The FDA’s Pulmonary Allergy Drugs Advisory Committee voted voted 16-3
against recommending GlaxoSmithKline’s mepolizumab (Nucala) as an add-on treatment to inhaled corticosteroid-based maintenance treatments to reduce flare-ups in patients with chronic obstructive pulmonary disease
The indication would have been a novel one, guided by patient’s blood eosinophil counts. Nucala, a biologic, is already approved for severe asthma
. Mepolizumab, a monoclonal antibody, targets interleukin-5 (IL-5), a type-1 cytokine that plays a key role in the triggering eosinophilic airway inflammation.
According to a 100-page FDA briefing document
released this week, the committee had many questions about the possibility of approving mepolizumab for COPD, an incurable, progressive disease. Those questions included ones regarding efficacy (1 of 2 pivotal trials failed to meet endpoints); the company did not include variables about patient history, which could have affected results; and there is a lack of consensus about the definition of eosinophil COPD.
The FDA noted that “investigations of a subset of COPD patients who experience airway inflammation with a measurable eosinophilic component led to efforts to characterize 'eosinophilic COPD' as a distinct, clinically meaningful phenotype. Despite research, uncertainty still exists regarding accurate defining criteria of the phenotype, the importance of sputum eosinophils versus peripheral blood eosinophils (PB-Eos) as biomarkers, and the clinical impact of the eosinophilic COPD phenotype in patient care and drug development.”
The committee also noted that GlaxoSmithKline was not able to replicate efficacy when mepolizumab was given at 100 mg and also at 300 mg. The committee also raised concerns about the fact that the company did not collect data on patient asthma history nor use of chronic maintenance oral corticosteroids for COPD, which could have affected the results.
“In particular, any observed benefit of mepolizumab on exacerbations could be driven primarily or entirely by an effect in patients with concomitant asthma, given that asthma exacerbations and COPD exacerbations are not well differentiated clinically. Asthma-related adverse events appear in the safety database, suggesting subjects with active asthma were present in the trials,” the document said.
Other IL-5 biologics for severe asthma
include reslizumab (Cinqair) and benralizumab (Fasenra), but so far, expanding these drugs to COPD is proving to be tricky. In May, AstraZeneca and MedImmune reported negative phase 3 trial results for benralizumab for COPD, reported MDMag, a sister site of The American Journal of Managed Care®
In its briefing documents
for the committee, GlaxoSmithKline said there is a high, unmet need to provide medications for the subgroup of patients with COPD who continue to have exacerbations while using triple therapy, and that they have a 26% greater risk of death.
In a statement after the vote, GlaxoSmithKline noted the committee voted 17-2 that there was adequate evidence of the safety of mepolizumab in this population of COPD patients. It also said "the committee suggested further data to characterise the patient population that would be most likely to benefit from this targeted biologic therapy."
“Having participated in today’s advisory committee meeting and heard the recommendation we will continue to work with the FDA to address outstanding questions," said Dave Allen, senior vice president, Respiratory Therapy Area, Research and Development. "We remain confident our data supports mepolizumab as a targeted treatment for patients continuing to experience COPD exacerbations guided by blood eosinophil count.”
The FDA is not required to take the advice of its advisory committees, but usually does.