Building Consortia for Enhanced Predictive, Diagnostic, and - - PowerPoint PPT Presentation

Building Consortia for Enhanced Predictive, Diagnostic, and Therapeutic Care: The Example of the Biomarkers Consortium

Best Practices for Personalized Medicine Vancouver, BC March 9, 2011

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• The ultimate deliverable:translation of personalized medicine to the

clinic and patient

• Dr. Daniel Bednarik, Director, Genomics and Bioinformatics,

Cardiome Pharma

• Strategies and barriers to deliver personalization to the point of

care Dr Brad Popovich, Chief Scientific Officer, Genome BC

• ASK for confident decisions: harnessing the power of semantics
• Dr. Erich Gombocz, Vice-President and Chief Scientific Officer,

IO Informatics

Building Consortia for Enhanced Predictive, Diagnostic, and Therapeutic Care

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Increased Need for Public- Private Partnerships

Declining productivity in biopharma R&D → “externalization” of research Expansion of “pre- competitive” field Decline in government health research budgets

→ funding gap

Regulatory challenges → increasing complexity, limited budgets Escalating complexity of biomedical science and technologies Emergence of viable collaborative models → e.g., SNP Consortium, Gates Foundation

Conv

• nver

ergen ence of e of mul ultiple fac actor

• rs

has has l led ed to

• the em

he emer erge genc nce of

• f publ

public- pr private par partne nerships in n bi biom

• medi

edicine

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• Clin

Clinic ical Practice – Diagno agnose or

• r ident

dentify risk for

• r di

diseas ease – Strati tify fy p patients ts – Assess sev ever erity/di diseas ase pr progr

• gression
• n

– Predi edict pr prognos

• gnosis

– Gui uide de treat eatment – Assess res espon ponse t e to

• treat

eatment

• Drug

ug Dev evel elopm pment – Assess rol

• le

e of

• f dr

drug ug tar arge get in n di diseas ease pr proc

• ces

ess – Assess how how a a dr drug ug candi andida date int nter eracts with h a a tar arge get rec ecep eptor

• r, enz

enzyme, or

• r

pr prot

• tei

ein – Tox

• xicol
• logy

gy – PK, PD, dos dosing ng – In n clini nical dev devel elop

• pmen

ent, as asses essing w g whet hether her a a dr drug ug is saf afe e and and ef effec ective

• Drug

ug Qual ualification – Inf nform regul egulatory dec decision

• n-mak

aking ng

Biom

• mar

arker ers have m have many uses any uses

Personalization

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* Polanski and Anderson (2006). A List of Candidate Cancer Biomarkers for Targeted Proteomics. Biomarker Insights 2:1– 48

Out of 1,261 putative cancer protein or peptide biomarkers described in the literature*, only 9 are FDA approved as “tumor associated antigens”

• Fewer than 1 per year

have been approved by the FDA since 1998

• This high percentage of

un-validated biomarkers is generalizable to other diseases

• This “biomarker barrier” in

which candidate biomarkers have not been validated needs to be

• vercome

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Biomarker qualification: the value of collaboration

• Biomarkers require extensive testing and qualification for

practical use

– Multiple studies to ensure integrity, reproducibility of results

• Qualification is challenging, expensive, and time-consuming

– Can require large amounts of data: literature, observational studies, clinical trials

• Qualification is based on consensus among the scientific

community

– Deep understanding of and agreement on disease risk, natural history, outcomes

• Qualification is a pre-competitive activity
• Qualification is difficult to accomplish this in a single institutional

setting ➜ Requi uires es partner nershi hips ps and and a a strat ateg egic appr proac

• ach

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As a result, a number of PPPs in biomarker discovery and development have emerged in recent years Some examples:

• ADNI
• Critical Path Institute (PSTC, CAMD)
• Serious Adverse Events Consortium
• Innovative Medicines Initiative (Europe)
• PROOF Centre
• The Biomarkers Consortium

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Founda Foundation

• n f

for

• r NIH Over

erview

• Established by Congress in 1990; incorporated in 1996
• Supports the NIH mission
• Close relationships with NIH
• 501(c)(3) non-profit organization

– Raised over $560M since 1996 – 50+ projects

• Non-governmental

– Directly solicits contributions – Flexible donor relationships – Creates open, inclusive, objective governance mechanisms – Timely, effective grants/contracts/project management

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Goal

• als of
• f The B

The Biom

• mar

arkers Cons

• nsor
• rtium
• Facilitate the development and standardization of biomarkers using

new and existing technologies

• Help qualify these biomarkers for specific applications in

diagnosing disease, predicting therapeutic response, or improving clinical practice

