FDA posts LABA briefing documents

FDA posted briefing documents ahead of the March 10-11 joint meeting of the Pulmonary-Allergy Drugs Advisory and Drug Safety and Risk Management committees to discuss clinical trial designs to evaluate serious asthma outcomes with marketed long-acting beta-2 adrenergic agonists (LABA) when added to corticosteroids compared to corticosteroids alone to treat asthma. FDA has proposed a composite safety endpoint of asthma-related hospitalizations, asthma-related intubations, and asthma-related deaths for trials in adults and adolescents, and an endpoint of asthma-related hospitalizations for children.

The panel will be asked whether the proposed endpoints are adequate; what alternative endpoints could be considered; and what would be an acceptable non-inferiority margin. FDA also will ask the panel to discuss the advantages and disadvantages of a "real world" study design where corticosteroid levels can be titrated compared with a study design where the corticosteroid dose remains fixed. Last month, FDA said it would require manufacturers to update the labels for LABAs to treat asthma, as well as conduct additional safety studies for the drugs and develop a REMS. The agency noted that clinical trials for LABAs showed an increased risk of severe worsening of asthma symptoms, leading to hospitalization and death in some patients (See BioCentury Extra, Thursday, Feb. 18, 2010). ...