GSK's Nucala Comes Out Ahead in Comparison of Cinqair, Fasenra, Study Says

In an indirect treatment comparison (ITC) of 3 drugs for severe eosinophilic asthma, GlaxoSmithKline’s (GSK) mepolizumab, marketed as Nucala, reduced exacerbations by 34% to 45% compared with reslizumab or benralizumab. The results were published in The Journal of Allergy and Clinical Immunology.

Reslizumab is sold under the name Cinqair by Teva, and benralizumab is sold under the name Fasenra by AstraZeneca.

Eosinophilic asthma is a severe form of the condition that doesn’t respond well to inhaled corticosteroids, even at high doses. White blood cells called eosinophils become overactive, causing inflammation that blocks the airway with fluid and mucous. This can cause bronchial spasms. Unlike forms of asthma that are triggered by allergies or an environmental reaction, patients with this condition do not typically have a history of allergies.

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All 3 drugs are monoclonal antibodies targeting interleukin-5, a type-1 cytokine that plays a key role in the triggering eosinophilic airway inflammation.

The latest news about mepolizumab follows Friday’s announcement that the FDA wants more clinical data before it will consider it for chronic obstructive pulmonary disease (COPD). An FDA advisory committee voted against approving the drug for COPD in July.

The ITC used data from a Cochrane review and independent searches, totaling 11 studies. Eligible studies were randomized, controlled trials in patients 12 years or older.

Endpoints included the annualized rate of clinically significant exacerbations and a change from baseline in Asthma Control Questionnaire (ACQ) score and forced expiratory volume in 1 second (FEV₁). Patients were included if they had an ACQ ≥1.5; they were stratified by baseline blood eosinophil counts.

The study showed that all 3 drugs significantly reduced clinically significant exacerbations, and improved asthma control and lung function versus placebo.

In a statement, GSK said the comparisons were performed on “patient populations grouped by baseline blood eosinophil count, which is known to influence treatment effect, and matched according to baseline ACQ score to allow like-for-like comparisons between treatments.”

Mepolizumab 100 mg was compared with:

• Reslizumab 3 mg/kg for eosinophilic subgroup ≥400 cells/μL
• Benralizumab 30 mg for eosinophilic subgroups ≥150, ≥300, ≥400 cells/μL

Mepolizumab significantly reduced the rate of clinically significant exacerbations by 34% to 45% compared with benralizumab across all baseline blood eosinophil count thresholds, and by 45% compared with reslizumab in the ≥400 cells/µL subgroup.

Mepolizumab was associated with significant improvements in patient-reported asthma control, as assessed by ACQ score, compared with reslizumab and benralizumab in the ≥400 cells/µL subgroup and benralizumab in the ≥150 cells/µL and ≥300 cells/µL0 subgroups.

A significant improvement in lung function of 110 mL (as assessed by change from baseline in prebronchodilator FEV₁), was observed for benralizumab versus reslizumab in patients with baseline blood eosinophil counts ≥400 cells/µL.

However, when treatment comparisons used the intent-to-treat populations and did not take into account differences in baseline blood eosinophil count or ACQ score, there were no significant differences between the 3 treatments. Accounting for baseline characteristics improved the accuracy of the comparative efficacy of the treatments, the researchers said.

Significant reductions in exacerbations requiring emergency department visit/hospitalization were also seen with mepolizumab versus placebo across all baseline blood eosinophil thresholds, and with reslizumab versus placebo among patients with ≥2 historic exacerbations and GINA Step 4/5 therapy, but not with benralizumab versus placebo.

Differences between treatments did not reach statistical significance when compared indirectly. However, the authors said when baseline blood eosinophil count were accounted for that the results suggested mepolizumab was associated with significantly greater reductions in asthma exacerbations and significantly greater improvement in asthma control at all baseline blood eosinophil thresholds assessed, compared with reslizumab or benralizumab.

GSK funded the study and said it had a role in the design of the analysis, data collection, data analysis, and data interpretation, but said it had no restrictions on access to the data or statements made in the journal article and that it was the authors’ decision to submit for publication.