GSK Receives CRL for Mepolizumab's COPD Add-On Therapy Application

GlaxoSmithKline (GSK) has received a complete response letter (CRL) from the US Food and Drug Administration (FDA) in reply to the pharmaceutical company’s application for mepolizumab as an add-on therapy for patients with chronic obstructive pulmonary disease (COPD).

GSK’s application for mepolizumab vied for it to serve as an add-on therapy to inhaled corticosteroid-based maintenance treatment in patients with COPD, as guided by patient blood eosinophil counts.

According to GSK, the CRL for mepolizumab stated that more clinical data is required in COPD to support an FDA approval. The company stated intentions to work closely with the FDA to determine the next steps for mepolizumab, to resume its bid for a supplementary biologics license application (sBLA) approval.

Clinical trial results from the METREX and METRO studies were submitted as part of the new drug application for mepolizumab in COPD. In findings published in the New England Journal of Medicine, patients with COPD treated with add-on 100mg mepolizumab showed a consistent 18% to 20% reduction in the annual rate of moderate and severe exacerbations. The 18% benefit was seen in the METREX study and was statistically significant versus placebo (P = .036); however, significance was not met in the METREO trail (P = .068).

In addition, there was a statistically significant improvement the time to first moderate and severe exacerbation in the METREX trial. This endpoint was not significantly improved in METREO. Other secondary endpoints were not improved with add-on mepolizumab compared with placebo.

“For people living with COPD, a sudden worsening of their symptoms, known as an exacerbation, causes them to struggle to breathe despite receiving the available guideline recommended treatment," lead author Ian Pavord, MD, DM, Nuffield Department of Medicine, University of Oxford, said in the findings were published. "For these patients, there are currently no other treatment options. When considering the challenges these patients face, the exacerbation reduction shown in the METREX and METREO studies is a clinically important outcome.”

The first-in-class interleukin-5-targeting monoclonal antibody mepolizumab was first approved in 2015 for the treatment of severe eosinophilic asthma. It has been assessed in more than 3000 patients across 16 clinical trials pertaining to various eosinophilic indications, according to GSK, and is currently being investigated for severe hypereosinophilic syndrome and nasal polyposis.

At the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA, this May, results from the phase 3 open-label COLUMBA study showed patients with severe eosinophilic asthma had a 61% mean decrease in annual exacerbation rates during an average of 3.5 treatment years. Events dropped from 1.74 events per year at enrollment to 0.68 (95% CI, 0.60-0.78). Annual exacerbation rates in patients immediately fell to within that range, and was maintained over time (0.71 in year 1; 0.82 in year 2; 0.71 in year 3).

When the results were released at ATS, Dave Allen, head of the Respiratory Therapy Area of Research and Development for GSK, said the study findings were indicative of mepolizumab’s long-term benefit to this patient population.

“The findings show the sustained exacerbation reduction and asthma control delivered by this medicine over a substantial length of time, with no new safety findings,” Allen said.