Re-Purposing Drugs as Orphans

By Dr. Tim Cote

The notion of taking an already-licensed drug, usually for a common disease, and developing it for a rare disease (orphan) indication is extremely attractive to many start-ups who want to join the orphan drug gold rush.  While every case has its own peculiarities, there are some thematic upsides and downsides to this approach in drug development.

Upside: A drug that is already on the market is clearly a pharmo-active substance---it was demonstrated to the regulators to be effective for some other indication at doses that demonstrated acceptable levels of safety.  (NB: remember, of course, that what’s acceptable safety is partially dependent on the indication under consideration. What’s safe for a cancer treatment isn’t necessarily safe for a headache).  The already-licensed drug likely has completed all the toxicity studies required.  The manufacturing conundrums have been solved.  It may even be off-patent, yet, (with orphan exclusivity) be ready for a new life under your market protection.  Here we have an off-the-shelf drug all ready for easy entry into clinical trials by that eager KOL ready to publish the academic paper with data that can secure your new NDA (sans PDUFA fee).  Sounds great, yes?

Downside: The real incentive of the orphan drug pathway is that orphan exclusivity results in the ability to set high price points.  Repurpose an existing product for an orphan indication and yes, you and you alone will exclusively be licensed to promote your product for that rare disease indication.  You will be the only one with the label for that rare disease.  But substitution at the point of care is completely legal----FDA does not regulate the practice of medicine or pharmacy (the state Boards do).  If your product has a typical orphan drug price point, it is likely that the drug you repurposed will be substituted at the point of care, making all your work for naught.

Repurposing is a venture that is scientifically seductive but commercially complicated.  Work-arounds to these commercial complications can be found (especially) with changes in the route of administration or dose preparations, but it isn’t easy.  Again, every one of these ideas is a one-off particular, and the details matter - lots.  If you’d like to talk about your latest brainstorm, email Tim at