FDA rejects GSK’s Nucala for COPD

There was bad if not unexpected news for GlaxoSmithKline late Friday, after the FDA refused to extend the indications of its asthma drug Nucala to include chronic obstructive pulmonary disorder (COPD).

The US regulatory agency issued a complete response letter (CRL) to GSK for Nucala (mepolizumab) as an add-on to inhaled corticosteroid-based maintenance treatment to reduce exacerbations – a sudden worsening of symptoms – in COPD patients with elevated eosinophil level.

The decision hasn’t come out of left field, as in July an FDA advisory committee voted 16 to three against approving the drug in this indication, following the advice of the agency reviewers who suggested that GSK had failed to provide sufficient evidence that Nucala was effective in preventing COPD exacerbations.

“GSK will work closely with the FDA to determine the appropriate next steps for the supplementary biologics licence application (sBLA)” in COPD, said the drugmaker in a statement.

Nucala was the first interleukin-5 (IL-5) inhibitor to be approved for marketing, getting a green light from the FDA as a treatment for severe asthma associated with elevated eosinophil levels back in 2015.

Since then it has grown fairly slowly, making £245m ($317m) in the first six months of the year, but is now facing competition from other IL-5 inhibitors including AstraZeneca’s Fasenra (benralizumab) and Teva’s Cinqair/Cinqaero (reslizumab). Another potentially strong challenge could come from AZ and Amgen’s tezepelumab, which has just been awarded a breakthrough designation from the FDA for severe asthma.

Approval in COPD would give GSK a much larger eligible patient population for Nucala and keep it ahead of its rivals, but clinical data for the drug in this indication has been mixed.

In the METREX trial reported last year Nucala hit its objective of reducing moderate to severe exacerbations, cutting them by 18% compared to placebo, which scraped over the statistical significance threshold. The drug didn’t meet that efficacy target in a second study called METREO, however, although GSK said an analysis of the two studies in combination indicated the drug was effective in patients with higher eosinophil levels.

The FDA wasn’t comfortable with that idea, however, suggesting there is a lack of consensus among clinicians as to the definition of eosinophilic COPD – and whether it is actually a discrete subcategory of the disease. During the panel meeting, questions were also raised about a lack of data on patient history and specifically whether they had used chronic oral steroids for COPD, which could have skewed the results.

Meanwhile, Nucala isn’t the first drug in the IL-5 inhibitor class to run into trouble in COPD. In May, AZ’s Fasenra failed a phase III trial in this indication as it was unable to show a benefit compared to placebo reducing exacerbations.