An FDA review panel is questioning the safety profile of umeclidinium/vilanterol (Anoro Ellipta), a once-daily treatment option for chronic obstructive pulmonary disease, after noting inconsistencies in data from clinical trials.
GlaxoSmithKline is seeking to market Anoro Ellipta as a once-daily bronchodilator for the long-term, maintenance of airflow obstruction in COPD patients, including chronic bronchitis and emphysema.
The drug combines 62.5 mcg of the long-acting antimuscarinic agent (umeclidinium) and 25 mcg of the long-acting beta-agonist (vilanterol). Although short-acting antimuscarinic agents and beta-agonists have been used in combination products, long-acting drugs have not previously been used together.
The safety of combination umeclidinium/vilanterol was studied in four six-month efficacy trials and one year-long, placebo-controlled safety study.
Although the number of cardiovascular-related events was “fairly low,” and the overall cardiovascular safety profile is “mostly unremarkable,” the panel has noted discrepancies in certain safety signals.
“Namely, a small imbalance in the primary efficacy trials was observed for nonfatal myocardial infarction that was not seen in the 12-month safety trial or in the larger integrated, exposure-adjusted COPD safety database,” the FDA reviewers said.
Also, patients were pulled out of different studies at varying rates due to abnormal EKG and Holter readings. However, withdrawal rates due to adverse events were similar across treatment arms.
In May, the FDA approved vilanterol in combination with the corticosteriod fluticasone furoate (Breo Ellipta, GlaxoSmithKline) to reduce exacerbations of COPD in patients with a history of exacerbations.
Umeclidinium is a novel agent not currently available as a monotherapy or in another combination product, but GSK currently has a marketing application under review for umeclidinium as a stand-alone drug.
Data from trials testing the efficacy of umeclidinium/vilanterol are promising. Results from two placebo-controlled trials show that after 169 days the combination drug improved mean trough FEV1 by 0.207 L/s and 0.171 L/s compared with -0.031 L/s and 0.004 L/s for placebo, respectively (P<0.001).
- Pulmonary Allergy Drugs Advisor Committee. FDA Briefing Document. NDA 203-975: umeclidinium and vilanterol inhalation powder for the long-term, once-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD). Sept. 10, 2013. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Pulmonary-AllergyDrugsAdvisoryCommittee/UCM367411.pdf