Periodic Reporting for period 4 - ADVANTAGE (ADvanced Validation of A Novel TB Active disease diagnostic to address Global unmet needs: a European consortium approach)
Période du rapport: 2018-07-01 au 2019-03-31
Tuberculosis (TB) remains the single biggest communicable disease affecting 10.4m people in 2015 and causing 1.8m deaths globally. TB is preventable and curable, but despite significant investment and decades of research, diagnosis is not a simple procedure. The current tools available for the diagnosis have various limitations means that the diagnosis of active TB remains a long and difficult first step to its management. As Active TB is highly contagious rapid diagnosis and early start of treatment will help to prevent the spread of the disease. WHO has identified the need for a simple, rapid, POC blood test for TB suitable for use in a minimally resourced setting. It is this challenge that project ‘ADVANTAGE’ seeks to address.
The overall objectives of the three-year project are:
- Migrating the proof of concept from the laboratory to a potential POC platform
- Validating and improving the biomarker signature
- Retrospective clinical trials to confirm diagnostic accuracy
- Prospective clinical trials in Europe, Brazil and South Africa
- Commercial planning including regulatory readiness.
The overall objectives of the three-year project are:
- Migrating the proof of concept from the laboratory to a potential POC platform
- Validating and improving the biomarker signature
- Retrospective clinical trials to confirm diagnostic accuracy
- Prospective clinical trials in Europe, Brazil and South Africa
- Commercial planning including regulatory readiness.
With the support of the Horizon 2020 funding, to date, ProteinLogic has optimized its TB biomarker immunoassay panel, containing a much smaller number of analytes, meaning potentially much lower costs per test. The TB signature has further been enhanced by new diagnostic models, generated through the use of advanced Machine Learning techniques in collaboration with world-class biostatisticians. Most importantly, this unique signature has been clinically validated with a large, ethnically diverse, well-characterised, statistically significant patient sample cohort collected prospectively from TB clinics in London, UK.
The achieved performance of the test is a break-through. The level of accuracy exceeds that currently required by the W.H.O for a rule-out test for Active TB (sensitivity > 90%, specificity >70%). Crucially, the test has been shown to perform equally well for difficult-to-diagnose Extrapulmonary TB cases.
Throughout the project, ProteinLogic has been working directly with a potential Point-of-Care device to port its highly accurate diagnostic test onto, with significant equivalence achieved between the reference platform and the POC device for our signature, in terms of detection sensitivity, paving the way to the final product.
To further validate this platform, ProteinLogic has commenced the collection of samples from South Africa, Brazil, and European countries, adhering to strict ethical guidelines, and ensuring full ethical approval for all work. By the end of this project, it is expected that we will have prospectively collected and analysed over 2000 clinical samples from high burden countries and European TB clinics. Clinical studies of such magnitude are very costly, and one of the main barriers for the development of new in-vitro diagnostics, and it would not have been possible for ProteinLogic to commission these without the help of the Horizon 2020 funding we have received.
Finally, we have been developing a full regulatory plan, to include major countries of interest to access once the project has completed. The regulatory landscape globally for diagnostics is changing rapidly, and ProteinLogic has been keeping abreast with developments to ensure successful market access.
The achieved performance of the test is a break-through. The level of accuracy exceeds that currently required by the W.H.O for a rule-out test for Active TB (sensitivity > 90%, specificity >70%). Crucially, the test has been shown to perform equally well for difficult-to-diagnose Extrapulmonary TB cases.
Throughout the project, ProteinLogic has been working directly with a potential Point-of-Care device to port its highly accurate diagnostic test onto, with significant equivalence achieved between the reference platform and the POC device for our signature, in terms of detection sensitivity, paving the way to the final product.
To further validate this platform, ProteinLogic has commenced the collection of samples from South Africa, Brazil, and European countries, adhering to strict ethical guidelines, and ensuring full ethical approval for all work. By the end of this project, it is expected that we will have prospectively collected and analysed over 2000 clinical samples from high burden countries and European TB clinics. Clinical studies of such magnitude are very costly, and one of the main barriers for the development of new in-vitro diagnostics, and it would not have been possible for ProteinLogic to commission these without the help of the Horizon 2020 funding we have received.
Finally, we have been developing a full regulatory plan, to include major countries of interest to access once the project has completed. The regulatory landscape globally for diagnostics is changing rapidly, and ProteinLogic has been keeping abreast with developments to ensure successful market access.
During this period there has been a major break-through. Analysis of a large number of well-characterised clinical samples has successfully shown discrimination between active TB and non-TB samples, with a high degree of accuracy, including Extra-pulmonary TB. This achievement is unprecedented as the level of accuracy exceeds those currently required by the W.H.O for a rule-out test for Active TB (sensitivity > 90%, specificity >70%). A rule-out test for active TB is the top priority test in the fight to eradicate TB, as such a test has the potential to help clinicians quickly prioritise those patients with symptoms who are more likely to have Active TB. This would then lead to the treatment of those affected, thus reducing further spread of the disease. This break-through therefore indicates the huge potential of the biomarker signature. A conservative estimate of the annual global market for a rule out TB test is 80 million tests per annum at an estimated market value of >$1bn per annum.
The availability of a simple, rapid and affordable POC test for TB will have major impact on morbidity, mortality and economic wellbeing of affected individuals and families in the developed and developing world. The project has demonstrated the potential for utilising the ProteinLogic biomarker signature as the basis of an innovative ‘rule out’ test to discriminate between TB and non-TB. Results to date using high quality European clinical samples, indicate performance better than the W.H.O guidelines; this work is on-going with the objective of increasing accuracy (specificity) level even further.
ProteinLogic has been disseminating its promising results to experts in the relevant field. The impact of ProteinLogic's work was mentioned in a recent Unitaid Report, entitled “TUBERCULOSIS Diagnostics Technology Landscape 5th Edition, May 2017”. Members of ProteinLogic have attended conferences, institutional events, and scientific meetings throughout the project, facilitating discussions with Key Opinion Leaders in TB, as well as with NGOs assisting with the fight against TB. ProteinLogic will continue to do so to the end of the project, and beyond.
The availability of a simple, rapid and affordable POC test for TB will have major impact on morbidity, mortality and economic wellbeing of affected individuals and families in the developed and developing world. The project has demonstrated the potential for utilising the ProteinLogic biomarker signature as the basis of an innovative ‘rule out’ test to discriminate between TB and non-TB. Results to date using high quality European clinical samples, indicate performance better than the W.H.O guidelines; this work is on-going with the objective of increasing accuracy (specificity) level even further.
ProteinLogic has been disseminating its promising results to experts in the relevant field. The impact of ProteinLogic's work was mentioned in a recent Unitaid Report, entitled “TUBERCULOSIS Diagnostics Technology Landscape 5th Edition, May 2017”. Members of ProteinLogic have attended conferences, institutional events, and scientific meetings throughout the project, facilitating discussions with Key Opinion Leaders in TB, as well as with NGOs assisting with the fight against TB. ProteinLogic will continue to do so to the end of the project, and beyond.