World Companion Diagnostics Summit · World Companion Diagnostics Summit Pre-Conference Workshop B:Identifying and Implementing Best Practices from Companion Diagnostic Development

World Companion Diagnostics Summit

Pre-Conference Workshop B: Identifying and Implementing Best Practices from Companion Diagnostic Development Case Examples: From Candidate Selection to Commercial Success

30th November 2010

Michael Thomas Stocum, MSM

Personalized Medicine Partners

Edward Duncan Blair, PhD MBA

Integrated Medicines Ltd

Workshop Objectives

Upon completion of this workshop, attendees should be able to:

1. Identify key biomarker activities in drug/diagnostic co-development

2. Outline core processes at various stages of co-development of a companion diagnostic

3. Understand the challenges that biopharmaceutical and diagnostic companies face during co-development

4. Discover how to overcome these challenges when partnering within and between organisations

5. Cite examples that demonstrate the typical value propositions for companion products

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Disclaimer

The authors of this presentation do not make any representation with regard to their contribution (scientific, consultative or financial) to the cases presented, unless noted in the slides as presented. Further, any external third party (not developed by PMP/IML) material presented in these case studies is public, non-confidential material that was received with permission from the individuals cited. This information is shared with you for your individual use as a participant in this workshop and should not be duplicated in any way without the prior consent of the presenters of this workshop. The recipient is responsible for obtaining any necessary permissions to share or utilize any external third party material in this presentation.

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Workshop Outline

1. INTRODUCTION – 30mins

• Name, affiliation, your key roles, your key interests, an IL-KF

2. CASE STUDIES BASED ON STAGE OF PRODUCT DEVELOPMENT MOST IMPACTED – 2hrs

Four key cases plus others alluded to

3. CONCLUSIONS – 30 mins

Discussion of lessons learned and how best applied

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1. INTRODUCTION

6

About Your Facilitators

1. Michael T Stocum MSM – “Mike”

• Managing Director of Personalized Medicine Partners, LLC

• Positions in pharmaceuticals, including biologics, molecular diagnostics and biotech/ start-ups

• Past employers GlaxoSmithKline, Xanthon, Organon Teknika/Organon

• Qualified pilot and two-handed darts player

2. Edward D Blair PhD MBA – “Eddie”

Managing Director of Integrated Medicines Ltd

Chairman of Integrated Magnetic Systems Ltd (IMSL), NXD at IDS Holdings plc, visiting scholar at the Cambridge University.

• Past employment in pharmaceuticals (GSK) and biotech/ start-ups (Phynova, ITI)

• Unqualified pilot and partially successful mountaineer

Views Are Influenced By Cases…We have worked for an aggregate of 30+ years integrating biomarkers and tests (including novel laboratory developed tests and IVD kits) into therapeutic development and routine care settings

Working on HIV-1 viral load clinical applications in combination with novel therapeutics (NRTI, NNRTI & PI) in mid-late 1990s

Developing a novel “open source” HIV resistance RVA testing platform (in vivo ≡ in vitro) in late 1990’s

Co-leading project team that co-discovered correlation of HLA-B5701 and Hypersensitivity Reaction to Abacavir in early 2000’s

Comprehensive enabling programme (clinical trials, technology scouting, KOL management) on liver fibrosis and disease modification

Integrating novel biomarker tests (p-Her2, k-ras, etc.) on multiple platforms (genomic, IHC, etc.) into development of novel oncology therapeutics, such as lapatinib throughout 2000’s

Enhancing therapeutic development in additional disease areas such as cardiovascular, neurological, metabolic, respiratory and inflammatory

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1. INTRODUCTION TO COMPANION DIAGNOSTICS AND PERSONALIZED MEDICINE Background information

Context of case studies

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PATIENT-TARGETEDTHERAPIES

INNOVATIVEMEDICINES

THERAPEUTIC NEED

Right Medicine

Right Patient

Right Disease

Right Time

Right Dose

Right Response

Personalised Medicines

Right Price

Appropriate biomarkers and

Companion Diagnostics

10

Multiple Stakeholders – A Healthcare Value Net*

Government/ Regulators/ Payors

Direct healthcare providers

Industry –PharmaCo/ BiotechCo/ DxCo/ CRO

Patient (consumer/

beneficiary of healthcare)

*Brandenberger & Nalebuff, 1995

11

Safety, efficacy ….

