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Biomarkers for clinical assessment of lungs intended for transplantation

Periodic Reporting for period 1 - BMEVLP (Biomarkers for clinical assessment of lungs intended for transplantation)

Reporting period: 2014-11-01 to 2015-04-30

People are still dying while waiting for receiving lung transplantation. In Scandinavia alone, 46 persons died over the last three years. With more available lungs, those persons might have been alive today. This is only half the truths as it is expected that with more available lungs, more persons with terminal lung diseases would be placed on the waiting list and receive new lungs and an improved life. This EU-project aimed at improving the selection process of donated lungs. This is important as today only about 20 - 25% of donated lungs are being transplanted. The remaining 75 - 80% are discarded, most of the time due to an unsure quality. Ex Vivo Lung Perfusion (EVLP) is a technique developed to evaluate the functionality of lungs after removal from the donor, but before transplantation. The lung is circulated with a warm solution and ventilated with a conventional ventilator, which allows the clinicians to investigate how well the vasculature and the alveolar performs its basics task of gas exchange. All is done in a controlled environment not to pose a risk of damaging the lung during the procedure. The safety of EVLP has been proven in clinical studies performed in the US, Austria, Canada and otherwise. In fact, some clinical data suggests that the procedure even offers protective effects to the lung as the reperfusion (re-entering) of circulated blood (solution), is done in a more careful way, than what can be done in a patient. If this beneficial effect is significant, it means than not only do more patients receive lungs, the lung transplantation patients might also have a longer and healthier life after the transplantation, than what they would have had with conventional lung transplantation.

EVLP has proven its clinical value to increase the number of lungs available for transplantation. Within the first years, the increase, at a center level, is about 30% more lung transplantations generated through EVLP. The limit with EVLP is that the analysis is partly based on subjective criteria. This is acceptable as long as the technique is only used by the most experienced centers, but with dissemination of the technique, more objective parameters would facilitate the use of EVLP and increase security in term of organ function. This project aimed at identifying objective markers of lung function during EVLP. Although a clinical trial is required to determine the success of the project, initial data support the view that significant biomarkers have been identified within the project.

The project has also thoroughly investigated the user needs and it has identified different technology platforms that could be used to improve the objectivity of the EVLP-process. All in all, the project has generated a strong position for future development of EVLP and therefore to offer more lungs to dying persons.
With a scientifically based approach a list of potential biomarkers with diagnostic value during EVLP has been drafted. The proposed biomarkers have then been ranked based on clinical potential, safety, innovativeness and marketability.

An investment analysis and business plan has been drafted for the proposed biomarkers.

A feasibility study has been performed to investigate the operability of the proposed biomarkers.

From an extensive list, a handful of biomarkers passed all the required tests to become selected biomarkers for a clinical study. This means that they are believed to improve the selection process of EVLP, while being innovative and possible to bring to the market after clinical evaluation and technical adaptation.
The potential impact for the society is decreased waiting time for lung transplantation and therefore decreased morbidity and mortality associated with the waiting. Possibly also an improved post-transplantation life expectancy and health might be achieved, however, that requires further clinical long-term studies. Decreased mortality and morbidity, due to access of lungs for transplantation, for persons with terminal lung diseases is not only to benefit for the diseased, but their treatment also imposes a substantial societal burden that would be reduced. More than a doubling of lung transplantations world-wide as well as in Europe is anticipated to be achievable with a successful phase 2 project.

Even at this stage an improved understanding of the lung function during EVLP could improve the selection process of donated lungs which in turn could save lives, both through a select and a de-select process. Moreover the work in the project has generated new knowledge and understanding about the clinicians needs and how to get about to support the clinicians needs in term of lung evaluation during EVLP. By pursuing this project further, XVIVO will continue to grow and to develop new and innovative products to facilitate the clinicians’ decision about whether to transplant a lung or not and thereby help the clinicians to save more lives with lung transplantation.