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505(b)(2) with Orphan Indication

I was recently asked how you can have a 505(b)(2) application for an Orphan drug.  The reasoning behind the query was that Orphan drugs are new chemical entities (NCE).  This perpetuates the misconception that 505(b)(2) cannot be used for NCEs, which by now readers of this blog know is wrong.  We have discussed the use of 505(b)(2) for DESI products, which, by definition are unapproved drugs (meaning that a submission of these drugs gets 5 years exclusivity because they are NCEs).

Need an example of an Orphan drug aproved under 505(b)(2)?  How about the 1999 approval of caffeine citrate (Cafcit®) for apnea of prematurity.  I’ll wait until you choke on your last gulp of coffee.  Caffeine? Yes, a NCE.   Apnea of prematurity – an Orphan indication (presumably, in treating the premature baby the mother is known, so the babies are not orphans).  This product has since gone generic.  I use this example in my 505(b)(2) workshops to lighten the mood (near coffee breaks).

Can you take an existing approved drug and re-position it for with an Orphan designation?  Sure.  You need to keep in mind how the existing drug might cannibalize your sales, but generally you make significant changes to the dose (often route of administration).  A company that appears to use the 505(b)(2)/Orphan route is TheraQuest Biosciences.  In 2005, TheraQuest received Orphan designation of tramadol hydrochloride for management of postherpetic neuralgia and treatment of painful HIV-associated neuropathy.  According to the TheraQuest’s web site, the product being developed is a once-a-day sustained-release product.



The reward of an approved Orphan is 7 years marketing exclusivity.