FDA Committee Rejects ADHD use for Modafinil

RENEE MONTAGNE, host:

An expert panel has advised the Food and Drug Administration not to approve a new drug for attention deficit hyperactivity disorder. Panel members say the drug isn't safe enough to give to millions of children.

NPR's Jon Hamilton reports.

JON HAMILTON reporting:

Modafinil is already approved for people with sleep disorders. It helps them stay alert. The company that makes Modafinil, Cephalon, was hoping to expand into the much larger market for ADHD drugs. The advisory panel has dimmed that hope.

Its recommendation came at the end of an all-day meeting in Gaithersburg, Maryland. But the tone was set by the day's first speaker. Dr. Glen Manheim(ph), an FDA scientist, described children who developed severe skin rashes after taking Modafinil.

Mr. GLEN MANHEIM (scientist for the Food and Drug Administration): One subject had peeling and blistering over the entire body, with lips and urinary tract involvement. The drug was stopped, but the rash progressed to involve peeling, blistering, mucosal involvement, over days.

HAMILTON: Manheim said the drug appeared to have caused an extremely rare skin problem called Stevens-Johnson syndrome. This was a mild case, but Manheim says the condition often requires treatment in a hospital burn unit, and some patients die.

Manheim says there might be big problems if even 10 percent of the 2.5 million children on ADHD drugs switched to Modafinil.

Mr. MANHEIM: Based on the known mortality associated with (unintelligible) with Steven-Johnson, we would expect from 25 to over 400 deaths to occur.

HAMILTON: Other FDA officials were less concerned. And Cephalon argued that millions of people around the world have taken the drug without problems.

It was also unclear just how many children had actually developed severe skin problems. Dr. Daniel Pine, a panel member from the National Institutes of Health, asked for help during the discussion.

Dr. DANIEL PINE (Chief, Section on Development and Affective Neuroscience): So do we have three cases where everybody would agree that these are concerning dermatologic issues? Do we have one case? Do we have two that are somewhat concerning, a third that's suggestive? And, you know, can we get some agreement on that?

HAMILTON: In the end, the panelists could only agree about the one case. And records showed the boy's skin condition never even kept him home from school.

The panelists also heard an impassioned plea from Dr. Joseph Biederman, a Harvard Psychiatrist who's done research on Modafinil for Cephalon. Biederman says ADHD patients need choices beyond the traditional stimulants they're usually prescribed.

Dr. JOSEPH BIEDERMAN (Professor of Psychiatry, Harvard Medical School): Although the stimulants are clearly an effective treatment for ADHD, a sizable number, in the order of 40 percent are non-responsive or not tolerating this treatment, calling for alternative treatment for this condition.

HAMILTON: Ultimately, the panel took the cautious road. Twelve of thirteen panelists said the FDA should not approve Modafinil.

Their recommendation came a day after a different FDA committee heard a litany of concerns about existing drugs for ADHD. These drugs have been linked to heart problems and suicidal thoughts. The recommendation is a major blow for the drug company, Cephalon. Gary Nachman is a pharmaceutical analyst for the investment company, Leerink. He said approval would have meant a lot of money for Cephalon.

Mr. GARY NACHMAN (Director Analyst, Equity Research at Leerink Swann & Company): I forecast sales of about 120 million this year, growing to a little bit over 400 million in 2010. And, at that point, it would represent about 20 to 25 percent of the company's total sales.

HAMILTON: Nachman said the FDA panel didn't slam the door on Modafinil. Members suggested that a new study of several thousand children could show whether severe skin problems are a major issue or just a rare occurrence.

Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.