ACRP 2012 Global Conference & Exhibition
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Transcript of ACRP 2012 Global Conference & Exhibition
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Strategic Clinical Innova1on
April 15, 2012
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Candida Fratazzi MD President
BBCR, LLC www.bostonclinicalresearch.com
Rising interest in the Rare Disease model could have a cri1cal role into Biomarker’s implementa1on
for Stra1fied Medicine
S023 room 350 D-‐F 10:30-‐ 11:30AM
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• Understand drug development challenges
• Biomarkers per pa1ents selec1on and efficacy evalua1on: an orphan disease case study
• Discuss strategic clinical innova1on and stra1fied medicine
Learning Objec1ves
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Innova1ve Strategies are overdue
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• Gaps, that cost 1me and money, appear in the clinical research process
• Protocols wriVen for top line visualiza1on that may be lacking scien1fic rigor
• Clinical strategies and plans may be myopic and miss greater op1ons
• Increasing regulatory demand for transparent study results and cross AEs
Which are the causes
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S t r a t e g y a n d I n n o v a1on
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Focus on clinical strategy, early plan and study design
Bridging research and clinical trials
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• Links preclinical data with unmeet medical needs
• Matches study endpoints with study objec1ves • Connects product poten1al to treatment benefits
• Creates cohesive phase I/II studies to support first in man/POC objec1ves
Strategic Clinical Innova1on is a bridge
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Bridging the Chasm
Pre-‐clinical research meets FPI
Discovery / Pre-‐Clinical
Protocol Im
plem
enta:o
n/CR
O
Strategy
Safety / Tox Data
Discovery Data
Biomarkers Trial Design
Objec1ves/ Endpoints
Pa1ents Selec1on
Pa1ents Safety
Regula1on Disease Staging/ KOL
Protocol Synopsis
Pa1ents’ Needs
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S t r a 1fi ed Med i c i n e i s t h e g o a l
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Choose the RIGHT DRUG at the RIGHT DOSE for the RIGHT GROUP OF PEOPLE
Non-Responders
Responders
Adverse Drug Events
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Beneficial to some
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Harmful to others
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• Avoid adverse events Ø 2.2 million people are hospitalized and 100,000
deaths occur each year due to adverse effects of prescrip1on drugs
• BeFer treat disease Ø Development of predic1ve markers would allow for
earlier treatment • Iden:fy novel drug targets
Ø Current drugs are based on less than 500 targets
Advantages of Stra1fied Medicine
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B i oma r k e r s a r e t h e t o o l s
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Why Biomarkers are important
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A molecule that indicates an altera1on of the physiological state of an individual in rela1onship to health or disease state,
drug treatment, toxins etc.
Biomarkers are, by virtue of their short term availability, predictors of long term events
Biomarker defini1on
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Biomarkers connect
Qualified biomarkers
Biology Clinical endpoints
A qualified biomarker must link biology and clinical end-points
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• Screening markers: markers discrimina1ng the healthy state from beginning of disease state preferen1ally in an asymptoma1c phase ( cancer makers for early diagnos1c)
• Prognos:c markers: once the disease state is established predict the likely course of the disease
Different types of biomarkers
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• Stra:fica:on markers: predict the likelihood of a response to a drug before star1ng treatment classifying pa1ents in “responders” and “non-‐responders”
• Efficacy markers: monitor the efficacy of a drug treatment
Different types of biomarkers
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Biomarkers in clinical innova1on
• Biomarkers that validate the importance of the target in human disease
• Biomarkers that define the direct interac1on of the compound with its discrete target
• Biomarkers that define consequences of compound interac1on with the target rela1ve to PK
• Biomarkers that correlate with disease • Biomarkers that define likelihood of pa1ents to respond
(or not) to the compound
Target/Compound Interac1on Pharmacodynamic Ac1vity (PK/PD)
Target Valida1on
Disease Biomarker & Disease Modifica1on Pa1ent selec1on and Stra1fica1on
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O r p h an D i s e a s e i s t h e mode l : C a s e S t u d y
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Challenge Develop the new ERT in an orphan popula1on when a very similar product had the market monopoly for about 15 years
• Very limited number of naïve pa1ents
• Newly diagnosed pa1ents presented with early symptoms
• Treated pa1ents had improvement on many of the clinical features
Gaucher disease Type 1
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Strategy Create a clinical innova1ve strategy and trial designs, which would require a feasible number of pa1ents, and 1ght pa1ents’ selec1on with study endpoints. Select validated biomarkers’ assay with known intra-‐assay and intra-‐personal variability. Work with the Regulatory agency upfront to validate approach. Understand physicians and pa1ents expecta1ons versus current standards of care.
Gaucher disease Type 1
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• Rare disease with a prevalence 1:50,000-‐ 100,000; Type 1 is the most common Gaucher variant
• Disease expression varies from asymptoma1c to significant morbidity
• Disease progression in Type 1 Gaucher disease occurs over decades, possibly shortens life expectancy
Gaucher Disease
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• Inherited deficiency of lysosomal enzyme glucocerebrosidase (GCD)
• Accumula1on of glucocerebroside in macrophage lysosomes (liver, spleen, bone marrow, brain)
• 3 variants: type 1, 2, and 3
Gaucher Disease
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• Hepatosplenomegaly
• Hypersplenism
• Hematological abnormali1es (anemia, thrombocytopenia)
• Lung disease • Bone disease (pain crises, fractures, osteonecrosis) • Non-‐neuronopathic (Types 2 & 3 are neuronopathic)
Gaucher Disease type 1 -‐ Clinical Features
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• Change from baseline
– Hemoglobin
– Platelet count – Spleen volume
– Liver volume
Study Endpoints
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The proposed clinical strategy was successful, and the product was approved
Summary
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• Overall clinical development program well planned
• Clinically meaningful endpoints
– Natural history well understood • Each trial had a dis1nct purpose – studies supported an1cipated use in both treatment naïve and switching pa1ents
Clinical Strategy Success
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C o n c l u s i o n
Sample pre-‐1tle
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Safer and more Effec1ve drugs
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• Develop Early Roadmap
• Create Strategic Clinical Plan • Customize trial design
• Op1mize pa1ent selec1on
• Visualize goals, ac1on plan and op1ons • Maximize early stage product-‐value
Strategic Clinical Innova1on approach
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• Accelerate enrolment
• Increase inves1gators’ interest • Facilitate IRB approval • Reduce pa1ents withdrawn from the study
• Reduce blames for bad trial execu1on
• Increase study success rate
Strategic Clinical Innova1on advantages
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Que s t i o n s ? ? !
Sample pre-‐1tle
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Disclosure
I have no relevant financial rela1onship
in rela1on to this educa1onal ac1vity