Keys issues withmedicines today

are …..

*

*5th – 12th September 2005

and cost-effectiveness

12

Number of patients treated

All Selected Targeted

Pric

e of

med

icin

e

Low

Moderate

High

BLO

CK

-BU

STER

One

dru

g fit

s al

l; po

or re

spon

se

rate

s (2

0-80

%) &

risk

of

SA

Es

(>1%

)

SEG

MEN

T-B

UST

ERD

rug

resp

onse

s m

onito

red

for e

ffica

cy

and

SA

Es

usin

g di

agno

stic

-type

test

(C

Dx)

NIC

HE-

BU

STER

Dru

g gi

ven

to

spec

ific

patie

nts

dete

rmin

ed b

y pr

edic

tive

test

s (M

ol D

x; P

Gx)

Hi volume, low price

Low volume, hi price

Billion dollar sales line

Migration from block-buster treatments to high-value targeted treatments

*From Blair ED (2009) DDW 3:27, after Trusheim et al (2007) NRDD 6: 287

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PrognosticHow is the disease likely

to progress in the patient?

BiomarkerDiscovery – what biological parameters are changed?

Validation – are these changes reproducible?

SurrogateClinical - does the disease status

appear to be changing? PK/PD - does the lack of response reflect no

efficacy or poor pharmacology?

Companion Diagnostic (CDx)Does the patient

have a specific disease and will he/she respond to therapy?

The “test” continuum

Qualification

Commercialization

14

Timelines for Diagnostic and Medicine Co-Development

Concurrent FDAapproval

Discovery

Pre-clinicalPhase I

Phase II

Phase III

FDA Review

Project Initiation

8 years 15 years

Drug Development

Diagnostic Development Marker Discovery

Test DevelopmentRegulatory Review

Latest date to begin companion test programme

Candidate selection Commercial success

The Seven Stages of Highly Effective CDx Products and the Questions Each Answers…

1. Defining unmet need – what is the problem? - TPP

2. Biomarker discovery – what is available to solve the problem?

3. Technical assay validation – can you measure the biomarker(s)?

4. Clinical validation – is it present and relevant in the clinical condition/disease?

5. Clinical utility – does it provide actionable information about the condition/disease?

6. Medical utility – is the information used to make a treatment decision that improves an outcome (inclusion in treatment guidelines)?

7. Commercial adoption – is it established as standard of care and appropriately reimbursed (health/economic benefit)?

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Target Product Profile (TPP) Target Test Profile (TTP)

Indication (primary, further)Pharmacological ClassMechanism of ActionPresentation

o Route of administrationo Formulation

Core Claimso Primaryo Secondaries

Dosing RegimenSelling PriceCost of GoodsMarginGold Standard Treatments (current, future

competition)Reimbursement StatusPatent expiryEstimate Dates of Registration & Launch

Key business partnerMedicine supported by testMedicine development phase Test Value Proposition Intended use Epidemiology Risk evaluation (PoS, feasibility) Estimated date and route of registrationMilestones (ongoing assessment)Additional information

o QCo technology o gold standard o performance standards,o clinical sample & analyteo test locationo cost & pricingo IP

Medicinal Product and Companion Test Profiles Provide a Map Through the Seven Stages (summary)

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Impact of companion tests (CDx)*

Faster to market or Faster to

Decision

Time -years0 5 10

Sales

*Adapted from Gilham, 2002

Enhanced peak sales

Extended life cycle

Reduced time to peak sales

Product Differentiation More convincing clinical information Increased efficacy & tolerability Enhanced HE outcome Improved risk/benefit

Market Expansion Identification of at risk patients Diagnosis of new patients Novel disease indications Increased compliance

Expedited Drug Development Surrogate instead of clinical endpoints Better defined trial populations reduce enrollment Clearer scientific rationale speeds recruitment screening

Adding Value to a Drug’s Profile Through Biomarker Testing

For more information see: Baker, M., 2005 Nat Biot 23(3) 297-305

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CDx-guided Improvements in attrition?

