Gauging the market for new diagnostic tests for bloodstream and respiratory tract infections

Ellen Jo Baron, Ph.D., D(ABMM)Director of Medical Affairs, CepheidProfessor Emerita, Pathology, Stanford University

With advice from:Fred Tenover, Ph.D., D(ABMM)Exec. Director of Scientific Affairs, Cepheid

Peter BetzelosVice President, Marketing

© Cepheid – Proprietary & Confidential

No longer an Oxymoron: Rapid Diagnostic MicrobiologyKey Decision Points – Diagnostic Lab

Stanford Clinical Laboratory

Lab-based decision factorsWhy introduce a new test?

1. Medical need (physician requests)

2. Enhanced clinical value (decreased TAT, more consistent, more sensitive, more accurate results)

3. Volume of orders drives bringing sendout test in-house

Virology Lab 7Virology Lab 7--month Test Volume and Instruments Usedmonth Test Volume and Instruments UsedHIV Seq (QiaSymphony; AmpliTaq; ABI 7400)

HCV Seq (QiaSymphony; LightCycler; ABI 7400)

HPV Hybrid Capture: Digene

HCV PCR (Ampliprep; AmpliTaq)

HSV PCR (EZ1; LightCycler)

HIV PCR (Ampliprep; AmpliTaq)

HBV PCR ( Ampliprep; AmpliTaq)

Flu & RSV PCRs (EZ Cube; RotorGene)

EBV PCR (Qiagen M48; LightCycler)

CMV PCR (MagnaPure; Cobas)

Chlamydia/GC SDA (BD Viper)

Lab-based decision factorsOn introducing a new test

4. Ease of performance vs lab personnel skillspersonnel skills

5. Ability to test more sample types6 Physical requirements: drains6. Physical requirements: drains,

electrical, space 7 V lid ti i t7. Validation requirements8. Cost; return on investment

GeneXpert® in place in Stanford Core Lab

Corporate decision factorsOn developing a new testOn developing a new test

1. Market opportunitypp ya. Total market; product valueb. Growth rates: flat vs growthc. Projected manufacturer market share

2. Competitive offeringU i d t t h la. Unique product or technology

b. Desirability vs other similar products3 Strategic corporate alignment3. Strategic corporate alignment

a. Menu expansionb. Portfolio or program offeringb. Portfolio or program offeringc. “Panel” test requirements

Worldwide Molecular Diagnostics Market(from Kalorama Information report)(from Kalorama Information report)

$ Millions$ Millions

Unique Ability to Meet Diverse Testing NeedsPlatform consolidation = market opportunity

WOMEN’S HEALTH

CRITICAL INFECTIOUS

DISEASE

HEALTHCARE ASSOCIATED INFECTIONS

IMMUNO-COMPROMISED ONCOLOGY GENETICS

Roche

GenProbe

Qiagen

BDBD

Abbott

Each color denotes separate platform.

Strategic Market DevelopmentStrategic Market Development

REFERENCE LABS HOSPITALS ALTERNATE SITES

RETAILPHYSICIAN LONGCORE LAB

RETAIL PHARMACY/ URGENT

CARE

SURGERY CENTERS

OFFICE LABS

(GPs,Urology,OB/GYN)

LONG TERM

HEALTH CARE

REFERENCE LAB

DISSEMINATED (ICU, ED, Admissions,

L&D, STAT)

Competitor Product Applicability

Competitor Product Applicability

Competitor Product Applicability

Applicability

Each color denotes separate platform.

Market growth by segment(f K l I f ti t)(from Kalorama Information report)

Bloodstream and respiratorBloodstream and respiratory tract infections fit here

US IVD Xpert Test Portfolio: NowWomen’s

Health

HealthcareAssociated Infections

Critical Infectious Disease

CLIA-Waived Testing

Oncology & Genetics

Virology

GBSMRSA/SA BC

SA Nasal

vanAfor VRE

MRSA/

Flu HemosILFII & FVEV

SA Nasal Complete

MRSA/SA

SSTI

MRSA C. difficile

• 11 Tests Available in US• Active Projects

– US Market: SA (CW), MDR-Tuberculosis, BCR/ABL

C. diff/Epi

( ), ,– World Markets: CT/NG, HIV, HPV, HCV

Bloodstream and respiratorBl d t d i tBloodstream and respiratory tract infections fit here

