Aricept Goes Generic

After 13 years as the number-one prescription treatment for Alzheimer disease, Aricept—a branded cholinesterase inhibitor that generated nearly $1.9 billion in US sales this year for its Japan-based developer Eisai and US comarketer Pfizer—is now (officially) available generically in the United States.

Yesterday the FDA announced the approval of a generic formulation of Aricept (or more correctly, donepezil) in orally disintegrating tablets. The generic manufacturer is the privately owned Mutual Pharmaceutical (URL Pharma), which will produce the drug in 5- and 10-mg strengths.

Other branded, FDA-approved treatments for AD include the NMDA-receptor antagonist memantine (Namenda; Forest) in tablets or solution and the cholinesterase inhibitors galantamine (Razadyne; Ortho-McNeil) in extended-release capsules, tablets, or solution and rivastigmine (Exelon Patch; Novartis). The patent for galantamine, originally marketed as Reminyl in the United States, expired in December 2008, and the drug is available generically in its various formulations.

According to the FDA's Orange Book, the following patent and exclusivity expirations apply to Namenda and Exelon*:

(Differences between a drug's patent and exclusivity are explained by the FDA here.)

On November 24, Eisai announced that the FDA accepted for review its NDA supporting the use of a 23-mg extended-release tablet version of Aricept in AD. The NDA is based on a head-to-head study (N > 1400) between the new formulation and the old Aricept 10-mg tablet. This study, apparently, has not been published yet in a peer-reviewed journal. In its 2009 report, Eisai also reveals that it is developing transdermal patch and jelly formulations of Aricept.

Very recent controlled studies of immediate-release Aricept in patients with amnestic mild cognitive impairment (aMCI) suggest that the drug delays the progression to AD among depressed individuals, but Aricept had only a modest effect on cognition in a more inclusive population with MCI.

NDA = new drug application; NMDA = N-methyl-D-aspartate.

* Rivastigmine is generically available in capsules; however, this formulation is no longer marketed by Novartis. It is also reported that Forest applied for a "patent term restoration" for Namenda, which would extend protection until September 2013.

Photograph: Atrophied brain from person with AD from National Institute on Alcohol Abuse and Alcoholism.