Booth et al NRDD 2: 609 (2003) Walker & Newell NRDD 8: 16 (2009)

Factors underlying this difference are likely to include the targeted nature of kinase inhibitors and the improved design of clinical trials; for example, biomarker-driven patient stratification.

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CDx offers increased revenue through better commercialization?*

*Trusheim et al NRDD 6: 287 (2007) *Agarwal PharmExec.com (Jan, 2009)

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Financial impact of a Companion Diagnostic?*

No

Yes

Discounted Cash Flow - No Dx, NPV = $892 (15% dcf)

-1000

-500

0

500

1000

1500

2000

2500

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020

Year

Reve

nue

& Co

sts

Revenue Costs

Discounted Cash Flow - Companion Dx, NPV = $2,694 (10% dcf)

-1000

-500

0

500

1000

1500

2000

2500

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020

Reve

nue

& Co

sts

Year

Revenue Additional Revenue Costs Dx test

NPV uplift:$2694M

- $ 892M$1802M

*Blair ED, (2008)

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Impact of CDx co-development*

Davis et al (2009) Nature Rev Drug Disc 8: 279

~$200M

~$800M

~$1000M

~$2000M

(~$1800M)

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Realistic CDx Market Value?CDx Market Opportunity

1.89.0

90.0

1.15.4

54.0

1.57.2

72.0

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

100.0

Singleproduct

5products

pertherapy

area

Top 10therapy

area

USD

bill

ions

HighLowMid-Range

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An alternate market assessment*

*Allen et al (Oct 2009) The new science of

personalized medicine – see www.PWC.com

http://www.pwc.com/�

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An alternate market assessment*

*Allen et al (Oct 2009) The new science of

personalized medicine – see www.PWC.com

~$42bn

($54bn – $90bn)

http://www.pwc.com/�

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Apportioning value in a Dx-Rx deal?Diagnostics Partner Revenue & Costs

-500.00

0.00

500.00

1000.00

1500.00

2000.00

2500.00

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

2017

2018

2019

2020

Year

Rev

enue

& C

osts

Pharma Partner Revenues & Costs

-1000

-500

0

500

1000

1500

2000

2500

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020

Year

Reve

nues

& C

osts

Discounted Cash Flow - Companion Dx, NPV = $2,694 (10% dcf)

-1000

-500

0

500

1000

1500

2000

2500

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020

Reve

nue

& Co

sts

Year

Revenue Additional Revenue Costs Dx test

Dx NPV = $84 M ($0M)

Rx NPV = $2,610 M ($892M)

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Diagnostics Partner Influence (∝ Pharmaceutical Partner Urgency)

Lo Hi

Dia

gnos

tics

Part

ner

Rev

enue

s &

Ben

efit

Dire

ct &

Sca

le

Eco

nom

yIn

dire

ct &

Sco

pe

Eco

nom

y

TurnaroundOutcome: Product

Rescue1.8bn (90%R, 10% D)

Use-to-orderOutcome: Market

expansion$1.3bn (99%R, 1% D)

Make-to-orderOutcome: Market

penetration$1.9bn (98%R, 2%D)

IntegratedOutcome: Co-developed

test & medicine$1.8bn (97%R, 3%D)

PharmaCo-DxCo Relationships*

*Blair, Future Medicine 3/2010; PMC response to FDA, 12/2009

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Unmet needs by therapy area*

*Davis et al (2009) Nature Rev Drug Disc 8: 279

DiabetesAsthma

CNS Drugs

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2. CASE STUDIES

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Examples of Companion Diagnostics*

*M Allison NBT 26(5):509 (2008) Is Personalised Medicine finally arriving?

