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Nucala clinical trial data

Learn about the Phase III clinical trial data for Nucala – a targeted anti-IL-5 add-on therapy for adults, adolescents and children ≥ 6 years with severe refractory eosinophilic asthma. 1

In the MENSA study, Nucala reduced the rate of clinically significant exacerbations by 53% vs. placebo (primary endpoint, 95% CI 36-65%), when both were added to high dose ICS and an additional maintenance treatment(s). Improved measures of quality of life and lung function (secondary endpoints) were also observed however statistical significance cannot be inferred due to the hierarchical ‘gate-keeping’ approach used.

In the SIRIUS study, Nucala reduced patients’ daily OCS dose, while maintaining asthma control vs. placebo (primary endpoint).

Exacerbation data

Nucala significantly reduced exacerbations by 53% (MENSA primary endpoint)

Nucala reduced clinically significant exacerbations vs. placebo when both were added to high dose ICS and an additional maintenance treatment(s). 2

Reduction in exacerbation frequency vs. placebo at Week 32 (primary endpoint) 2

  • At the start of the study, the baseline rate of exacerbations was similar for both treatment arms (placebo: 3.6/year; Nucala: 3.8/year) 2
  • Clinically significant exacerbations of asthma were defined as the worsening of asthma that required use of systemic corticosteroids for at least three days or required hospitalisation and/or emergency department (ED) visits 2

For more information on the MENSA study design

 

Nucala also significantly reduced exacerbations resulting in hospitalisation and/or emergency department (ED) visits (MENSA secondary endpoint)

Nucala also significantly reduced exacerbations resulting in hospitalisations and/or ED visits vs. placebo when both were added to high dose ICS and an additional maintenance treatment(s) by 61% (Nucala: 0.08/year, placebo: 0.2/year; 95% CI 17-82% p=0.02).* 2

Nucala reduced blood eosinophils by 84% at Week 32

Nucala added to high dose ICS and an additional maintenance treatment(s) reduced blood eosinophil levels by 84% compared with placebo added to high dose ICS and an additional maintenance treatment(s) at Week 32. 1

Nucala treatment led to a reduction in geometric mean count from 290 cells/μL (0.29 x 109 cells/L) at baseline to 40 cells/μL (0.04 x 109 cells/L) at Week 32. 1

For more information on the MENSA study design

Quality of life data

Nucala improved health-related quality of life (MENSA secondary endpoint)

Nucala improved health-related quality of life (measured using SGRQ) vs. placebo when both were added to high dose ICS and an additional maintenance treatment(s) by 7.0 units (95% CI -10.2 to -3.8). 2

Improvement in SGRQ total score from baseline at Week 32 (MENSA secondary endpoint) 2

Statistical significance cannot be inferred due to the hierarchical ‘gatekeeping’ approach used. The p-values provided are unadjusted for multiple comparisons.

  • At the start of the study, baseline SGRQ total scores were similar for both treatment arms (placebo: 46.9 units; Nucala: 47.9 units). 2
  • The St. George’s Respiratory Questionnaire (SGRQ) is a validated disease-specific health status assessment for use in asthma and COPD and a difference of ≥4 units is considered clinically meaningful. 3

For further information on the MENSA study design.

Lung function data

Nucala improved lung function (MENSA secondary endpoint)

Nucala improved lung function (as measured by pre-bronchodilator FEV1) vs. placebo when both were added to high dose ICS and an additional maintenance treatment(s) by 98mL (95% CI 11-184ml). 2

Improvement in lung function from baseline at Week 32 (MENSA secondary endpoint) 2

Statistical significance cannot be inferred due to the hierarchical ‘gatekeeping’ approach used. The p-values provided are unadjusted for multiple comparisons.

