Welcome to Workshop #5: Accelerated Approval (AA) in Rare Diseases: Review of a White Paper Proposal. Emil D. Kakkis, M.D., Ph.D. President and Founder EveryLife Foundation for Rare Diseases May 15, 2013 Sofitel Hotel Washington, D.C. Lafayette Square.
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Emil D. Kakkis, M.D., Ph.D.
President and Founder
EveryLife Foundation for Rare Diseases
May 15, 2013
Sofitel Hotel Washington, D.C. Lafayette Square
Formed to focus on improving the development of treatments of rare diseases in February 2009
Conducting workshops and participating in conferences to help promote scientifically sound change
Supporter of ULTRA/FAST legislation in FDASIA
Working toward scientifically sound change to improve the accessibility of the Accelerated Approval pathway
181 Partners+The EveryLife Foundation For Rare Diseases
Find slides from prior workshops at
How do we practically qualify biomarkers for use with little prior clinical experience?
In FDASIA (PDUFA V) of rare diseases in February 2009US Congress Legislation: H.R. 4132: FASTIntroduced By Rep. Stearns and TownesBetter access to Accelerated Approval Pathway
“Considerations. – In developing the guidance . . . . the Secretary shall consider . . . . for drugs designated for a rare disease or condition under section 526 of the Federal, Food, Drug, and Cosmetic Act; and
(2) how to incorporate novel approaches to the review of surrogate endpoints based on pathophysiologic and pharmacologic evidence in such guidance, especially in instances where the low prevalence of a disease renders the existence or collection of other types of data unlikely or impractical.”
At Workshop #4, created the plan
Work Shop #5 Key Goal
Marc Boutin National Health Council
Susan Boynton Shire HGT
Mladen Bozic Shire HGT
Gerald Cox Genzyme, A Sanofi Company
Pat Furlong Parent Project MD
Mark Hayes Synageva
Emil Kakkis EveryLife Foundation for Rare Diseases
Cori Leonard Ultragenyx Pharmaceutical
Rachel Mack Vertex Pharmaceuticals Inc.
Mary O'Donovan BioMarin
May Orfali Pfizer
Mark Thornton Sarcoma Foundation of America
Jack Weet Seaside Therapeutics
Fleming concepts valid but not experimentally defined
Need a practical implementation of concepts
“Reasonably likely to predict clinical benefit”
White Paper Table of Contents Pathway
Emil D. Kakkis, M.D., Ph.D.
President, EveryLife Foundation for Rare Diseases
CEO, Ultragenyx Pharmaceutical Inc.
A. DISEASE CONSIDERATIONS
B. DRUG CONSIDERATIONS
C. BIOMARKER CONSIDERATIONS
D. PRECLINICALData CONSIDERATIONS
E. CLINICAL DATA CONSIDERATIONS FOR BIOMARKER QUALIFICATION
The more known is about the disease and how it causes clinical problems, the more confidence exists in the direct link to the drug and the biomarker measuring the disease
High Phe level
[ Blood Phe]
59 uM 360-2500 uM
10x to 50x
Degree of long-term
Measure Blood Phe Level
PAH in Liver
Brain injury reduced
due to lower Phe level
[ Blood Phe]
Enzyme replacement therapy (ERT) for MPS 1 the protein
Enzyme reaches target and delivered to site of action
Filled with MPS
Measuring a disease process, reliably and accurately with a biomarker directly line of the disease process.
Will CSF Samples
Reflect the brain?
Storage in neurons, glia
Microglia and meninges
Multiple cell type storage
In Cells & LSD
Tissue fluid to CSF
Compartment: Does Urinary GAG reflect tissue storage and outcome?
Clinical Outcome Improved
[ Cell Rupture]
[ Cell storage]
Data: Dickson Laboratory work using Zacharon Pharmaceuticals SensiPro Assay
CSF samples do reflect the brain compartment metabolically the proteinPreclinical Intrathecal enzyme replacement provides the therapeutic predictive insight
How will be successfully develop treatments for neuronal storage diseases?
Presentations the protein
For Rare Diseases