FDA Issues Not-Approvable Letter for Advair 500/50 in COPD

GlaxoSmithKline (GSK) received a not-approvable letter Aug. 7 from the FDA for the use of Advair Diskus 500/50 to reduce exacerbations and increase survival in patients with chronic obstructive pulmonary disease (COPD). The agency’s action follows a previous FDA advisory committee recommendation that, in part, supported the claim.

Although the lower-dosage form of the product, Advair 250/50 (fluticasone propionate/ salmeterol inhalation powder), is currently approved for the treatment of COPD associated with chronic bronchitis, physician labeling specifically recommends against the use of Advair 500/50 for that condition.

“We are very surprised and disappointed by this FDA decision, particularly given the outcome of the FDA advisory committee meeting earlier this year,” Katharine Knobil, GSK vice president of respiratory clinical development for COPD, said.

The agency’s Pulmonary-Allergy Drugs Advisory Committee voted unanimously that there was convincing evidence that Advair 500/50 provided a clinically meaningful decrease in the incidence of COPD exacerbations when used as a chronic treatment.

However, committee members expressed concern that the higher-dose Advair may be associated with an increased risk of pneumonia, according to the FDA. In addition, the committee said that clinical evidence did not demonstrate a survival benefit with the product.

In reaching its not-approvable decision, GSK said the agency questioned how Advair 500/50 compared with Advair 250/50, particularly relating to the exacerbation claim. Although Advair 250/50 is approved to treat COPD, it is not approved to reduce COPD exacerbations.

GSK will be meeting with FDA to discuss this … in more detail and determine next steps, including discussion of data GSK has recently generated on the reduction of exacerbations with the Advair 250/50 strength,” the company said.