- The Food and Drug Administration has declined to approve GlaxoSmithKline's lung drug Nucala for chronic obstructive pulmonary disease, issuing the British drugmaker a Complete Response Letter on Friday.
- While not a surprise after a negative advisory panel vote last month, the rejection crimps GSK's plans to expand the addressable market for the medicine that targets IL-5. Respiratory diseases are a key focus for GSK, the maker of the blockbuster inhaler Advair.
- In its letter, the FDA asked for more clinical data to support an approval in COPD, the drugmaker said. Briefing documents prepared by FDA staff for July's advisory committee meeting questioned the potential of targeting the IL-5 pathway, as well as data from one of the two studies supporting GSK's application.
Unlike standard COPD treatments which rely on inhaled corticosteroids and bronchodilators, Nucala (mepolizumab) is a biologic drug. If approved, it would have become the first biologic therapy for COPD.
But, unfortunately for GSK, the FDA wasn't convinced by an application that included results from a late-stage study that missed its primary goal.
GSK had submitted its pitch to the agency last fall, seeking an approval for Nucala's use as an add-on therapy to maintenance treatment for the reduction of exacerbations in COPD patients. Importantly, the drugmaker developed Nucala with a focus on its effect on blood counts of eosinophils — a marker of inflammation.
In a meeting last month, a committee of independent advisors voted 3 to 16 against finding Nucala's risk-benefit profile supportive of approval in COPD. Additionally, the experts judged there to be insufficient data to characterize the patient population who would be most likely to benefit from a IL-5 targeting biologic.
It was an opinion shared by FDA staff, who raised concerns in briefing documents for the meeting.
"The lack of consensus surrounding the definition of the eosinophilic COPD phenotype creates challenges in defining the group of patients that could derive benefit from mepolizumab," FDA staff wrote.
AstraZeneca, GSK's rival in respiratory disease, has faced similar challenges. The competing British pharma currently doesn't plan to submit its new lung drug Fasenra (benralizumab) for COPD after results from two trials showed the treatment failed to reduce disease flare-ups. Fasenra also targets the IL-5 pathway.
The FDA raised the outcome of those studies in its preparation to review Nucala, indicating the trial misses raised questions "regarding the potential of the target."
Currently, Nucala carries approvals for severe eosinophilic asthma and a rare autoimmune condition marked by airway inflammation. It's one of a handful of new drugs that are particularly important to GSK and its competitiveness amid slumping sales of Advair (fluticasone furoate/salmeterol).
GSK does have an advantage over AstraZeneca, however, in that it already won approval for a three-in-one inhaler for COPD. AstraZeneca is testing a triple inhaler of its own, and expects to file for a U.S. OK sometime later this year.