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Examples of Companion Diagnostics (cont)*

*Case for Personalised Medicine, 2nd Edition (2009), www.personalizedmedicinecoalition.org

http://www.personalizedmedicinecoalition.org/�

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Diagnostics Partner Influence(∝ Pharmaceutical Partner Urgency)

Lo Hi

Dia

gnos

tics

Part

ner

Rev

enue

s &

Ben

efits

Dire

ct &

Sca

le

Eco

nom

yIn

dire

ct &

Sco

pe

Eco

nom

y









SELECTED WORKSHOP CASE STUDIES


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Diagnostics Partner Influence(∝ Pharmaceutical Partner Urgency)

Lo Hi

Dia

gnos

tics

Part

ner

Rev

enue

s &

Ben

efits

Dire

ct &

Sca

le

Eco

nom

yIn

dire

ct &

Sco

pe

Eco

nom

y









SELECTED WORKSHOP CASE STUDIES


1. Pfizer maraviroc

and

Monogram trofile test

2. Amgen panitumumab

and

KRAS test

4. AZ/ Prom budesonide

and

Prometheus Serology 7 test

3. GSK abacavir

and

HLA SNP test

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2. CASE STUDIES

Development – Pfizer & Monogram for Selzentry & Trofile - EB

Regulation – Amgen, Imclone & DxS – Vectibix, Erbitux & KRAS – MS (additional details see S. Little presentation at 3:45 PM, 1-Dec)

Commercial rescue – GSK/ HLA SNP – Abacavir sales returned – MS (additional details see A. Hughes presentation at 3:30 PM, 2-Dec)

Product line extension – AZ/ Prometheus – protection of budesonide from generics – EB/ ALL

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Case Study 1 – Pfizer-Monogram

Pfizer Celsentri (maraviroc) and Monogram Biosciences Trofile test (2004? - Present)

• Test used in maraviroc clinical development

• FDA approval of drug 6 August 2007 drives demand for test

• Income up-lift direct to Monogram

Only one CCR5 inhibitor developed, so Pfizer (VIIV) and Monogram relationship monogamous

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HIV – the cradle of modern personalised medicine

Control groupGenotype group

Weeks of Regimen

12(p = 0.01)

24(p = 0.05)

Red

uctio

n in

HIV

-1 R

NA

0-1.40

-1.20

-1.00

-0.80

-0.60

-0.40

-0.20

0

VIRADAPT (Durant et al, 1999)

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Why testing matters

• High baseline viral load may be a surrogate for amounts of virus resistant to agents in the backbone that are large enough to cause treatment failure in any ARV regimen

• Amount of CXCR4-using virus was significantly predictive of response to MVC + CBV

• As with all HIV antiviral combination therapy, the probability of success with a combination regimen is increased with potent regimens and/ or regimens that have a high resistance barrier

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HIV lifecycle

39

HIV Tropism, gp120 and co-receptors

40

MVC Clinical Studies – Motivate-1 and -2, Merit

41

Maraviroc mode-of-action

42

Maraviroc-Trofile Co-development Timelines

FDA Approval 6AUG07

DiscoveryMIP/ CCR5

Pre-clinicalPhase I

Phase II

Phase III

FDA Review

1996 2002 2009

Maraviroc development

Trofile test development

Assay Technology(SFO labs, 1995)

Test DevelopmentRegulatory Review

Companion test programme initiated (2H2000)

Co

mm

erci

al s

ucc

ess

Dec

emb

er 2

00

9

CLIA accreditation

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Maraviroc monograph (Pfizer/ VIIV)

“CCR5 tropism should be confirmed using a highly sensitive tropism assay prior to initiation of CELSENTRI therapy.

Outgrowth of pre-existing low-level CXCR4+ or dual/ mixed-tropic HIV-1, not detected by tropism testing at screening, has been associated with virologic failure on Celsentri.”

Why is this important to Pfizer/ VIIV?

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Virological failure – out-growth vs resistance

45

The fear of resistance without Plan B

46

Trofile Test v1

47

Trofile Test v1

48

Trofile Test v1 (lay)

49

Trofile Test v2

100% Sensitive at detecting 0.3% CXR4-using minor variant

Uses the complete gp160 coding region of the HIV-1 envelope protein to ensure that all determinants of tropism are tested

Successful amplification and reliable results with viral load ≥1,000 copies/mL

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Trofile ESTA improves selection and outcome*

*Basis of FDA expanded use approval 20Nov09

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Trofile v1 and ESTA (v2) vs Quest HDA

CONCLUSIONS

•The concordance between CE-HDA and Trofile or TF-ES was approximately 70%.

