FDA Reaffirms 5-year Exclusivity for a Pro-drug

FDA has reaffirmed its prior assignment of 5 years exclusivity to Vyvance (lisdexamfetamine dimesylate).  When Vyvance was approved in 2007, this prodrug of dextramphetamine was given NCE status with a 5 year exclusivity.  With this exclusivity, the FDA may not accept an ANDA before the exclusivity expires unless a paragraph IV is filed, in which case the ANDA may be filed 1 year prior to the expiration of the exclusivity.

Actavis filed an ANDA on 1/28/2009 with a paragraph IV certification.   FDA refused to file this ANDA on the grounds that it was too early.  Actavis sued the FDA in the D.C. District court. (see Actavis complaint re: Vyvance )  This complaint argues that FDA made an error of law in granting the NCE status.

FDA opened a public docket in April 2009.  Last week, FDA confirmed (fda-2009-n-0184-00341) that lisdexamfetamine is entitled to NCE exclusivity. The FDA stated:

Lisdexamfetamine is a prodrug that is metabolically converted to produce dextroamphetamine, which is responsible for the drug’s activity. Under FDA’s regulation at 21 CFR § 314.108, a non-ester covalently bonded molecule is considered the active moiety ofa drug and, if not previously approved, it will be considered a new chemical entity entitled to 5 years of exclusivity. A non-ester that requires metabolic conversion to produce a previously approved active moiety is considered a new chemical entity. Because lisdexamfetamine is a non-ester covalently bonded molecule, and because it requires metabolic conversion to produce dextroamphetamine, lisdexamfetamine is a new chemical entity and is thus entitled to 5 years of exclusivity.

Camargo has worked on a number of prodrugs and we have found that  FDA is consistent in how it makes the determination.