In documents released Monday ahead of an FDA advisory panel meeting on July 25, agency reviewers questioned whether data submitted by GlaxoSmithKline support the efficacy of Nucala (mepolizumab) for the treatment of patients with sudden worsening of chronic obstructive pulmonary disorder (COPD) guided by blood eosinophil counts. Specifically, FDA staff noted that the IL-5 antagonist failed to meet the statistical threshold for efficacy in one clinical study, while the drugmaker also failed to specify the patient group that would benefit from the treatment.
According to the documents, GlaxoSmithKline's submission of Nucala in COPD was supported by efficacy and safety data from two Phase III studies. The reviewers explained that one trial, dubbed METREX, included patients with a broader range of peripheral blood eosinophil counts, with the primary analysis focusing on the high eosinophil stratum. Meanwhile, the second study, named METREO, only enrolled subjects meeting the criteria for the high eosinophil stratum.
In data unveiled last year, GlaxoSmithKline noted that Nucala met the primary endpoint of a significant reduction in the frequency of moderate and severe exacerbations versus placebo in METREX. Meanwhile, in METREO, the drugmaker acknowledged that the reduction in the frequency of moderate and severe exacerbations compared to placebo did not reach significance.
FirstWord reports in this therapy area: KOL Insight COPD: Find out how KOLs expect the market to evolve, which pipeline treatments are most promising, and which clinical trials will shape treatment decisions. Learn more.
Moreover, the FDA staff cited some issues in trial design, including the potential enrolment of patients with a history of asthma given that GlaxoSmithKline did not collect data on asthma history. The reviewers explained that given the marginal statistical significance in the METREX study, the potential inclusion of patients with asthma is an important consideration.
GlaxoSmithKline submitted Nucala for approval in the US last November for the treatment of COPD in patients with an eosinophilic phenotype, based on findings from the METREX and METREO studies. The company said earlier this year that it is aiming to boost sales of its newer respiratory products in an effort to offset declining revenue due to expiry for Advair (fluticasone propionate/salmeterol).
Nucala is currently approved in the US as an add-on maintenance treatment for patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. For related analysis, read ViewPoints: GlaxoSmithKline faces uphill battle in bid to secure COPD approval for Nucala. See also ViewPoints: A limited opportunity for new biologics in COPD is getting smaller.
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