GlaxoSmithKline: Proposed Asthma Drug Warnings Would Not Make Big Impact

An FDA advisory panel has stressed that GlaxoSmithKline’s asthma treatments Serevent and Advair, and Novartis’s Foradil, should carry new warnings emphasizing their potential risk to children. However, since all three drugs already carry black box warnings it is unlikely that a revised label will have much of an impact on the way these drugs are prescribed.

An FDA advisory committee has stated that GlaxoSmithKline’s Serevent (salmeterol) and Advair (salmeterol/fluticasone) should get new warning language in their labels about their potential risk for children. The agency plans to conduct a review of the drugs’ safety in children, which will also examine a similar treatment, Foradil (formoterol), made by Novartis and sold in the US by Schering-Plough.

Serevent belongs to a class known as long acting beta2-agonists (LABAs) while Advair is an ICS (inhaled corticosteroid)/LABA combination. Both drugs comprise of salmeterol and, as a result, carry a ‘black box’ label warning, the FDA’s strongest, saying that use of salmeterol may increase the risk of asthma-related death.

Safety concerns over salmeterol were raised when results from the 1996 SMART trial showed a possible increased mortality rate in certain subgroups of patients with asthma using Serevent. The rate of such deaths in studies was 0.1%, or 13 out of 12,176, for salmeterol patients, compared with 0.02%, or three out of 13,179, in those taking placebo. On reviewing these results, the FDA panel agreed that this may be a class effect and extended the warning to Novartis’s Foradil.

The panel has now stressed that the labels need to be revised with a more specific warning to children. They should also say that the drugs may increase the risk of asthma-related hospitalizations and that there should be more prominent language noting that the drugs are to be used in combination with other drugs designed to control acute asthma attacks, not alone.

However, guidelines for asthma treatment already state that LABA monotherapy should not be administered in any age group. According to Datamonitor research, very few US physicians prescribe LABA monotherapy and the most likely circumstance under which a LABA would be taken as monotherapy is through non-compliance with ICS therapy.

In addition, since all three drugs already carry a general warning, it is unlikely that an updated label emphasizing the risk of LABAs for children will have much of an impact on the way these drugs are prescribed. However, were the FDA to remove the pediatric indication altogether, the effect on their sales would likely be much harsher.