• Generate information useful to inform regulatory decision-making
• Make consortium project results broadly available to the entire

scientific community

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Non

• n-Profit O

Organi nizat ation

• ns (

(34)

Academy of Molecular Imaging Advanced Medical Technology Association Alliance for Aging Research Alzheimer’s Association American Association for Cancer Research American College of Neuropsychopharmacology American Diabetes Association American Health Assistance Foundation American Society of Clinical Oncology American Society for Clinical Pharmacology and Therapeutics American Society for Therapeutic Radiology and Oncology Arthritis Foundation Association of Clinical Research Organizations Autism Speaks Avon Foundation Battelle Memorial Institute Biotechnology Industry Organization CHDI Foundation Cystic Fibrosis Foundation Therapeutics Federation of Clinical Immunology Societies The Hamner Institutes for Health Sciences The Immune Tolerance Institute, Inc. International Society of Biological Therapy of Cancer Juvenile Diabetes Research Foundation Kidney Cancer Association The Leukemia and Lymphoma Society Michael J. Fox Foundation for Parkinson’s Research Ontario Cancer Biomarker Network Osteoarthritis Research Society International Pharmaceutical Research and Manufacturers of America PROOF Centre of Excellence Radiological Society of North America Society for Nuclear Medicine University of Illinois

Fo For-Prof

• fit C

Compan panies ( (28)

Abbott Laboratories Amgen Amylin AstraZeneca Banyan Biomarkers BG Medicine Boehringer-Ingelheim Bristol-Myers Squibb Celgene Corporation Daiichi Sankyo Eisai, Inc. Genstruct, Inc. GlaxoSmithKline InfraReDx, Inc. Johnson & Johnson Eli Lilly and Company Merck and Co., Inc. Meso Scale Discovery Metabolon, Inc. NextGen Sciences Orasi Medical, Inc. Pfizer Inc.

• F. Hoffmann-La Roche

RareCyte, Inc. Scout Diagnostics Sepracor Takeda Pharmaceuticals XOMA, Ltd.

Cont

• ntribu

buting ng M Mem ember bers ( (62) 62)

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Govern ernance ance

Executive Committee

NIH / FDA / Industry / Foundation for NIH CMS / Public-Patient Representative Cancer Metabolic Disorders Inflammation & Immunity Project 1 Project 4 Project 2 Project 6 Neuroscience Project 3 Project 5 Steering Committees Project Teams

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FDA DA ShaAvhree Buckman, Office of Translational Science Jeffrey Shuren, Center for Devices and Radiological Health Janet Woodcock, Center for Drug Evaluation and Research Indus ndustry Stephen Eck, Eli Lilly & Co. Gary Herman, Merck & Co., Inc. Garry Neil, Johnson & Johnson Sara Radcliffe, BIO Found

• undation
• n for
• r NIH Boar
• ard

Steve Paul, ex-Eli Lilly & Co. Ellen Sigal, Friends of Cancer Research

The B e Biomar arker ers Consor nsortium um Executiv ive C Commit ittee

Chai hairman an Charles Sanders, Foundation for NIH NI NIH Thomas Insel, National Institute of Mental Health Douglas Lowy, National Cancer Institute James Battey, National Institute

• n Deafness and Other

Communication Disorders CM CMS Barry Straube Publ ublic Mem ember ber Mary Woolley, Research!America

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I ni tia l I d ea

• r

Co nc ep t App rov ed Proj ect Con cep t Pro ject Pla n Ap pro ved Pro jec t La un ch

EC/ SC, RFA/ RFP or External Subm ission Steering Com m ittee/ Project Team Executive Com m ittee ( and Funders) Project Team Steering Com m ittee

• Scientific m erit
• Pre-com petitive
• Feasibility
• Protocol
• Resources
• I ntellectual

property

• Data sharing

and distribution

• Tim elines and

m ilestones

• Budget
• Hum an subjects
• Privacy
• Legal review
• Final QA/ QC
• Funding
• Contracts
• Project

m anagem ent

1 2 3 4 5

Projec ect D Developm

• pment

ent Proces ess

I nitial funding scan FNI H initiates form al funding requests

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Ac Accompl plishm shment ents t to Date

• 11

11 launc aunche hed proj projects (1 (1 com compl pleted) – 1 1 com compl pleted proj project (A (Adi dipone ponectin); 4 4 proj projec ects will com compl plete e in n 2011 2011 – 3 3 new new proj projects i in n 2011 pi 2011 pipel peline (i (inf nfectious disease, ease, OA, A, atheroscl rosclerosi erosis) s)

