Nairobi, Sept 13th-15th 2018

New diagnostics to improve diagnosis of liver disease

Francesco MARINUCCI,

Head HIV/HCV Programme

FIND

Financial disclosure

Nothing to disclose

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Outline

Intro FIND

New diagnostic to improve diagnosis of liver disease: a public health approach

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FIND – an innovative partner in diagnostic solutions for

LICs and LMICs

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FIND is a non-for-profit NGO that was founded in 2003

FIND mission: turning complex diagnostic challenges into simple solutions to overcome diseases and

transform lives in developing world

Key focus areas: TB, malaria, HCV, HIV, Fever and Anti Microbial Resistance, Neglected Tropical Diseases,

Outbreaks

Today, FIND offers a full package of support to develop and subsequently turn a diagnostic test into a

diagnostic solution

Catalyze development

•Dynamic needs definition with global stakeholders

•Scout technologies

•Support fit-for-purpose product development

Guidance of use and policy

•Define evidence needs

•Lead clinical trials

•Support the development of WHO guidelines

Accelerating access

•Collaborate with governments, MoH, different implementation partners to support rapid uptake of the developed products

•Develop locally appropriate QA plans

Shape agenda

•Measure and communicate the impact of diagnostics

•Shape diagnostics ecosystem to foster willingness to invest/pay

•Lead global discussions on emerging diagnostics

FIND approach

Working with 185 partners globally and forming coalitions, always with the end in mind

Industry

• 46 partners

Universities and Research

Institutes

• 44 partners

Clinical Trial Sites

• 32 partners

Implementing partners

• 26 partners

Advocacy

• 4 partners

Government/ multilateral agencies

• 35 partners

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New diagnostic tools for a public health approach

Nairobi, Sept 13th-15th 2018

WHO simplified testing algorithm for hep C triggered public

health response to viral hepatitis need for more appropriate tools

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E• Variability in performance

• Lack of quality-assured

RDT

• Lack of QA/QC systems

• No EQA

• No decentralized solution

• Lack of testing labs

• Long turnaround

• High cost

• Weak QA/QC systems

Unmet needs and prioritization

Reference

centre

District

hospital

Health

centre

Health

post

Community

health worker

POC viremic test for diagnostics, monitoring and/or test of cure

Optimizing existing and developing new screening tests

Integrate VH testing in HIV/TB programmes

Published TPPs N/A

DBS sampling

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Increasing affordability and access

True POC or platform-free test

FIND Hepatitis C Elimination through Access to Diagnostics

(HEAD-Start): bridging the gap between R&D and country adoption

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Area Target FIND work Timeline

Using existing tools for decentralizing HCV Dx

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Multicentre clinical evaluation conducted in 2017-2018 in 5 countries in various healthcare settings and

high risk populations including HIV-coinfected showed high sensitivity and specificity of new Xpert

Fingerstick HCV VL Cepheid GeneXpert Fingerstick HCV VL test can be used as a one-step diagnostic

solution

The possibility to detect HCV viraemia from a drop of capillary blood in one hour will facilitate

decentralization of testing and thereby expand access to care

Detection of

HCV RNA using

finger stick

whole blood

Georgia, Cameroon, Greece, US, Malaysia

11FIND study: evaluate performance in level 1-2 facilities

Needs plasma separation

Manual steps

Turnaround time 90’

Easy-to-use instrument,

small footprint

https://www.finddx.org/news/genedrive-partners-find-evaluate-molecular-diagnostic-

kit-hepatitis-c-virus-decentralised-settings/

Near-POC HCV

tests in

validation/impl

ementation:

GeneDrive

Using existing tools for decentralizing HCV Dx - CONTINUED

DBS sampling for HCV RNA test

Aim: provide HCV diagnostics in the settings with no access to laboratory infrastructure

Concept:

Advantages: ease of transport, possibility to gather with other tests, increased opportunity for HBV and HCV

testing and treatment follow-up in hard-to-reach individuals and people living in rural areas

Disadvantages: long turnaround time, high cost of testing

Need: strong dataset to allow confidence in the test performance from DBS

Trigger: manufacturers obtained analytical data on test performance from DBS, ready to contribute in kind

with test kits and training, expressed interest to submit regulatory claim for DBS

FIND activity: Design, prepare and conduct multicentre clinical trial

Validation of DBS sampling: a key step to scale up nucleic acid testing and

accelerate integration on polyvalent high-throughput platforms

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HCV RNA test

FIND Hepatitis C Elimination through Access to Diagnostics

(HEAD-Start): bridging the gap between R&D and country adoption

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Area Target FIND work Timeline

Three-pronged strategy for product development: reducing

the risks and improving the chances of success

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Advantages: Disadvantages:

Molecular test

• Low technical risks: high likelihood of

success

• Highest sensitivity and specificity

• Has a clear market in the US and Europe

• Cost of goods is high

• Stability of reagents (particularly,

enzymes) is often an issue

• Needs rather complicated, heavy and

costly instrumentation

Core Antigen

test on

immunoassay

platform

• Likely lower cost of goods as compared to

molecular test

• Bringing high-sensitive POC

immunoassay platform to the market that

can be possibly used to develop other

assays with high performance

requirements

• Technically challenging given sample

processing and signal amplification needs

• Cost will be higher than RDT

• Potential for integration with testing for

other diseases is not clear

Dual Ab/Ag

test on RDT

• Lowest cost

• Instrument-free or requires only simple

one-button reader device, i.e. greatest

decentralization potential

• Ag-part will have suboptimal sensitivity so

Ab-positive/Ag-negative results require

confirmatory testing

• Technically challenging given sensitivity

requirements and the necessity to

integrate sample processing step

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Aim: bring affordable and easy-to-use POC HCV diagnostic solution to decentralize HCV testing

Concept:

TPP: https://www.finddx.org/wp-content/uploads/2016/01/HCV-TPP-Report_17July2015_final.pdf

Attribute Optimal Minimal

Target operator Community workers with minimal training Healthcare workers/technicians with limited training

Sample preparationFully integrated sample-to-answer

Integrated specimen preparation; not more than 2

manual steps required (no precision volume control and

precision time steps)

Portability Small, portable or hand-held, device, ≤5 kg Small table-top device

Analytical sensitivity <200IU/mL <1000 IU/mL

Time to result ≤30 min <90 min

Assay COGS <7 USD <15 USD

POC HCV

viraemia test

Level 1-2: near-POC

Level 0: true POC

Target Product Profile for game-changing POC solutions:

what we will be able to achieve

On going process that recently moved into feasibility

studies of various technologies

Following the conclusion of an extensive Request for Proposal process on World

Hepatitis Day 2018 FIND announced the award of grants for feasibility studies

Grants for feasibility studies to be awarded to Abbott, BLINK-DX, and Diagnostics for

the Real World for the development of a molecular point-of-care (POC) test for

hepatitis C virus (HCV) RNA detection; and Chembio Diagnostics, Mologic and DCN

Diagnostics for development of an HCV core antigen rapid diagnostic test

2 other partners to develop HCV cAg assay will be announced in September 2018

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https://www.finddx.org/news/find-announces-new-wave-activities-addressing-

challenges-threatening-hepc-elimination/

FIND Hepatitis C Elimination through Access to Diagnostics

(HEAD-Start): bridging the gap between R&D and country adoption

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Area Target FIND work Timeline

Innovation also entails optimizing the use of current

tools: TREAT B score

New diagnostic score was developed using a large

dataset of African patients

Positive HBeAg and ALT level as independent

predictors of the EASL treatment eligibility

Diagnostic accuracy of the score for selecting

patients for HBV treatment was high

The score may facilitate scale-up of treatment

programs in LMICs

• Both ALT and HBeAg measurements are widely available in

LMICs

• User-friendly and may enable a task shifting

• only one blood sampling is required

• very flexible for its use i.e. the cut-off value can be adapted to the

local context

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https://www.journal-of-hepatology.eu/article/S0168-8278(18)32102-0/fulltext

Simple methods to detect liver disease at the point-of-care (POC)

are urgently needed as part of the global effort to eliminate VH

https://www.burnet.edu.au/projects/170_alt_point_of_care_diagnostic_to_detect_liver_disease

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ALT point-of-care diagnostic to detect liver disease1

• A POC test developed by Burnet Institute

spinoff company, Nanjing BioPoint Diagnostic

Technology (Nanjing BioPoint)

• Field studies on the use of the ALT test will

start in late 2017, initially in patients infected

with hepatitis C where it is important to

determine the level of liver disease to guide

appropriate antiviral therapy

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http://dfa.org/liver-function/

Low-cost, patterned paper-based, liver enzyme

diagnostic test2

Simple methods to detect liver disease at the point-of-care (POC) are urgently needed as

part of the global effort to eliminate VH - CONTINUED

• Developed by Diagnostics-For-All (DFA), non-profit

enterprise fusing biotechnology and device development

• Relevant laboratory and field studies to demonstrate the

liver function test's effective use in a low-resource setting

• Class I exempt status for its LFT-ALT testing system

• FDA Establishment Registration

• Preparing to submit for regulatory approval for Point of

Care Use (on going)

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Simple methods to detect liver disease at the point-of-care (POC) are urgently needed as

part of the global effort to eliminate VH - CONTINUED

A paper-based multiplexed transaminase test for low-cost,

point-of-care liver function testing3

• The device consists of two layers of similarly patterned

paper, a plasma separation membrane, and a laminated

cover of polyester film

• Fingerstick specimen or 30 μl of a specimen obtained by

venipuncture

• After 15 min, the AST and ALT test zones are matched to a

color “read guide” to obtain a concentration value

• Results are interpreted as being within one of three “bins”

of values

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624093/

To be effective the new tools have to be embedded into in

replicable models to achieve health impact globally

Common challenges in access, but no

one-size-fits all solutions…

…require "smart" response based on

replicable models

Access stakeholders, especially donors,

looking for effective solutions for uptake

Yet, country-specific barriers to uptake

Standard operational features dev. once

Processes developed once but tailored

to context specificities

Proven impactCost-effectiveness

& replicability

Health systems and

patient pathways

Community and

cultural contexts

E.g., technologies E.g., training kits

E.g., policy updateE.g., stakeholder

engagement plan

Thank you

Asante sana