2.  Treats a population of < 200,000 in the US  Same review and development standards as for a non- orphan product  Numbers of patients in clinical trials will be smaller  FDA has two special units to deal with orphan products Office of Orphan Products Development/Office of the Commissioner Associate Director for Orphan Products in the Office of New Drugs (OND)/CDER

3.  7 years exclusive marketing for that drug for that disease  Tax credits for clinical development – 20 yr carry forward; 1 year fall back  Waiver of NDA filing fees ($1.5 million FY 2011)  Grant support - $450,000/annum for 4 years

4.  More than 7,000 rare diseases  More than 350 drugs for orphan diseases have been developed since 1983  Burgeoning field – large and small companies involved  Money to be made  Review times may be faster as majority of orphan diseases serious or life threatening

5.  Measure of effect of effect of treatment that may correlate with a real endpoint  No guaranteed relationship  Needs validation  E.g. cholesterol is related to heart disease, but many with high cholesterol do not develop heart disease.  So cholesterol lowering drugs lower cholesterol but that alone does not prevent death. Proof of efficacy in preventing heart disease took 5 years to show.

6.  May be able to shorten a clinical trial with the us of VALIDATED endpoints  Great interest currently; may not correlate

7.  Indicates a disease state or some physiological state of the organism  May be used to measure the progression of disease or the effects of treatment  Rheumatoid Factors as a marker for Rheumatoid Arthritis; elevated PSA for prostate cancer  May relate to how a drug will/will not act in the body – KRAS gene expression in Colorectal Cancer

8.  May assist in identifying high-risk individuals so they can either be treated prior to onset of disease of shortly thereafter  Test must be rapidly available and easy to carry out  Must be validated and related to a positive outcome

9.  Treatment of Serious or life-threatening illness  Must have meaningful benefit over existing therapies  May utilize a surrogate endpoint that is “reasonably likely…to predict clinical benefit”  May have restricted prescribing  Most likely will have post marketing requirements

10.  Must address a serious or life threatening illness  Potential to treat unmet need  Multiple meetings with FDA to discuss development plans  Options to submit sections of the NDA/BLA as they are ready

11.  Begins on submission of NDA/BLA  Shortens review time from 10 months to 6 months  May also have “Fast Track”