Bloodstream and respiratory tract infections fit here

Corporate decision factorsOn developing a new testOn developing a new test

4. Legal and net margin4. Legal and net margina. Intellectual productb. Patent protection (when

i )expires)c. Royalties

5. Feasibility of successful yproduct development

a. Production, developmentb M f t i ( tb. Manufacturing (costs,

margin)6. Reimbursement issues

Should Cepheid develop a yeast cartridge for positive blood cultures?cartridge for positive blood cultures? 1 aspect: Meta-analysis of literature

13 total articles met expanded criteria (first they required data):

1. EORT/MSG criteria used as gold standard

2 Blood cultures performed2. Blood cultures performed3. Sens & Spec of beta-glucan for

candidemia could be determined from 5 publications

4. Sens & Spec for invasive fungal disease ld b d t i d f 10 bli ticould be determined for 10 publications

Beta-glucan Results Summary

Number of pts evaluated ranged from 40 to 871 (13 studies evaluable) Ai t i

Proven/probable patients 111 (range 3-72)

(13 studies evaluable) Air crescent sign

Sensitivity/pt for >80 pg/mL 74% (42-100%) (10 evaluable)

Specificity/pt 89% (81 98%) (8 evaluable)Specificity/pt 89% (81-98%) (8 evaluable)

Proven/probable/possible pts 645 (range 11-209)

Sensitivity/pt for >80 pg/mL ~72% (62-86%) (7 evaluable)

Specificity/pt 89% (76-96%) (5 evaluable)

Candidemia Results Summary

Number of pts evaluated ranged from 40 to 871ranged from 40 to 871(5 ß-Glucan studies evaluable)

Culture pos patients 732 (range 6-163)

Sens > 80 pg/mL 81% (range 57-100%)

Spec > 80 pg/mL 63% 4 studies (range 44-84%)(range 44 84%)

Summary Points

1. Blood cultures detect most agents of septicemia, not just yeast

1 Bl d lt d X t C did b th d t t1. Blood cultures and Xpert Candida both detect Candida in only 14% of invasive candidiasis

2. Xpert Yeast will NOT provide advantage vs. Blood2. Xpert Yeast will NOT provide advantage vs. Blood culture except occasional earlier result

3. ß-D-glucan ~81% sensitive for Candidemia4. New methods will allow broad adoption of ß-D-

glucan test, which will be ordered first (false assumption)assumption)

5. Xpert Candida would be used as confirmatory test only, and perhaps not at all

6. Successful competitor: AdvanDx Yeast StopLight

Septicemia Dx: SeptiFast (Roche)

(45)

(32)

(45)

(32)

Yanagihara et al. Critical Care 2010, 14:R159

Cepheid’s first foray into sepsis 2004-2009

Collaboration between bioMerieux and Cepheid to develop septicemia cartridge begins

Collaboration with Cepheid ends

Bact IDBact ID

? Commercially viable

New Test Decisions based on Unforeseen Circumstances

7. Corporate responsibility

Unforeseen Circumstancesp p y

8. External incentives

MDRO ProjectMDRO ProjectMDRO

• Growing global need to identify multi-drug• Growing global need to identify multi-drug resistant organisms, especially carbapenem-resistant strains

• Partnered with Dr. Lance Peterson to develop NIH grant on rapid detection of MDROs

• NIH Award leads to collaboration on development of MDRO cartridge (indevelopment of MDRO cartridge (in progress)

Direct Detection of Carbapenem Resistance Genes from Rectal Swabs by Multiplex PCR (one swab from U.S.)y p ( )

VIM

KPC

Control

Assay completed in approximately 1 hour including sample preparation, amplification, and detection. Both resistance genes (KPC and VIM) confirmed

by PCR on isolated colonies

2016 US IVD Xpert Proposed Test Portfolio

Women’s Health

HealthcareAssociated Infections

Critical Infectious Disease

CLIA-Waived Testing

Oncology & Genetics

Virology

BCR/ABLMonitor

V2EV Flu HIV

QuantHCV

QuantMRSA/SA BC

SA N l

vanAfor VRE

MRSA/ G t B

GBS CT/NG

BCR/ABL

HemosILFII & FV

Breast

SA

CT/NG

Flu A/B Panel

MRSA/SA HBVMTB/RIFSA Nasal Complete

MRSA/SA

SSTI

MRSA C. difficile

Gastro B Panel Vaginosis Vaginitis

HPV

BCR/ABLMONITOR

V1

Bladder Cancer Monitor

Breast CA RXStrat

Breast Cancer

MetastasisRisk

CT/NG MRSA/SA SSTI HBV

Quant

Group A Strep

Vaginitis Group AStrepRSV

HSV TypingLesion

C. diff/Epi Norovirus

MDRO VAP MRSA/SA

Vaginitis/Vaginosis

MRSA/SA

VAP Gram Negative