•The agreement beyond chance between these tests (kappa statistic) was modest.

• Comparing groups with discordant tropism results, CE-HDA did not achieve non-inferiority to TF or TF-ES, and this assay appeared inferior to TF-ES

• Re-calibrating the heteroduplex assay cut-offs using 454 testing as a gold standard slightly improved the concordance with TFES, but did not appreciably change the virologic outcomes.

• TF-ES tropism results provided the best prediction of having <50 copies/mL 24 weeks post-MVC and detection of X4 post-MVC.

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Trofile ESTA vs Sequencing

Maraviroc Genotyping by Ultra-Deep Sequencing ultrassensitive 454 Test: 16% discordance compared with original Trofile assay; also, "suggesting that the percent of non-R5 virus is more important than the absolute non-R5 VL“,

i.e., for Trofile calls, the percent of non-R5 virus is more important than the absolute non-R5 VL

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Case Study 1 – Conclusions and Questions

Test essential for clinical development and marketing success

• Who paid for what and why?

Improved test crucial to separating out-growth of pre-existing virus from resistance

• Who drove upgrade and why?

Only one CCR5 inhibitor developed, so Pfizer (VIIV) and Monogram relationship monogamous

• How soon before partnership folds and why?

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Case Study 2 – EGFR-Ligand Dependent Signalling Inhibition by mAb and KRAS testImclone/BMS/MerckSerono, Amgen and Kras tests (1H09)

• Support for use of several tests in clinical development of cetuximab (ERBITUX) and panitumumab (VECTIBIX)

• Representations to EU regulators re: Vectibix and later Erbitux labelling

• US FDA positions

• Ensuring reimbursement through NICE for tests at full cost

Slide courtesy of S Patterson

EGF Receptor Signaling Cascade and the RAS-RAF-MAP Kinase Pathway

Activation by ligand



Receptor blockade by antibody



Receptor blockade by antibody

KRAS mutant

activation



Panitumumab (Vectibix®)US Package Insert

INDICATIONS AND USAGE• Vectibix is an epidermal growth factor receptor antagonist indicated as a

single agent for the treatment of metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy regimens. Approval is based on progression free survival; no data demonstrate an improvement in disease-related symptoms or increased survival with Vectibix. (1)

• Retrospective subset analyses of metastatic colorectal cancer trials have not shown a treatment benefit for Vectibix in patients whose tumors had KRAS mutations in codon 12 or 13. Use of Vectibix is not recommended for the treatment of colorectal cancer with these mutations. (1, 12.1, 14)

EGF Receptor Testing • Detection of EGFR protein expression is necessary for selection of patients

appropriate for Vectibix therapy because these are the only patients studied and for whom benefit has been shown [see Indications and Usage (1) and Clinical Studies (14)]. Patients with colorectal cancer enrolled in Study 1 were required to have immunohistochemical evidence of EGFR expression using the Dako EGFR pharmDx® test kit.

Adapted from Amado, et al. J Clin Onc 2008; 26(10): 1626-1634

Increased PFS Observed in Patients with KRAS Wild-type Tumors

KRAS Data and the Practice of Medicine Resulted in a Class Label Change

mCRC, metastatic colorectal cancer; SAP, statistical analysis plan

2007 Jan

2008 Jan

US Approval

SAP

KRAS

20020408

20020408 KRAS

ANALYSIS

2009 Jan

EU Approval

NCCN Practice Guidelines mCRC (28 Oct 08)

ODAC (16 Dec 08)

2010 Jan

ASCO PCO mCRC (13 Jan 09)

USPI change

CAP POET-KRAS/CRC (5 Nov 08)

20030181 & 20030203 WT-

KRAS RESULTS @ ECCO/ESMO

POOLED KRAS

ANALYSIS

Multiple studies

ASCO 2008



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What is the “Return on Investment?”

