ICORD 2009: Facilitating Cooperation in Regulatory Efforts Timothy Cote, MD MPH Director, FDA Office of Orphan Products Development, Food and Drug Administration, Rockville, MD, USA Monday, Feb 23, 2009

International Collaborative Regulatory Actions Designations  The joint form  Annual reports  Exchange Grants Neglected tropical diseases The Science of Small Clinical Trails Search for Forgotten Orphan Drugs of Special Promise---We must be accountable in holding the People’s data.

The search for forgotten orphan drugs of promise 25 years! 1,892 orphan designations as of August 2008 (1,960+ now) and 334 marketing approvals---what happened to the rest? Some were junk. Some were toxic. Some were forgotten. Drug development is not a strictly Darwinian process where the fit (i.e. safe/effective) always win.

Definition: Forgotten Orphan Drugs? Some IND* data was submitted to FDA IND was begun before Jan No record of recent activity on the IND. Hasn’t been approved for  its designated orphan indication,  another orphan indication  or a common disease  (i.e. not on the market). *Investigational New Drug, a file of incoming data submitted to FDA.

1892 Designations 1983 through 8/31/ Approved Orphan Indication 361 Recent INDs 2006 through 8/31/ No IND Available 137 Approved For another Orphan Indication 572 Older Designations, Not-Approved with an IND 179 Approved For a Common Disease Indication 23 Other INDs Status 88 CBER Biologics 59 WithdrawnI NDs 26 Terminated INDs 70 Inactive INDs 306 Active INDs 266 Forgotten Orphans Forgotten Orphans Waiting at FDA

Plan: Re-examine Forgotten Orphans Study design Study enrollment Study results for Efficacy Study safety signals Then…if there are forgotten orphans of great promise; reinvigorate them!

Summary: Rare Diseases Erase National Boundaries International body of science International pharmaceutical industry International network of patients To be effective proponents of developing drugs for rare diseases, regulators must work internationally.