asthma symptoms or an increase of at least 0.5 points from Visit 1 on the asthma control questionnaire (ACQ)-5. The median OCS dose following optimisation was 10.0mg for patients receiving Nucala and 12.5mg for placebo recipients.[1]
During the reduction phase (Weeks 4–20), OCS dose was reduced according to a pre-specified schedule by 1.25mg to 10mg per day every 4 weeks on the basis of asthma control and symptoms of adrenal insufficiency.[1]

Reference:

  1. Bel E et al. N Engl J Med 2014; 371:1189–1197

COSMOS was a 52-week, open-label extension study (of MENSA or SIRIUS) that investigated the long-term safety and efficacy of Nucala in severe eosinophilic asthma[1]

Population

651 patients with severe eosinophilic asthma who had been enrolled in the 32-week MENSA trial or the 24-week SIRIUS trial.[1-3]

  • 414 (64%) had previously received mepolizumab intravenously* or subcutaneously
  • 237 (36%) had previously received placebo

Study design

All patients received open-label Nucala – administered every four weeks – and continued to receive standard of care, including controller therapy, throughout.[1]

Adapted from Lugogo N et al. 2016.

Primary endpoint

The long-term safety profile of mepolizumab in patients with severe eosinophilic asthma.[1]

Secondary endpoints

These included:[1]

  • blood eosinophil count
  • annualised rate of exacerbations
  • 5-item Asthma Control Questionnaire (ACQ-5) scores and FEV1

Durability of response, defined as rate of exacerbations and OCS dose, was also assessed in post-hoc analyses.[1]

*Unlicensed dose/route of administration[2]

References:

  1. Lugogo N et al. Clin Ther 2016; 38:2058–2070.
  2. Ortega HG et al. N Engl J Med 2014; 371:1198–1207.
  3. Bel E et al. N Engl J Med 2014; 371:1189–1197

MUSCA investigated the effect of Nucala as an add-on therapy on health-related quality of life in patients with severe eosinophilic asthma[1]

Population

276 patients aged 12 years* or older with severe eosinophilic asthma.[1]

Study design

MUSCA was a 24-week phase 3b, placebo-controlled, double-blind, parallel-group, multicentre study that investigated the effect of Nucala on disease-specific health-related quality of life (HRQOL).[1]

Patients were randomly assigned (1:1) to receive a subcutaneous injection of either mepolizumab 100 mg or placebo, plus standard of care, every 4 weeks for 24 weeks (final dose given at week 20).[1]

Adapted from Chupp GL et al. 2017.

Inclusion criteria

  • A history of at least two exacerbations requiring treatment in the previous 12 months before screening despite regular use of high-dose inhaled corticosteroids[1]
  • Additional controller medication(s) for at least 3 months before screening[1]
  • Pre-bronchodilator FEV1 < 80% predicted in those aged ≥18 years, or less than 90% predicted in those aged 12–17 years[1]

Primary endpoint

Mean change from baseline in SGRQ total score at Week 24.[1]

Secondary endpoints

These included:[1]

  • Mean change from baseline in pre-bronchodilator FEV1
  • Proportion of SGRQ total score responders (patients achieving a ≥4-point reduction from baseline in SGRQ score)
  • Mean change from baseline in ACQ-5 score

ACQ, Asthma Control Questionnaire; FEV1, Forced expiratory volume after 1 second, SGRQ, St George’s Respiratory Questionnaire.
*Nucala is indicated as add-on treatment for SC use in adult patients with severe refractory eosinophilic asthma only.

Reference:

  1. Chupp GL et al. Lancet Respir Med 2017; 5:390–400.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Adverse events should be reported to the Health Products Regulatory Authority (HPRA) using an Adverse Reaction Report Form obtained either from the HPRA or electronically via the website at www.hpra.ie. Adverse reactions can also be reported to the HPRA by calling: (01) 6764971. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.

NUCALA is a registered trademark of the GlaxoSmithKline Group of Companies.

IE/NLA/0012/18 Date of prep: March 2018