The Pipeline for New HIV Diagnostics: The Promise and the Challenges

Maurine M. MurtaghWHO-UNITAID Co-Hosted Satellite Event

AIDS 2012, XIX International AIDS ConferenceWashington, DC

July 22, 2012

There are several other promising platforms on the horizon. These include the Daktari, mBio and BD platforms as well as disposables from Zyomyx and Omega Diagnostics.

There are already several POC CD4 platforms on the market and more are comingHumaCount CD4 NOW (formerly PointCare NOW), the Partec mini-CyFlow and the Alere Pima CD4 Test are already on the market.

The Alere Pima CD4 Test has been on the market since November 2009. In 2010, about ~650 devices were placed and ~580k tests sold; in 2011, this increased to ~1650 devices and ~900k – 1m tests sold; in 2012 through June, 750 analyzers have been placed, and 740k tests sold.

CD4 Product Pipeline*

2009 2010 2011 2012 2013

HumaCount

Partec Mini

Alere Pima CD4

Daktari

Omega Diagnostics

mBio

Zyomyx

Instruments Disposable

*Estimated - timeline and sequence may change

BD

2014

Monitoring HIV Patients – Device- based POC CD4

Company PointCare/Human Partec Alere Daktari

Platform Name HumaCount CD4 NOW

Partec CyFlow® mini POC

Alere Pima CD4 Test Daktari™ CD4 Counter

Type Desk top; ~26 lbs Bench top portable; ~11 lbs

Bench top portable; ~5.5 lbs

Bench top portable; ~5.5 lbs

Output Absolute & %CD4, WBC, Hb, total lymphocytes

Absolute & %CD4, WBC, total lymphocytes

Absolute CD4 Absolute CD4

Specimen Type 40 µL venous blood 20 µL venous blood 16 µL fingerstick blood 16 µL fingerstick blood

Cost/test ~$10.00 per test, including controls

~$3.96 per test; high volume discounts

$6.00 - $12.00 ~$8.00 per test; lower with volume discounts

Number of samples/run

~40 – 50 samples per day; TAT 8 minutes; no batching

Up to 250 tests/day; TAT 40 – 70 seconds per test after 15 minutes incubation

Maximum of ~20 samples per day; TAT 18 – 20 minutes per test

~40 – 50 samples per day; TAT 8 minutes; no batching

Equipment Cost ($US)

~$25,000 ~$9,380; point-of-care package at lower effective cost

$6,500 to $12,000 ~$1,000

Monitoring HIV Patients – Device-based and Disposable POC CD4

Company MBio BD Zyomyx Omega Diagnostics/Burnet

Platform Name Mbio CD4 System BD Point of Care CD4 System

Zyomyx CD4 Counter Omega Diagnostics CD4 Counter

Type Bench top portable; ~6.6 lbs

Bench top; ~11 lbs Disposable cartridge with mechanical mixer/spinner (less than 11 lbs)

Disposable cartridge with reader (~14 ounces)

Output Absolute CD4 Absolute CD4, %CD4 & Hb

Absolute CD4 Absolute CD4

Specimen Type 10 µL fingerstick blood

16 µL fingerstick blood

100 µL fingerstick blood 40 µL fingerstick blood

Cost/test TBD TBD <$8.00 per test $2.00 per test estimated

Number of samples/run

~100 samples per day; TAT 20 minutes (17 minutes in cartridge; 3 minutes instrument reading)

Maximum of ~25 - 30 samples per day; TAT 2- 5 minutes plus 20 minutes of incubation

~40 samples per day; TAT 10 minutes; batch processing TBD

~120 samples per day; TAT ~40 minutes, including incubation

Equipment Cost ($US)

TBD TBD ~$200 for mixer/spinner; may be included in cost per test with TBD volume of test cartridges

~1,200 for reader, expected to go to $400

One of these, the viral load assay for the Liat platform, may still launch in late 2012.

Additional platforms will follow over the next few years.

New Options for Viral Load Monitoring and EID are also on the Horizon

A number of new Viral Load/EID POC diagnostics are in development.

These will have lower instrument and per-test costs, but will also have lower throughput than lab-based systems.

