Regulators in the USA are being asked to consider revoking approval in children under 18 for certain asthma drugs including GlaxoSmithKline’s Advair and Schering-Plough’s Foradil.
Ahead of an advisory committee meeting this week, staffers at the US Food and Drug Administration have issued a draft review of a meta-analysis of four drugs that contain a long-acting beta agonist – GSK’s Advair/Seretide (salmeterol, fluticasone) and Serevent (salmeterol), S-P’s Foradil (formoterol) and AstraZeneca’s Symbicort (formoterol, budesonide). The study explored possible associations of the four LABAs currently marketed in the USA with asthma-related hospitalisation and intubation, plus asthma-related death. Serevent and Foradil contain LABAs only, while Advair and Symbicort combine them with an inhaled steroid.
The analysis, which compared patients taking a LABA to those using steroids alone to control their asthma, used data from 110 trials and almost 61,000 patients. The majority, just shy of 44,000, were taking Serevent, while Advair trials accounted for over 13,000 subjects.
The findings showed that Foradil, Symbicort and Serevent had a higher rate of overall risk of complications versus steroids but the difference was only statistically significant in the case of the latter. No increased risk was seen with Advair.
Still, the FDA staffers unanimously recommended that Serevent and Foradil, ie the two LABA-only drugs, should no longer be approved for treating asthma. Furthermore, they argue that none of the drugs should be used in children under 18, claiming that they are at greater risk of developing respiratory complications.
Badrul Chowdhury, director of the FDA’s Division of Pulmonary and Allergy Drug Products,, acknowledged a “serious and significant safety risk” but added the asthma-related deaths in the analysis were “numerically small” and the benefits were “not trivial.” He wrote that “removal of inhaled LABAs from the market as a treatment for asthma is a way of managing the risk of these drugs, but would be an extreme approach that could be problematic”.
GSK said the data confirmed that Serevent is effective and showed no increased risk of serious asthma-related outcomes when it was used appropriately with an inhaled corticosteroid. However the firm noted that it has asked the FDA to revise the product label to direct that Serevent be used only with an ICS when treating asthma, noting that such advice is already listed in the European label of the drug.
