GlaxoSmithKline to seek approval of mepolizumab this year for COPD

GlaxoSmithKline said Tuesday that it plans to file marketing applications seeking approval of mepolizumab in chronic obstructive pulmonary disease (COPD) later this year, despite mixed late-stage study results. The monoclonal antibody, which targets the signalling protein IL-5, is currently authorised in the US, Europe, Japan and a number of other markets, under the name Nucala, for the treatment of certain patients with asthma.

According to GlaxoSmithKline, the decision to seek approval of mepolizumab in COPD follows discussions with external experts, and coincides with the publication of full results from Phase III studies of the drug in this indication in the NEJM, as well as presentation at the European Respiratory Society (ERS) congress.

The METREX and METREO studies were designed to evaluate the efficacy and safety of mepolizumab as add-on therapy in the reduction of moderate to severe COPD exacerbations in patients at high risk of exacerbations and to identify those subjects most likely to respond to treatment using blood eosinophils as a biomarker. The METREX trial investigated mepolizumab at a dose of 100 mg versus placebo, while the METREO study evaluated the therapy at doses of 100 mg and 300 mg compared to placebo.

Results showed that in the METREX study, for the primary endpoint in patients receiving mepolizumab with higher eosinophils, there was a significant reduction of 18 percent in the frequency of moderate and severe exacerbations versus placebo. The company said that data also indicated that patients with blood eosinophil counts of less than 150 cells/mL at the start of the trial were not found to benefit from mepolizumab.

Meanwhile, in the METREO study, for the main goal in patients receiving the two doses of GlaxoSmithKline's drug with higher eosinophils, reductions in the frequency of moderate and severe exacerbations were 20 percent and 14 percent, respectively, which were not significant compared to placebo. The drugmaker added that there was no evidence of greater treatment effect in patients treated with the 300 mg dose of mepolizumab.

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GlaxoSmithKline noted that a pre-specified meta-analysis of both studies showed that rates of exacerbation reduction increased as blood eosinophil counts increased, which the company said points to the relevance of blood eosinophils as a biomarker to help identify COPD patients most likely to respond to treatment with mepolizumab. Steve Yancey, medicine development lead for mepolizumab, commented "we believe the data…demonstrate the benefits of a personalised medicine approach in the treatment of COPD with mepolizumab, using blood eosinophils as a biomarker."

Further results showed that regarding secondary endpoints, there was a significant increase in the time to first moderate and severe exacerbation in the METREX study, with numerical, but not significant, increase in time to first exacerbation in the METREO trial. GlaxoSmithKline added that there were no significant differences between mepolizumab and placebo in either study on the remaining secondary endpoints, including annual rate of exacerbations requiring emergency department visit and/or hospitalisation, St George’s Respiratory Questionnaire score and COPD assessment test score.

For related analysis, see Physician Views Poll Results: Treatment costs and role of biomarkers will shape market for biologic asthma therapies, say prescribers.

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