Washington Editor

After revealing favorable results from three multicenter clinical trials of modafinil in attention deficit hyperactivity disorder in children and adolescents, Cephalon Inc. said it expects to seek regulatory approval earlier than previously stated.

Cephalon anticipates filing its application during the fourth quarter of 2004 rather than the first quarter of 2005, Chip Merritt, Cephalon's senior director of investor relations, told BioWorld Today.

Modafinil, first approved in 1998 under the name Provigil as a treatment for narcolepsy, also is sold in the U.S. as a treatment for excessive sleepiness associated with obstructive sleep apnea and shift-work sleep disorder. Cephalon expects to sell the product under a different name in the attention deficit hyperactivity disorder (ADHD) in children and adolescents indication.

If the application is filed late this year, Merritt believes Cephalon could launch the product in the new indication in late 2005 or early 2006.

FDA approval in ADHD is expected to make a significant difference in modafinil sales, Merritt said, adding that even though modafinil is approved, the FDA prohibits Cephalon from marketing the drug off-label in the proposed indication.

In 2003, worldwide sales of Provigil totaled $290 million, and for the first two quarters of 2004, sales were $196 million. (The company began marketing Provigil in obstructive sleep apnea and shift-work sleep disorder in early 2004.)

Louis Webb, managing director at WR Hambrecht + Co. in New York, said the U.S. ADHD market is about $1.5 billion annually. While he did not have estimates of potential modafinil sales in the indication, he said it appears that the candidate has a promising role to play in ADHD and other indications.

Indeed, in the three trials released Thursday, all of the modafinil-treated groups showed a highly statistically significant improvement on the primary endpoint compared to placebo (p<0.0001), the company said. The primary endpoint was the teacher-completed school version of the ADHD Rating Scale IV.

The nine-week trials were double-blind, placebo-controlled studies of 600 children and adolescents between the ages of 6 and 17.

Data indicated that children responded better to higher doses of modafinil than adults, Merritt said. As a result, the company has developed dosage strengths of 340 mg and 425 mg. By comparison, adults usually take about 200 mg of Provigil.

Modafinil was generally well tolerated, and the most common side effects observed in the studies were consistent with those observed in other studies of the compound, including insomnia, headache and loss of appetite. Complete Phase III study data are expected to be presented at medical meetings over the next 12 months.

Beyond ADHD, Provigil is not being studied in any other indications. Instead, Cephalon is evaluating Nuvigil, the second generation of Provigil, in narcolepsy, obstructive sleep apnea and shift-work sleep disorder. Phase III trials in those indications are expected to wrap at the end of the year, Merritt said.

Meanwhile, Cephalon recently paid $400 million in cash to purchase all the outstanding shares ($34 per share) of CIMA Labs Inc., of Eden Prairie, Minn. CIMA now is a wholly owned subsidiary of Cephalon. The merger closed last week.

At the time of the acquisition, CIMA had been enrolling a Phase III study of OraVescent Fentanyl for cancer pain. Cephalon expects to seek regulatory approval of the product in 2005. It is believed that OraVescent Fentanyl will complement Actiq (oral transmucosal fentanyl citrate), Cephalon's marketed therapy for the condition.

Cephalon's stock (NASDAQ:CEPH) increased 12 cents Thursday to close at $45.57.