NOT-APPROVABLE ACTION RECOMMENDED FOR ADHD PATCH

A proposed drug patch to treat attention-deficit/hyperactivity disorder (ADHD) poses safety risks and should not be approved by the FDA, according to an agency scientist who reviewed the product application submitted by Shire Pharmaceuticals and Noven Pharmaceuticals.

The firms are seeking FDA approval for Daytrana (methylphenidate), an investigational transdermal patch designed for once-daily use to treat ADHD in children 6 to 12 years of age. All currently approved ADHD drugs, including Shire's Adderall (amphetamine aspartate/dextroamphetamine saccharate), must be taken orally.

While Daytrana represents a potential breakthrough in ADHD drug delivery, FDA review staff have yet to be convinced that the product is safe. The drug "was associated with an adverse event profile and potential risks that could pose clinically important risks to a significant number of pediatric patients who might be exposed to [methylphenidate transdermal system]," FDA clinical reviewer Robert Levin states in briefing documents recently posted to the agency's website.

Levin's clinical review and other briefing materials were made available in advance of today's meeting of the FDA's Psychopharmacologic Drugs Advisory Committee, which is convening to review Shire and Noven's new drug application (NDA) for Daytrana.

Among Levin's primary concerns with Daytrana, which would be worn against the skin for up to eight hours a day, was that the patch "was associated with a high incidence of insomnia, anorexia or decreased appetite, headache, and gastrointestinal symptoms including vomiting, nausea, and upper abdominal pain." Daytrana was also associated with a relatively high risk of developing tic disorder, Levin said.

Shire and Noven, in briefing documents posted by the FDA, argued that other stimulant drugs approved to treat ADHD, including Johnson & Johnson's popular drug Concerta (methylphenidate HCl), cause many of the same side effects as Daytrana. However, Levin said clinical data showed that adverse events were "significantly more common" in the Daytrana group than in patients taking Concerta or a placebo.

Assuming the FDA agrees with Levin's assessment and decides against approving the drug, it would mark the second not-approvable decision for Daytrana within three years.

The agency rejected Shire and Noven's NDA in April 2003 after identifying concerns about dosing, duration of wear and incidence of side effects.
To view the FDA's briefing documents, go to http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4195B-index-with-disclaimer.htm.