FDAnews Drug Daily Bulletin


March 27, 2006

An FDA panel of medical advisers overwhelmingly agreed that Cephalon's narcolepsy drug Provigil is not safe enough to be marketed for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents.

The agency's Psychopharmacologic Drugs Advisory Committee voted 12-1 that the drug is not safe based on the data that the company presented, said a Cephalon spokeswoman. The panel, however, also voted unanimously that the drug is effective in treating ADHD in this population.

The committee met to discuss Cephalon's supplemental new drug application to market Provigil (modafinil) under the brand name Sparlon as an ADHD treatment for children. The panel encouraged the company to present more data that could ease any uncertainties, said the spokeswoman.

"We are obviously disappointed with the recommendation of the advisory committee," said Paul Blake, executive vice president of the company's Worldwide Medical and Regulatory Operations. "We will continue our discussions with the FDA to determine the next steps in the review of this drug application."

The FDA is not required to follow an advisory panel's decision, but usually does. The agency in October 2005 issued an approvable letter for the drug.

The panel's recommendations echo the agency's split opinion on the drug. In background documents, one FDA reviewer said the drug is "significantly better than placebo" in terms of efficacy. But another reviewer said clinical studies of the drug identified "worrisome safety signals," including a serious skin rash known as Stevens-Johnson Syndrome. The drug's safety profile demonstrates "unacceptable risks to children and adolescents," said the reviewer, who urged the FDA not to approve Sparlon.

Cephalon defended the drug and said the treatment of modafinil is "generally safe and well tolerated" in children and adolescents with ADHD. The drug has been tested in 933 ADHD patients from this population group, the firm said in a document prepared for the advisory committee meeting.

The firm also said studies revealed few adverse events of "special interest" such as skin rash and psychiatric episodes. There were two cases of children with possible Stevens-Johnson Syndrome, which is manifested as skin blistering, the firm said. Neither of those patients was hospitalized. In addition, the studies found no cardiovascular safety issues. (http://www.fdanews.com/did)