FDAnews Drug Daily Bulletin

REVIEWER RECOMMENDS 'NONAPPROVABLE' ACTION FOR PROVIGIL ADHD INDICATION

March 24, 2006
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An FDA reviewer is urging the agency not to approve Cephalon's bid to market its narcolepsy drug Provigil as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, arguing the drug presents unacceptable risks to that patient population.

The agency's Psychopharmacologic Drugs Advisory Committee is scheduled to convene March 23 to consider Cephalon's supplemental new drug application (sNDA) for an ADHD indication for Provigil (modafinil). The company submitted its sNDA in December 2004, and the FDA issued an approvable letter in October 2005. The agency decided to hold the advisory committee meeting to address reported risks associated with the drug, including incidents of skin rash and psychiatric adverse events.

In background documents released recently, one FDA reviewer said clinical studies show modafinil was "significantly better than placebo in terms of efficacy" for treating children and adolescents with ADHD.

But another FDA reviewer said the studies identified "worrisome safety signals," including Stevens-Johnson Syndrome and other rashes of unclear significance, a possible Reye's Syndrome case, and various psychiatric disorders such as suicidality, depression, agitation, psychosis and phobias. Other safety signals associated with the drug versus placebo included insomnia (27 percent versus 4 percent), anorexia (16 percent versus 3 percent) and headaches (20 percent versus 13 percent), the reviewer said.

"Despite the demonstration of clinical efficacy, the safety profile demonstrates increased and -- in this reviewer's opinion -- unacceptable risks to children and adolescents, resulting in the recommendation that the agency take a nonapprovable action on this submission," the reviewer said.

The FDA is not required to follow the advice of its advisers, but usually does. For background materials on the meeting, access http://www.fda.gov/oc/advisory/accalendar/2006/cder12544d032306.html (http://www.fda.gov/oc/advisory/accalendar/2006/cder12544d032306.html). (http://www.fdanews.com/did)