For panitumumab (Vectibix®):

• In 2009, annual global sales of $233M

• Estimated that approximately one third of these sales are from the EU or $75M which are the result of a k-ras test availability

• Estimated costs of the clinical testing <$20M

• Remainder of story still to be written

Eli Lilly recognized $390.8 million in revenue from U.S. sales of Erbitux in mCRC and head and neck cancer during 2009. Outside the U.S. in 2009, sales of Erbitux increased 23% to €697 million (about $910.6 million), according to Merck KGa. Sales of Vectibix in mCRC totaled $233 million in 2009 versus $153 million in 2008; Vectibix makes up roughly 6% of Amgen’s sales revenue. GEN 27-Sep-2010

http://www.genengnews.com/analysis-and-insight/amgen-s-biomarker-research-underlies-vectibix-success/77899340/

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Test essential for registration and reimbursement in the EU

• Who paid for what and why?

The test ultimately impacted the labelling of competing products and the label in other countries

• Who drove the label change and why?

The availability of a diagnostic also led to a change in medical practice

• How did the change in medical practice evolve, what drove the evolution and which came first, guidelines or labelling?

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Case Study 3 – Abacavir Commercial Position Improvement (“Rescue”)

• Abacavir had a serious adverse event in a small, but significant number of patients

• Emerging anti-retrovirals (tenofovir) were a significant commercial threat to abacavir

• Improving the safety profile was hypothesized to drive greater physician comfort with using the medicine

• GSK HIV franchise plans to include abacavir in multiple combination regimens, SAE put a number of the portfolio products “at risk”

66

Landmark SNP Study in Pharma

• Objective: Product differentiation by improving safety profile− Hypersensitivity reaction to

abacavir (nucleoside analogue)• Two phase study – candidate

genes and genome wide SNPs− 114 markers including HLA-A, -B

and -DR• Methodology: DNA Sequencing of Cases and Controls

− Matched for race, age, gender, CD4+ counts, treatment status, tolerated abacavir > 6 weeks

• Number of subjects chosen to allow detection of a difference in frequency of 15−20% (80% power)− goal 100 cases, 200 controls, matched 1:2

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• Data did not support changing the clinical assessment or management of HSR to ABC

• Proof of principle: pharmacogenetics plays a role in patient response to medicines

• Independent Academic confirmation2

Results1:• HLA B57+ plus other SNPs

are associated with HSR• High false negative rates

did not accurately predict individuals who will develop an HSR

SNPs for Product Differentiation –Adverse Event Avoidance

1 S. Hetherington, A. Hughes, M. Mosteller, D. Shortino, K. Baker, W. Spreen, E. Lai, K. Davies, A. Handley, D. Dow, M. Fling, M. Stocum, C. Bowman, L. Thurmond and A. Roses Genetic variations in HLA-B region and hypersensitivity reactions to abacavir The Lancet 359: 1121-1122, 2002

Cases(n=84)

Controls(n=113)

p-value

HLA-B57Present

39 (46%) 4 (4%) <0.0001

HLA-B57Absent

45 (54%) 109 (96%)

UPDATE: Confirmed HSR cases nearly eliminated in any study since that has used HLA B57+ as an exclusionary criteria!

2 Independent confirmation: Mallal, et al. The Lancet 359: 727-732, 2002

68 68

Performance Characteristics ofHLA-B*5701 Screening for ABC HSR

(PREDICT-1 Study)

HSRNo HSR

Pos Neg

Immunologically Confirmed HSR1

HLA-B*5701

23 025 794

Pos PV

48%

Neg PV100%

Sens 100%Spec 97%

Clinically Suspected HSR1 HLA-B*5701

Pos Neg

30 3619 762

Pos PV Neg PV

62% 96%

Sens 46%Spec 98%

1 Control Arm (Standard of Care) Data Only

Mallal et al; N Engl J Med 2008; 358(6):568-579

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HSR to Abacavir Test –Revenue Impact for HIV Franchise

2009 Sales 4Q % change

2009 % change

Epzicom/Kivexa (abacavir + lamivudine)

149 11 546 8

Combivir (zidovudine + lamivudine)

109 -5 425 -13

Trizivir (abacavir + lamivudine + zidovudine)

49 -19 201 -17

Zeffix (lamivudine) 55 N/A 217 -1Agenerase/Lexiva (fosamprenavir calcium)

44 -9 178 -4

Epivir (lamivudine) 30 -17 129 -19Ziagen (abacavir) 27 -7 105 -13

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What is the “Return on Investment?”

