FDA Panel Says Risks Outweigh Benefits On Two Asthma Drugs

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Main Category: Respiratory / Asthma
Also Included In: Regulatory Affairs / Drug Approvals
Article Date: 12 Dec 2008 - 0:00 PDT

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A panel of experts that advises the US Food and Drug Administration (FDA) on drug safety said on Thursday that two drugs currently approved for the treatment asthma and chronic obstructive pulmonary disease (COPD) have too high a risk of asthma-related adverse reactions and death when used without a steroid, and these risks outweigh the benefits for children, adolescent and adult patients. The panel vote on the resolution was unanimous in the case of children.

The two drugs are the single-agent long acting beta2 agonist inhalers salmeterol (GlaxoSmithKline PLC's Serevent) and formoterol (Novartis AG's Foradil). If the FDA follows the panel advice and withdraws approval for asthma treatment, the two drugs would still be indicated for treatment of COPD, which accounts for about half their current use, said a report in MedPage Today. The FDA does not have to follow the recommendations of its advisory panels, but it usually does.

Two other more widely used drugs, Glaxo's Advair (contains active agents fluticasone and salmeterol) and AstraZeneca PLC's Symbicort (contains active agents budesonide and formoterol) are still considered safe for asthma patients of all ages, said the panel, because they contain a corticosteroid, which appears to compensate for the risk posed by long-acting beta agonists.

In the case of salmeterol (Serevent), the FDA panel voted 17 to 10 that the benefits did not outweigh the risks for adults (18 years old and over), 21 to 6 for adolescents (12 to 17 years), and 27 to 0 for children (4 to 11 years).

In the case of formoterol (Foradil), the FDA panel voting was nearly the same as for salmeterol (Serevent), the exception being one vote difference in the case of adults where the panel voted 18 to 9 that the benefits did not outweigh the risks.

The FDA panel comprised the Pulmonary-Allergy Drugs Advisory Committee, the Drug Safety and Risk Management Advisory Committee, and the Pediatric Advisory Committee. It met for two days during which the members reviewed evidence on the safety and efficacy of the four drugs, including an FDA metanalysis of 110 trials that showed patients taking salmeterol (Serevent) had a higher statistically significant risk of hospitalization and death.

The black box warnings on salmeterol (Serevent) and formoterol (Foradil) already state they should be used together with a corticosteroid, but the panel reviewed evidence showing that nearly 50 per cent of patients take them without the corticosteroid.

Novartis and Schering-Plough (joint marketers of Foradil in the US) said they strongly disagreed with the panel's view on Foradil. In a statement reported by WebMD, they said:

"We believe this opinion is inconsistent with clinical evidence supporting the benefit/risk profile of Foradil in patients not adequately controlled on other asthma-controller treatments."

According to MedPage Today, the companies said it was important that doctors had access to single agent long lasting beta agonists so they could develop customized treatments according to the needs of their patients. The benefits did not outweigh the risks in the treatment of asthma when the drugs were used as specified on the current label, they said.

However, one comment has been made that the black box warning does not mention having to use the drugs with a corticosteroid until after the first paragraph, and many people don't bother to read much further.

Sources: WebMD, MedPage Today.

Written by: Catharine Paddock, PhD


Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today