Cephalon's follow-on excessive sleepiness therapy Nuvigil (armodafinil) was approved June 15 with an anticipated bolded warning about "serious rash" that might require hospitalization; a similar warning will be added to labeling for the first-generation drug Provigil (modafinil).

Nuvigil was approved for the treatment of excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome (OSAHS), narcolepsy and shift work sleep disorder. In OSAHS, Nuvigil is indicated as an adjunct to standard treatment for the underlying obstruction.

Final Nuvigil labeling includes a bolded warning that "serious rash requiring hospitalization and discontinuation of treatment has been reported in adults and children in association with the use of modafinil, a racemic mixture of S and R modafinil (the latter is armodafinil)."

In addition, the bolded warning notes that "armodafinil has not been studied in pediatric patients in any setting and is not approved for use in pediatric patients for any indication."

The company first filed the Nuvigil NDA in March 2005, but the approval was complicated by the discovery of rashes in patients enrolled in a pediatric study of modafinil as a potential therapy for attention deficit/hyperactivity disorder. FDA rejected modafinil for ADHD, known as Sparlon , because it suspected at least one rash to be a case of Stevens Johnson Syndrome (¹ Also see "Nuvigil May Be Further Delayed As FDA Reviews Side Effect Profile" - Pink Sheet, 7 December, 2006.).

Safety information in the Nuvigil label includes data from studies Cephalon conducted for Sparlon. The company also said it will update Provigil labeling with the bolded warning (² Also see "Nuvigil Draft Label Warning Includes Both Modafinil And Its Follow-On" - Pink Sheet, 30 March, 2007.).

Cephalon has a suite of clinical studies teed up to support more robust labeling for Nuvigil before it plans a commercial launch of the Provigil follow-on.

Studies examining the effectiveness of the wake-promoting agent as a therapy for bipolar depression and for cognition associated with schizophrenia, as well as for excessive sleepiness in medical conditions such as Parkinson's disease and fatigue in cancer patients all will be underway "in the very near term," the company told "The Pink Sheet" DAILY.

Cephalon began talking about the label extension strategy after patent protection for the older drug was shored up by settlements with ANDA filers that are likely to stave off generic competition until 2011 (³ Also see "Sepsis Set Back: AstraZeneca CytoFab Development Will Be Delayed Two Years" - Pink Sheet, 3 November, 2006.).

"With a broader label in hand, we will switch our marketing efforts from Provigil to Nuvigil around 2010," Cephalon CEO Frank Baldino said in November. Nuvigil is protected by patenting until 2023 (⁴ Also see "Nuvigil Gets Protection Until 2023 Under New Patent" - Pink Sheet, 9 November, 2006.).

In August, the Federal Trade Commission began an investigation of generic settlements including the deal Cephalon struck with Barr, Teva, Ranbaxy and Mylan to delay generic competition for Provigil (⁵ Also see "Cephalon Provigil Generics Settlements Under FTC Investigation" - Pink Sheet, 30 August, 2006.). "Nothing has changed" regarding that investigation, the company said June 18.

Cephalon plans to complete Phase III studies and file an NDA for its oncologic Treanda (bendamustine) for non-Hodgkin's lymphoma by the end of the year (⁶ Also see "Cephalon’s Oncologic Treanda On Track For Q4 NDA Filing" - Pink Sheet, 13 February, 2007.).

- Shirley Haley (⁷ s.haley@elsevier.com)

[Editor's note: Frank Baldino discussed the company's pipeline and strategy with "The Pink Sheet" DAILY in January (⁸ Also see "Cephalon CEO Frank Baldino: An Interview With “The Pink Sheet” DAILY" - Pink Sheet, 9 January, 2007.).]

FDA Approves Cephalon’s Nuvigil With Bolded Warning For Rash

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