Transcript Batten Disease

Batten Disease
Accessing the Accelerated Approval Pathway with a
Rare Neurologic Disease
June 29-30, 2010
FDA Public Meeting
“Considerations regarding the review and
regulation of articles for treatment of rare diseases”
Tracy VanHoutan, Board Member
of the Batten Disease Support and Research Association (BDSRA)
Tracy VanHoutan
 Father of 3 children; 2 affected by Late Infantile Neuronal Ceroid
Lipofuscinosis (LINCL)-more commonly known as Batten
Disease
 Noah- Age 6, Laine- Age 4 (has fraternal twin, Emily)
 Board member of the Batten Disease Support and Research
Association (BDSRA)
What is Batten Disease?
 Neuronal Ceroid Lipofuscinosis (NCL)
 Autosomal recessive
 Ultra Rare - affecting 2-4 births out of 100,000
 10 different disorders with different defective genes
 Children develop normally until onset age, then regress
 Accumulation of waste material in the brain
 Vision loss, ataxia, seizures, loss of motor function
 Always fatal
There is no FDA approved therapy
for Batten Disease
Faces of Batten Disease
Taylor
Infantile NCL
Mary Payton
Late Infantile NCL
Hayden
Infantile NCL
Amber
Juvenile NCL
Sara
Juvenile NCL
Sandy
Juvenile NCL
Jasper
Late Infantile NCL
Bridget
Late Infantile NCL
Christiane
Juvenile NCL
Daniel
Late Infantile NCL
Diagnosis of Batten Disease?
 Retinal Exam & MRI – only useful if physician recognizes signs of
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Batten
Skin Microscopy
Enzyme Levels
 Seattle Children’s Hospital is the only testing lab in USA
 Infantile and Late Infantile versions only
Gene Sequencing
 Massachusetts General is the only testing lab in USA
Universal Carrier Screen using Next-Gen Sequencing
 Beyond Batten Disease Foundation and National Center for
Genome Resources developing inexpensive(<$500) test panel for
450+ rare childhood genetic disorders.
Future Goal: Early diagnosis leads to improved
outcomes for Batten children.
Potential Therapeutic Strategies
 Gene Therapy
 Phase I using AAV2 complete
 Phase I screening for Rh10 underway
 Stem Cell Therapy
 Phase I complete
 Phase II – application submitted to FDA
 Enzyme Replacement Therapy
 Currently under exploration
 Small Molecule Therapy
 Reduction of neuro-inflamation in LINCL & INCL
 “Noah’s Hope” and “Taylor’s Tale” funding proof of
concept studies
Therapeutic Development
 1 project currently under review with FDA
 2 projects currently recruiting patients
 6 projects in pre-clinical or proof-of-concept stage for
Batten Disease
 These project offer a very small amount of hope to parents
currently with diagnosed children.
 If they are delayed or not well understood at the regulatory level
then we could lose another generation of Batten Disease
children.
 It is one thing to be sensitive to the needs of patients with rare
fatal disorders
 We believe people trained in genetic medicine should be making
decisions on treatments for rare genetic disorders.
Developing Treatments
 Difficult disease due to neurologic problems
 Hard to measure neurologic decline in young
children
 Variable rates of progression
 Variable degrees of reversible disease
 Clinical neurologic endpoints for studies are
imprecise and variable in accuracy
Drug Development is Hampered by the
Nature of this Difficult Disease
 Neurologic damage not likely reversible
 Most patients not diagnosed until they have
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neurologic disease
Clinical endpoints may be too late to allow
assessments of a drug effectively
The populations are small and variable
These difficulties have limited development of
treatments
If we have a drug that works, can we show it?
Accelerated Approval Regulations
 Designed to assist in the early approval of drugs
that have a clear effect on a marker of disease
 Avoids the problem of waiting until patients die or in
using imprecise clinical measures that may block or
eliminate investment
 Yet only 1 genetic disease has been approved via
these regulations
 Why?
Access to Accelerated Approval
Regulations is needed for Battens
 A measure of brain injury should be sufficient to assess
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whether a very early stage baby is being improved
Given the high morbidity and serious outcomes, clinical
endpoint driven studies would be difficult to do
The rarity and lack of other clinical data prevents
Batten’s and other neurogenetic disorders from
accessing the accelerated approval pathway
Must treat before the disease has neurological effects
This pathway is not available for the diseases that need
it most, which cannot be what Congress intended
Rare and Devastating Neurogenetic
Diseases like Batten Disease Need
Access to Accelerated Approval
 Our kids have a 100 % probability of dying with
Batten Disease
 We need to figure out how to allow markers of brain
injury to be used to study new treatments in small
numbers of patients
 Allowing access to accelerated approval will spur
more investment in the difficult to study diseases like
Batten Disease and many like it
 We need survival to be better than 0%
Recommendations
1. Establish a new Office of Drug Evaluation for
Biochemical and Genetic Diseases
o Add experienced staff with appropriate genetics
expertise
o Focus on disease areas not well covered today
o Establish guidelines for rare and ultra-rare diseases
o Improve coordination between University
researchers, non-profits, private companies and NIH
to assist in translating research to patients.
Recommendations
2. Establish protocols allowing use of surrogate
endpoints, specifically, qualifying neurological
endpoints that would change the dynamic of
clinical trials and assistant with the development
of treatments
o There are no FDA approved bio-chemical end-points of
neurodegeneration at this time.
o Surrogate endpoints would not replace clinical
outcomes, but would serve as supplemental endpoints
of treatment effectiveness.
o Surrogate endpoints hold great potential for improving
clinical trial design for ultra-rare diseases.
o Acceleration and development of new treatments for
patients with no other alternatives.