  • At the start of the study, baseline values were similar for both treatment arms (placebo: 1860mL, Nucala: 1730mL). 2

For further information on the MENSA study design

Oral corticosteroid sparing data

Nucala reduced patients’ daily OCS dose, while maintaining symptom control (SIRIUS primary endpoint)

The odds of achieving a reduction in OCS dose while maintaining symptom control were 2.39 times higher in patients receiving Nucala (n=69) vs. placebo* (n=66; 95% CI 1.25-4.56; p=0.008) 4

  • 54% (37/69) of Nucala patients achieved at least a 50% reduction in the daily OCS dose compared with 33% (22/66) of patients receiving placebo* (secondary endpoint, odds ratio 2.26 (95% CI 1.10-4.65), p=0.03) 4
  • 54% (37/69) of Nucala patients achieved a reduction in the daily OCS dose to ≤5mg compared with 32% (21/66) of subjects receiving placebo* (secondary endpoint, odds ratio 2.45 (95% CI 1.12-5.37), p=0.02) 4
  • The median percentage reduction in daily OCS dose was 50% (95% CI 20.0 to 75.0%) in the Nucala group, compared with 0% (95% CI -20.0 to 33.3%) in the placebo group* (secondary endpoint, p=0.007) 4
  • In the Nucala group, 14% (10/69) of patients achieved a total cessation of OCS dose compared with 8% (5/66) in the placebo group* (secondary endpoint, odds ratio 1.67 (95% CI 0.49-5.75) p=ns) 4

*when both were added to high dose ICS and an additional maintenance treatment(s)

  • At the start of the study the baseline median daily OCS dose (optimised dose) was similar between treatment groups (placebo: 12.5mg; Nucala: 10.0mg). 4

For further information on the SIRIUS study design

Safety data from the Nucala clinical trial programme

Safety profile of Nucala

A total of 915 patients with severe refractory eosinophilic asthma have received either a subcutaneous (SC) or intravenous (IV) dose of Nucala during clinical studies of 24 to 52 weeks duration. Nucala is licensed for SC use only. 1

Adverse reactions from the MENSA and SIRIUS placebo-controlled studies in patients receiving Nucala 100mg SC (n=263) as well as spontaneous post-marketing reporting 1

The frequency of adverse reactions is defined using the following convention: very common (≥1/10), common (≥1/100 to <1/10) and rare (≥1/10 000 to <1/1 000).

*Systemic reactions including hypersensitivity have been reported at an incidence comparable to that of placebo. 1
** From spontaneous post-marketing reporting
*** 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 mepolizumab 100 mg subcutaneously.
 1

In the MENSA and SIRIUS studies, the incidence of adverse events and serious adverse events with Nucala were found to be similar to placebo when both were added to high dose ICS and an additional maintenance treatment(s), 124with the exception of injection site reactions, which were more frequent with Nucala (8% [21/263] for Nucala, 3% [8/257] for placebo). 1

Incidence of adverse events and serious adverse events in the MENSA and SIRIUS studies 24

  • Injection site reactions occurred mainly at the start of treatment and within the first three injections with fewer reports on subsequent injections. 1

For more information on the MENSA and SIRIUS studies.

Special warnings and precautions for use  1

Nucala should not be used to treat acute asthma exacerbations.

Asthma-related adverse events or exacerbations may occur during treatment. Patients should be instructed to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment.

Abrupt discontinuation of corticosteroids after initiation of Nucala therapy is not recommended. Reduction in corticosteroid doses, if required, should be gradual and performed under the supervision of a physician.

Hypersensitivity and administration-related reactions

Acute and delayed systemic reactions, including hypersensitivity reactions (e.g. urticaria, angioedema, rash, bronchospasm, hypotension), have occurred following administration of Nucala. These reactions generally occur within hours of administration, but in some instances have a delayed onset (i.e., typically within several days). These reactions may occur for the first time after a long duration of treatment.

Parasitic infections

Eosinophils may be involved in the immunological response to some helminth infections. Patients with pre-existing helminth infections should be treated before starting therapy. If patients become infected whilst receiving treatment with Nucala and do not respond to anti-helminth treatment, temporary discontinuation of therapy should be considered.

References:

  1. Nucala SmPC.
  2. Ortega H, Liu MC, Pavord ID et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014; 371(13):1198-1207.
  3. Jones PW.St. George's Respiratory Questionnaire: MCID. COPD 2005; 2(1):75-79.
  4. Bel E, Wenzel SE, Thompson PJ et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014; 371(13):1189-1197.

Nucala is a trademark of the GSK group of companies