Establishment of a Neutrophil elastase Activity home test for the Better management and treatment of Lung Exacerbations

Project Information

ENABLE

Grant agreement ID: 651158

DOI

10.3030/651158

Project closed

EC signature date 26 September 2014

Start date 1 October 2014

End date 31 March 2015

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 71 429,00

EU contribution

€ 50 000,00

Coordinated by

PROAXSIS LTD
United Kingdom

Periodic Reporting for period 1 - ENABLE (Establishment of a Neutrophil elastase Activity home test for the Better management and treatment of Lung Exacerbations)

Reporting period: 2014-10-01 to 2015-03-31

Summary of the context and overall objectives of the project

ProAxsis, is developing a range of products for the capture, detection and measurement of active protease biomarkers of disease.
Our rapid and easy-to-use tests incorporate patented “ProteaseTags™”; smart molecules which trap an active protease within a complex biological sample and enable a visual readout of its presence. A number of active protease species have been extensively validated as biomarkers of disease activity in areas such as cancer and infection, in addition to respiratory diseases such as cystic fibrosis and COPD.
Chronic obstructive airways disease (COPD) is a leading cause of death of increasing prevalence worldwide and is characterised by progressive airflow reduction, breathing difficulties and irreversible lung damage. Management of COPD varies extensively, with patients not receiving proactive disease management at greater risk of poorer outcomes. Routine measurement of an active protease (enzyme) biomarker called neutrophil elastase (NE) will empower clinicians and patients to adopt proactive approaches to disease management and treatment, reducing exacerbations and emergency hospital admissions.
Our goal is therefore to develop a novel, simple to use ‘Point-of-Care’ (PoC) test that will improve patient outcome and reduce the clinical, societal and economic burdens associated with chronic respiratory disease (CRD). The activity of NE (NEa) in the airways is known to correlate with the severity of several CRDs such as COPD, cystic fibrosis (CF) and non-CF bronchiectasis, and importantly is highly predictive of infection and an early marker of exacerbation. Our novel device, NEATstik™ (Neutrophil Elastase Airways Test), will enable the rapid measurement of NEa at PoC and has been designed for home use (patient self-management) in mind, with a view to remote monitoring. It is expected that this test will help to improve patient management and outcome, with the ultimate goal of reducing the individual, European and global burden of COPD.
To pursue the development and clinical validation of NEATstik™ the following Phase 1 feasibility study was conducted to ENABLE the elaboration of our business plan.
ENABLE (Establishment of a Neutrophil elastase Activity home test for the Better management and treatment of Lung Exacerbations) had two specific objectives:
1) Preparation for product validation to include specialist advice from a recognised clinical trials authority for the design of a clinical trial to validate the clinical performance of NEATstik™ (to be conducted in Phase 2: MONITOR: Measurement Of Neutrophil elastase In the management and Treatment Of chronic Respiratory disease).
2) The development of an innovation strategy to ensure financial viability, market readiness and growth.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

ENABLE included an assessment of feasibility and the development of an innovation strategy to support the clinical validation of NEATstik™; to ensure optimal integration of the device into the clinical management of COPD patients, and to enable success of this first to market product.
The technological/practical feasibility was addressed by obtaining specialist advice from recognised clinical trials units and clinicians for the design of a clinical trial to validate the clinical performance of NEATstik™ which will be executed in Phase 2 (MONITOR study). Expertise on trial design and management, including statistics, data management, monitoring and health economics was sought. This also included the identification of suitable clinical partners across Europe for MONITOR.
Regulatory affairs advice was obtained to include information regarding CE marking to ensure our product, NEATstik™ complies with all the essential requirements of relevant Directives, prior to MONITOR. A risk assessment was also conducted.
The economic viability of our programme included the development of an innovation strategy to ensure market readiness and growth. Staff training and development was reviewed as well as an assessment of market opportunities with a focus on pricing, time and routes to market addressing in particular access to European healthcare systems and any potential barriers to entry. Scalability of production/manufacturing was assessed to meet potential demand and options for distribution.
The study also included a review of our IP management: over and above IP secured on core technology and an overall financial feasibility assessment was conducted.
The technical and economic assessments of our innovation programme towards the delivery of a point of care test, NEATstik™ for the management of chronic respiratory disease have provided us with the resources necessary to drive forward and execute a Phase 2 application which will support the next stage of commercial development.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

COPD is a global challenge of significant magnitude as it is the only leading cause of death which is increasing in prevalence worldwide. COPD is a combination of chronic bronchitis and emphysema resulting in progressive airflow limitation and consequently difficulty in breathing. Currently, there are on average 3.3 M deaths worldwide (250,000 across Europe) and by 2020 COPD is likely to account for over 6 million deaths which will make it the third leading cause of death. There is therefore a real need for impact in terms of prevention, treatment and management.
The frequency of clinically relevant COPD varies from 4-10% across Europe (in the UK 3 million people are estimated to have COPD rising to 30 million across Europe). In the US, close to 24 million adults have evidence of impaired lung function, of which 15 million have been diagnosed with COPD. Lung damage in COPD is progressive and irreversible.
A key area to address the EU/global COPD challenge is to reduce the number of acute exacerbations in COPD which require hospital admission and are known to accelerate the progressive decline in lung function associated with COPD. It is estimated that a 5% decrease in the number of hospital episodes for COPD could lead to a saving of £15.5 M (€20 M) pa within the UK. In addition, by stalling the progression of the disease through more proactive management, the burden to the individual could be significantly reduced as even mild disease can lead to reduced activity and result in co-morbidities such as coronary heart disease.
NEATstik™ is targeted against a clear unmet clinical need for a diagnostic test that identifies chronic respiratory disease patients at high risk of impending exacerbation and would enable early interventional, personalised treatment, bringing in significant clinical and cost benefits to the management of these patients. Neutrophil elastase (NEa) is predictive of infection and inflammation with a prodromal phase estimated to be up to 2 weeks before the patient is fully symptomatic to the point that medical intervention is sought. A long-standing challenge has been an ability to measure active levels of protease outside of an academic research laboratory.
Our patented ProteaseTag™ methodology incorporated into a lateral flow device (NEATstik™) will provide opportunity for patients to monitor NEa in their airways, the early detection of which may predict a potential exacerbation, allowing for the early prescribing of antibiotics (oral vs hospital-administered i.v.’s) thus reducing hospitalisations with clear economic benefits which will contribute to the sustainability of the health care system. Substantial benefit would also be apparent to the patient due to a reduction in the number of acute exacerbations which are significantly associated with pulmonary decline and irreversible lung tissue damage. Personal patient monitoring and management could also contribute significantly to a “connected health” approach as well as the establishment of a stratified medicines programme.

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