• Trend

rending t tow

• war

ards m more

• re indus

ndustry- and F and FDA-based based subm submission

• ns, m

more

• re qual

qualification proj projects

• Incr

creased m eased membershi ship b p base/operat

• perations c
• ns core
• Inc

ncre reasingly seen seen as as a a model

• del publ

public-pri rivat ate e part partner ershi hip

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– Neoadj Neoadjuvan ant Setti Setting ng – Chemotherapy before surgery in a population with locally advanced breast cancer (LABC) – Accelerates knowledge turns from 5+ years to 1 year – Adapt Adaptive Tr e Trial ial Design Design – Learn rapidly which drugs work for which patients, and apply that knowledge to subsequent patients within the trial – Molecu

• lecular and

and Im Imaging Biom aging Biomar arker er Guidanc Guidance, e, and and qualif qualificat ation of n of new new biomark biomarker ers – Multi ultipl ple Dr Drugs ugs Tested Sim Tested Simulta ultaneo eous usly, r repr epresen esenti ting differ differen ent signal signaling pathway g pathways – Or Organi ganizat ationa nal Effici Efficienci cies

On Study

MRI MRI Blood

Surgery

Biopsy Blood MRI Biopsy Tissue Taxane +/–New Drug (12 weekly cycles) AC (4 cycles)

Probability of Randomizatio n to Tx Arm

Adapt for subsequent patients

I-SPY 2 is Design gned ed to Accel eler erat ate e the Clinical al Trial Proces ess

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I-SPY 2 2 Proje

• ject w

will ill allow allow f fas aster dev devel elopment of

• f bet

better er t tar arget geted t treat eatments for

• r br

breas east c canc ancer:

• Dramatically improve the success rate for Phase III trials,

from 25- 30% historically to as high as 85% , and target therapies to patients where the benefit is greatest

• Significantly reduce the time to identify the best

compounds and move them to approval

• Reduce the number of patients required in Phase III trials

tenfold (from thousands to hundreds of patients)

• Significantly cut the cost of late-phase drug development

(by reducing the time and number of patients required in trials)

• Test new, more efficient paradigms for drug evaluation

and approval in concert with FDA

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THE SAT E SATURDAY ESSA ESSAY | OC OCTOB OBER 2 2, , 2010 A Ne New w Rx Rx f for Medicine Fed up with slow drug trials, cancer patients and doctors are testing a fast track to personalized treatments. By y RO RON W N WINS NSLOW

When 37-year-old Kerry Landreth discovered a lump in her breast last April, she was told it would take three weeks to get a doctor's appointment to have it checked. "I don't do three weeks," she recalls

• saying. "How about today?"

By the end of the day, she had talked her way into a doctor's appointment, a mammogram and a biopsy to determine whether the suspicious lump was a tumor. A few days later came the diagnosis: stage 2 invasive ductal breast cancer, a particularly aggressive form of the disease. When a surgeon recommended a double mastectomy, she decided to consider other

• ptions.

Thank hank Y You

• u

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Def efini nition of

• f a

a Biom

• marke

arker

“A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes,

• r pharmacologic responses to a therapeutic

intervention”

(Biomarkers Definitions Working Group, “Biomarkers and surrogate

endpoints: Preferred definitions and conceptual framework,” Clinical Pharmacology & Therapeutics, 69 (3): 89-95 (March 2001).

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Proj

• jec

ects Launc nched hed/Com

• mpl

plet eted ed to Date (11) 1)

Project N t Name/C /Committe ttee Execut ution O

• n Objective

Status us

FDG DG-PET Lung and Lung and Ly Lymphoma Proje jects ( (Ca Cancer S SC) C) [2 pr 2 proj

• jects]

Build case for FDA incorporation of FDG-PET into outcome measures for lung cancer/lymphoma Launched 1-2Q/2007; five year projects I-SP SPY T Y TRIAL AL 2 2 (Cancer SC SC) A personalized medicine trial that promises to accelerate the pace of identifying effective novel agents for breast cancer; patients will be classified according to biomarker profiles and randomized to control therapy for up to 12 agents Approved for execution Q3 2009 (9/2009); press conference announcing launch in March 2010 Adiponec

• nectin P

n Project ( (Met etabol abolic Dis Disorders S SC) C) Determine whether adiponectin has utility as a predictive biomarker of glycemic control Compl plet eted p ed projec ect – publications released in June 2009 Ca Carotid id M MRI RI Re Reproducib ibili ility Projec ect ( (Met etabol abolic D Disorder ders S SC) Establish a standardized carotid MRI protocol and impact of site/platform on reproducibility Launched Q3 2008; 24 month project Sarcopeni

• penia C

a Consens ensus us S Summit (Met etabol abolic D Disorder ers S SC) Generate a consensus definition of sarcopenia (age-related decrease in skeletal muscle mass) to provide specific guidelines for diagnosis/better enable regulatory decisions First phase launched July 2009; two year project Ide dentification