For abacavir (API in multiple products):

• Nearly 50% of the products in a $1.8B franchise contain ABC

• Most of franchise is in decline (competitive pressures/patent expiry)

• Novel abacavir combination with lamivudine is driving new growth, enabled by testing that essentially eliminated a troublesome adverse event (8% growth and >$0.5B in revenue)

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Use of HLA B57-01 Lab Developed Test all but eliminates HSR to abacavir

• Who drove the testing and why?

The test ultimately impacted the labelling of the product

• Who drove the label change and why?

The availability of a diagnostic also led to a change in medical practice

• How did the change in medical practice evolve enhance treatment options for HIV patients?

72

Case Study 4 – Budesonide and Serology 7In some scenarios, a test can be used to reposition a late-in-life cycle drug vs. (generic) competition

*Agarwal PharmExec.com (Jan, 2009)

73

Breakout Groups

Name Role Affiliation Sector

Bernhard Fritz-Zieroth Global Project Leader Bayer Shering AG Rx

Barry Michael Rx

Thomas Gilbert Associate Director Biogen Idec Rx

Jill Bourdage PPM Eli Lilly & Co Rx

Daniel Bollag Sr. V.P. Regulatory Affairs & Quality Ariad Pharmaceuticals Inc Rx

Mark Miglarese Vice President OSI Pharmaceuticals, Inc Rx


Arlene Hughes Genetics research & regulatory GSK Rx

Keith Wharton Principal Scientist Biogen Idec Rx

Thomas McElroy Director LifeTech Dx

Jeff Fill Director, Clinical Biomarker Lab Eli Lilly & Co Rx

Devon Campbell Head, Systems & Engineering Novartis Rx

Anton Gilbert Compound leader Biogen Idec Rx


Leia Smith Senior Principal Scientist Seattle Genetics Dx

Chandra Ramanathan Director Bayer HealthCare Phamaceuticals Rx

Lianne McLean Senior Director Myraqa, Inc. Dx

Crane Harris Director, Business Development Illumina Dx

Mark Curren Biomarker group Centocor Rx

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Your task

Discuss question (20’) and report back (3x10’)

Group 1 (Rx perspective)

• How would you use a CDx to reposition a late cycle medicine?

Group 2 (Rx perspective)

• How would you use a CDx to line-extend a late cycle medicine?

Group 3 (Dx perspective)

• How would you position a CDx to support a late cycle medicine?

75

Other benchmark cases - 1

Merck (MSD) relationship with Celera on cancer biomarkers and companion tests may involve pharma royalty payments to DxCo

76

Other benchmark cases - 2

Health Technology Assessment* (cf UK NICE)

Andrew Dillon, Chief Executive of Nice commented ….”the NHS will only pay for the drug when it has been proven to work…”

To implement this risk-sharing agreement, clinicians are required to measure the levels of serum M protein (SMP; a specific biomarker for tumour load) after a maximum of four cycles of treatment. If the patient has a reduction in SMP of 50% or more, indicating a complete or partial response, treatment will continue and the NHS will pay. If not, the JnJ must rebate the full cost.Hughes NRDD 6: 945 (2007)

*Hughes NRDD 8: 261 (2009)

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3. CONCLUSIONS

Lessons learned and how to apply going forward

Changing environment driven by “open innovation”, i.e., pre-competitive research

Your views, experiences, comments

78

Mike Stocum

[email protected]

&

Eddie Blair

[email protected]

Thank you and.…

….Any questions?

Documents

World Companion Diagnostics Summit · World Companion Diagnostics Summit Pre-Conference Workshop B:Identifying and Implementing Best Practices from Companion Diagnostic Development