Obtaining Orphan Product Designation Challenges and pitfalls Marlene E. Haffner, MD, MPH President and CEO Haffner Associates, LLC

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 2

Obtaining your designation Orphan Products “tip sheet” oductsforRareDiseasesConditions/Howtoapp lyforOrphanProductDesignation/ucm htmhttp:// oductsforRareDiseasesConditions/Howtoapp lyforOrphanProductDesignation/ucm htm Aka – - how to apply for orphan products designationwww.fda.gov/orphan 3

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?? 4

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 5

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

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 7

Defining Prevalence If an oncology drug – NIH SEER Data – If a metabolic disease – published literature; Mendelian inheritance (McKusick) – 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 8

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 9

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.” 10

THANK YOU ? 11

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