Technology Pipeline – Viral Load and EID*

2012 2013 2014 2015 2016

Alere Q

NWGHF VL

Lynx EIDSAMBA EID SAMBA VL

Liat

WAVE 80 EOSCAPE

Gene XPert

Micronics

Biohelix

ALL

Cavidi AMP

Lumora

Monitoring HIV Patients on ART – Device-based Viral Load/EIDCompany IQuum Alere WAVE80 DRW NWGHF

Platform Name

Liat™ Analyzer Alere Q WAVE80 EOSCAPE-HIV™ System

SAMBA Analyzer Lynx

Type Bench top portable; ~8.3 lbs

Bench top portable; <11 lbs

Bench top portable analyzer with separate processing units

TBD Bench top portable processor unit with cartridge

Output Quantitative or qualitative VL

Quantitative HIV-1 RNA

HIV-1 RNA Semi-quantitative VL or Qualitative for EID

P24 antigen assay for EID

Specimen Type

200 µL plasma or 10 - 50 µL fingerstick blood

25 µL fingerstick or 25 µL heel stick

100 µL fingerstick blood 200 µL plasma (VL) or 100 µL whole blood (EID)

~80 µL blood from infant’s heel

Cost/test TBD TBD <$20 per test TBD ~$7.00 to $15.00 per test

Number of samples/run

~8 - 15 samples per day depending on LOD; TAT 30 - 55 minutes, no batching

Max of ~10 samples per day; TAT 30 – 60 minutes

~50 samples per day with 6-8 processing units and a single analyzer; TAT 50 minutes; random access

4 samples per run; TAT ~90 to 120 minutes depending on assay

~16 samples per day; TAT 30 minutes (plus 10 minutes for blood draw and sample prep)

Equipment Cost ($US)

~$25,000, may be lower in LRS

TBD ~$10,000 for one analyzer with 2 processing units

TBD ~$400 - $700

What does it take for POC diagnostic technologies to be “game changers”?

There are some very promising POC diagnostics in the pipeline. In order for them to be “game changers”, they will need to help compensate for diagnostic system weaknesses in resource-limited settings:

• Human Resources: Lack of trained staff, high turnover and insufficient training opportunities

• Supply Chain: Ensuring the efficient and reliable supply of essential diagnostic products throughout the laboratory system is a significant obstacle to diagnostic delivery. Long and difficult transport of test reagents and consumables are the norm often under extreme temperature conditions, including temperature spikes.

• Service/Maintenance: Lack of diagnostic equipment and frequent and prolonged breakdowns of equipment (lasting months and sometimes years)

• Diagnostic Errors: Studies have shown that even for simple tests, quality-controlled and reproducible testing remains a major challenge in resource-limited settings; test errors are observed frequently.

Priority Characteristics of POC Diagnostics

In addition to strong technical performance and cost effectiveness, in-country research has demonstrated the following high priority characteristics for POC diagnostics:

• Durability: device with no electronic or mechanical maintenance beyond simple tasks; rugged device that will tolerate high temperature tolerances and will tolerate shock and vibration; cartridges with long shelf life and ability to survive extreme temperature fluctuations and humidity; no cold chain or clean water required; battery back-up

• Ease of use: simple sample preparation (few operator steps); ability to use unprocessed sample specimens; no operator intervention required during analysis; self-contained kits; little operator calibration; simple user interface and read-out

• Training: test simple enough that its use can be explained to a healthcare worker in a day’s training or less; test simple enough to permit informal training among healthcare workers

• Self-contained Quality Control: if device-based, device designed to cover a large number of quality issues rather than leaving them to staff: e.g., detecting expired kits (reject); detecting inadequate sample volume (reject); running process control

The Limitations of POC Testing

POC testing has the promise to fill gaps in access and capacity, and there are some exciting POC diagnostics either here or coming over the next few years. But, there is no silver bullet technology yet.

Understanding the realistic value and preparing for the implementation challenges is imperative to increase access to the right populations in the right way.

Acknowledgments

UNITAID

The Bill & Melinda Gates Foundation

Dr. Trevor Francis Peter

Advanced Liquid Logic, Alere, BD Biosciences, Biohelix, Burnet/Omega Diagnostics, Cavidi, Cepheid, Daktari Diagnostics, Diagnostics for the Real World, Human/PointCare, Iquum, Lumora, Mbio, Micronics, Northwestern Global Health Foundation, Partec, WAVE80 and Zyomyx

Thank you