Genetic Diseases of Children The Role of Orphan Drugs Marlene E. Haffner, MD, MPH 9 March

First let’s talk about drug development Complex and failure prone process Takes 5 – 10 years or more Human genome opening many doors Many if not most genetic diseases of children are orphan diseases – prevalence of rare disease is less than 200,000 in the US by law

DrugDiscoveryAnimalTesting Approval PostMarketing Human Testing Phase I Phase II Phase III years Preclinical Development year years 6 months - 1 year years $1.2 Billion New Drug Development INDNDA 3

Orphan Drug Act Amended the FD & C Act – signed in 1983 Has been very successful – almost 400 new drugs developed since signing Many more in the pipeline Children recognized Incentives in the ODA to offset cost of development for sponsors

Characteristics of a Rare Disease While < 200,000 by law, many if not most < 6000 patients in the US Many Genetic Diseases – often heterogeneous ~ 85% Serious or Life Threatening Children comprise ~ 50% Most are chronic

Development of orphan products Same as for non-orphan products Orphan products need to be as safe and as effective as non-orphan products Always must evaluate risk vs benefit Much attention given to Orphan Products in the FDA

In the realm of Genetic Diseases of Children PKU - Kuvan NAGS disease – Carbaglu Urea Cycle Disorders – Buphenyl and Ammonol SCID (ADA type) – Adagen Tyrosinemia – Orfadin WOULD NOT HAVE BEEN DEVELOPED WITHOUT THE ORPHAN DRUG ACT INCENTIVES

Many treatments, no cures Cystic Fibrosis - many products to alleviate disease Sickle Cell Disease – several alleviating treatments but no definitive therapy Human Genome project and aftermath leading to more directed products No Stem cell therapies yet Lives have been significantly and positively altered

Marlene E. Haffner, MD, MPH President & CEO Danville Drive Rockville, Maryland office cell ?