FDA is seeking additional efficacy data on GlaxoSmithKline's Flovent Diskus and Advair Diskus for chronic obstructive pulmonary disease before approving the products for the supplementary indication.

The agency issued an "approvable" letter on March 5, asking GSK for more efficacy data on COPD exacerbations and clinical outcomes.

FDA also requested additional safety data on the long-term use of Flovent (fluticasone 250 mcg or 500 mcg) and Advair (fluticasone 250 mcg or 500 mcg/salmeterol 50 mcg) in the COPD patient population.

GSK has acknowledged receipt of the "approvable" letter and plans to meet with FDA to work on ways to meet the agency's request.

GSK is seeking an indication of long-term, twice-daily maintenance treatment of COPD (including emphysema and chronic bronchitis) for Flovent, Advair and Serevent Diskus . FDA approved the Serevent application March 22. Supplemental NDAs for all three inhalation powder products were filed in May 2000.

FDA's Pulmonary-Allergy Drugs Advisory Committee reviewed Flovent and Advair for long-term treatment of COPD Jan. 17 (¹ [A#00640030007], p. 10).

The committee recommended FDA approve both products for the narrowed indication of chronic obstructive bronchitis rather than COPD, eliminating emphysema from the indication.

Committee members also suggested removing the "long-term maintenance" portion from the proposed indication, citing concerns with the length of follow-up in clinical trials.

Members questioned the efficacy of fluticasone, but not salmeterol, for maintenance therapy of COPD. The committee voted that Flovent at the lower 250 mcg dose did not demonstrate efficacy, but concurred that efficacy had been shown for Advair at both doses.

The committee did not review Serevent's proposed COPD indication because FDA did not request committee input on the application.

FDA approved Serevent (salmeterol 50 mcg) "for the long-term, twice-daily (morning and evening) administration in the maintenance treatment of bronchospasm associated with COPD (including emphysema and chronic bronchitis)."

The approval was based on data from two 24-week Phase III trials in 366 patients with chronic bronchitis and airflow limitation, with or without emphysema.

Serevent patients showed an average of 20% (216 mL) improvement in FEV1 (forced expiratory volume in one second) two hours post-dose, compared to an average of 5% improvement (43 mL) in the placebo group.

Revised labeling states that "the mean daily need for additional beta 2-agonists for patients using salmeterol inhalation powder was approximately 4 inhalations/day." Twenty-four percent of patients using salmeterol in the trials averaged six or more inhalations of albuterol per day over the course of 24 weeks.

Adverse events include headache (14%), musculoskeletal pain (12%), throat irritation (7%), cough (5%), viral respiratory infection (5%) and hypertension (4%).

Serevent was approved for treatment of asthma and prevention of exercise-induced bronchospasm in 1997; Advair and Flovent were approved for asthma in 2000 and 1996, respectively.

FDA's approval letter includes a request that GSK revise the packaging for Serevent.

GSK is being asked to "increase the prominence of the storage statement on your carton and container labels...since the performance of the drug product is dependent upon temperature and humidity conditions."

Revised labeling reminds patients to "always keep the diskus in a dry place" and to "discard 6 weeks after removal from the moisture-protective foil overwrap pouch or after all blisters have been used...whichever comes first."

The agency also requested that GSK increase the prominence of the established name on the carton and container labels.

GSK Flovent/Advair Diskus Needs More COPD Data; Serevent Cleared For COPD

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