FDA Warning Letter Cites Cephalon For Broadening Provigil Indications

Promotion incorrectly suggests modafinil is safe and effective for various disorders associated with fatigue and sleepiness, DDMAC says.

A handout distributed on behalf of Cephalon to the Maryland Department of Health and Mental Hygiene's Pharmacy and Therapeutics Committee suggests uses for Provigil (modafinil) that have not been approved, broadening the indication for the excessive sleepiness drug, according to FDA's Division of Drug Marketing, Advertising and Communications. The agency issued a warning letter to Cephalon Feb. 27 and posted it online March 1.

The piece "creates new 'intended uses' for Provigil for which the product lacks adequate directions, broadens the indication of Provigil and fails to communicate any risks associated with its use," FDA says.

Provigil is indicated to improve wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder.

However, the document, "The Utility of Provigil (modafinil) in the Medical and Psychiatric Population," handed out by Harry Kerasidis, MD, at a public meeting discussing its inclusion on the Preferred Drug List, states Provigil "also has utility in the treatment of other neurologic and psychiatric disorders associated with fatigue, sleepiness or inattentiveness."

The handout then points to multiple sclerosis-related fatigue, Parkinson's disease-related fatigue, chronic fatique syndrome, attention deficit disorder and depression.

"Provigil is not indicated for insomnia or fatigue, which refers to a loss of desire or ability to perform, an outcome that was not directly examined in the clinical studies supporting Provigil's approval," FDA says. "Provigil also is not indicated for the treatment of any of the neurologic or psychiatric disorders cited above."

FDA says it finds the statements "particularly troubling" because Cephalon received a "not approvable" letter from the agency prior to the meeting related to expanded indications for modafinil.

In August, Cephalon announced it was halting development of modafinil for attention deficit/hyperactivity disorder after it received a "not approvable" letter due to a suspected case of Stevens Johnson Syndrome (¹ (Also see "Spar-Gone: Cephalon Drops Sparlon Following "Non-Approvable" Letter" - Pink Sheet, 9 Aug, 2006.)).

In addition, FDA points to statements in the promotional piece suggesting Provigil can improve consequences, including driving-related accidents, of a condition referred to as "sleep disorder related fatigue."

"Your presentation of these claims in this promotional piece for Provigil misleadingly implies that Provigil is proven to be effective in treating SDRF when ... Provigil is not indicated for the treatment of fatigue, which would include SDRF," the agency says.

The piece also fails to provide risk information, including a recommendation in labeling that patients taking the drug be assessed frequently for sleepiness and avoid driving if appropriate, according to the letter.

Cephalon has until March 12 to respond to the letter.

However, the company told "The Pink Sheet" DAILY that the handout was neither a Cephalon document nor one the company's personnel have distributed.

"We agree with the FDA that the document is egregious," Cephalon said. Kerasidis, the presenting MD, was speaking on behalf of Cephalon, the firm acknowledged, but "he was giving an on-label presentation and had independently prepared the document."

Cephalon said it will respond to the letter "shortly, based on what we have learned about this situation."

The warning letter is not the first time Cephalon has been cited by FDA for promotions conveying that Provigil can be used for the treatment of broader sleepiness indications. The company received a warning letter from FDA in 2002, also related to misleading claims for Provigil.

- Jessica Merrill ([email protected])