Obtaining Orphan Product Designation Challenges and pitfalls

1. Obtaining Orphan Product Designation Challenges and pitfalls Marlene E. Haffner, MD, MPH President and CEO Haffner Associates, LLC mhaffner3@verizon.net

2. Requirements for Designation • Population less than 200,000 in the US • Reasonable consideration that the product will have utility for the stated indication • Need some data – preferably clinical or animal • IND helpful but not a requirement

3. Obtaining your designation • Orphan Products “tip sheet” • http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/HowtoapplyforOrphanProductDesignation/ucm135122.htm • Aka – www.fda.gov/orphan - how to apply for orphan products designation

4. What is the Disease – what is a subset • Define the disease • Is that what you are treating or are you treating a symptom of the disease? • What is a subset of a disease? A part of a disease that can be treated by the drug. However, the disease as a whole cannot be treated by the drug. WHY??

5. When is a subset valid • NOT because that is what you wish to study • Because the drug is not useful for the “larger” disease • It is too toxic • Genetic markers make it ineffective – HER2 +, KRAS mutant – except in the subset • More effective treatments for other segments of the disease – surgery for stage 1 • Pediatric manifestations of a disease are valid

6. Not always straightforward • Erythropoietin for anemia of: • ESRD • Anemia of prematurity • Blackfan Diamond syndrome • Product for obesity in • Obese adults • Prader Willi syndrome

7. How is subsetting determined • Review the disease • What is the mechanism of action in the disease • Are you treating the disease or a symptom of the disease – if a symptom, then is the symptom prevalence attributed only to “that” disease – post-op pain vs pain

8. Defining Prevalence • If an oncology drug – NIH SEER Data – http://Seer.cancer.gov • If a metabolic disease – published literature; Mendelianinheritance (McKusick) – www.OMIM.org • If infectious disease – start with CDC • Sometimes hospital discharge summaries • All other – published literature – texts and current articles in peer reviewed literature • Not always easy

9. Establishing Prevalence • Use of experts – only in VERY rare diseases • Discuss issues of defining prevalence in your designation request • Be straightforward. The OOPD (Office of Orphan Products Development) reads the literature • If a range – OOPD will assume upper end • Importance in higher numbers - >100,000

10. Non Profitability in 7 years • Has occurred only 3 times since 1983 • Twice for products to treat narcotic addiction • Once for a product already marketed for another indication and about to go off patent • Difficult hurdle; must open books for review • Developing an unprofitable product is “not the usual.”

11. THANK YOU ?