• n and

and Val alida dation of

• f

Markers t tha hat P Predi edict Long Long-Ter Term Bet eta C a Cel ell Func Function and and Mas ass (Met etabol abolic D Disorder ers S SC) Methodologic studies of the Meal Tolerance and the Maximum Stimulation Tests to validate and extend published data, as a prerequisite for a clinical trial of diabetes progression. Launched January 2011

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Proj

• jec

ects Launc nched hed/Com

• mpl

plet eted ed to Date (11) 1) (cont

• ntinue

nued) d)

Project N t Name/C /Committe ttee Execut ution O

• n Objective

Status us

Alzhei heimer mer’s D Diseas ease T e Tar arget geted ed CSF Prot

• teomi

eomics P Proj

• jec

ect ( (Neur euros

• scienc

ence e SC SC) Qualify a multiplexed panel of known AD CSF-based biomarkers; examine Beta-Site APP Cleaving Enzyme levels in CSF; and qualify a mass spectroscopy panel using Alzheimer’s Disease Neuroimaging Initiative CSF samples. Launched in Q2 2010 Alzhei heimer mer’s D Diseas ease T e Tar arget geted ed Plas asma P ma Prot

• teomi

eomics P Proj

• jec

ect (Neur euros

• scienc

ence S e SC) Qualify a multiplexed panel of known AD plasma-based biomarkers using plasma samples from the Alzheimer’s Disease Neuroimaging Initiative Launched 12/2008; results anticipated by Q3 2010 PET R Radi adiol

• ligand

gand Proj

• jec

ect (Neur euros

• scienc

ence S e SC) Develop improved, more sensitive radioligands with higher binding to the peripheral benzodiazepine receptor Launched 3/2009; two year project Plac acebo D ebo Dat ata a Anal nalysis i in n Alzhei heimer mer’s Diseas ease/ e/Mi Mild C d Cogni

• gnitive I

e Impai mpairment ment (Neur euros

• scienc

ence S e SC) Combine placebo data from large industry clinical trials and analyze them to provide better measures of cognition and disease progression for use in future AD/MCI clinical trials Launched 12/2009; three year project

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Additional

• nal Projec

ects Appr prov

• ved/

ed/In n Devel elop

• pmen

ent (5)

Project Name/Committee Execution Objective Status

Clini nical S Stud udies t to

• Eval

alua uate and e and Qua ualify K Kidney dney S Saf afety B Biom

• markers

(Exec ecut utive C e Committee) ee) Will compare performance, initiate clinical qualification, and advance regulatory acceptance of new urinary biomarkers of acute drug-induced kidney injury. The Critical Path Institute’s Predictive Safety Testing Consortium has successfully qualified for regulatory use in pre-clinical studies a panel of 7 kidney safety biomarkers; this project would expand these findings to the clinical setting. $3.25M, 2 year project; approved in Q3 2010 (8/2010); working to

• btain remaining funding needed

to launch project Endpo ndpoints f for

• r C

Clini nical al Tr Trial als of

• f

Drug ugs f for

• r B

Bac acterial I Inf nfections and and Pneum umoni

• nia (

a (Exec ecut utive e Committee) ee) Identify and qualify efficacy endpoints for use in regulatory approval of new anti-bacterial drugs on the basis of non- inferiority clinical trials in acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP) Project concept approved by EC in June 2010; anticipate project plan presentation in Q1/Q2 2011 Osteoar eoarthr hritis B Biomar arker ers P Project (Immuni unity & & Inflam ammat ation

• n

Steer eering C ng Committee) ee) Validate biomarker-based metrics that would serve as putative efficacy end-points in therapeutic development of regimens slowing the progression of knee osteoarthritis by leveraging the unparalleled resources of the NIH Osteoarthritis Initiative Project plan presented to IISC in January 2011; anticipate request for Executive Committee approval in Q1/Q2 2011 Ather heros

• scler

eros

• sis C

Comput uter er Model deling I ng Initiat ative ( e (Met etabol abolic Dis Disorders S SC) C) Will aggregate data from existing industry clinical trials to develop a mathematical model of atherosclerosis that integrates and validates known biomarkers. Approved concept; securing funding commitments and exploring cost/scope reduction Functional

• nal I

Imagi aging B ng Biomar arker ers for P Pai ain n and and Anal nalge gesia (Neur uros

• scienc

ence S e SC) This project aims to develop imaging as a functional biomarker platform focusing on pain and analgesia. This project also hopes to define standards for the use of fMRI in drug discovery and development trials. Project plan approved by Executive Committee in February 2010; anticipate ceasing activities around this project due to lack of funding interest