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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - ThromboSLE (Accurate assessment of thrombosis risk in systemic lupus erythematosus)

Teaser

Summary

Patients with systemic lupus erythematosus (SLE) are at high risk for thrombosis, a major and life-threatening complication of SLE. Thrombosis in SLE is associated with poor outcome and is one of the main causes of death in SLE. Thrombotic events cause high healthcare costs, including direct cost for interventions and rehabilitation cost.
Good Biomarker Sciences Leiden (GBS) has developed ThromboSLE, an innovative test to assess thrombosis risk in SLE with high sensitivity and specificity. Before further investing into the development and commercialization of ThromboSLE, GBS wanted to conduct a feasibility study for final verification of the technological as well as economic viability of the product.

Work performed

For the technological feasibility GBS aimed to show (a) that a positive correlation between the anti-dsDNA levels in SLE and tissue factor (TF) generation exists and (b) that TF generation may be used as a marker for thrombotic risk assessment in SLE patients.
The in vitro assay was developed and optimized for tissue factor generation in presence of artificial assembled immune complexes, validated with human plasma collected from healthy subjects, and TF generation was measured in patient material.
The results show that that TF can be generated by the reporter cell line in presence either of anti-dsDNA antibody or immune complexes. Therefore, the assay in this format represents a promising tool for assessment of the direct effect of anti-dsDNA autoantibodies isolated from patient material on TF generation by reporter cell line.
To assess the commercial attractiveness of ThromboSLE as a service versus offering the test as an IVD kit, user needs were defined through surveys with key opinion leaders (KOLs) in the field, market research was performed, the regulatory roadmap was defined, and potential market barriers were identified, such as the use of a cell line bought at ATCC for this commercial product.

Final results

Data obtained during this project neither support nor oppose our hypothesis regarding the risk estimation in SLE patient by evaluation of the relation between anti-dsDNA autoantibodies and TF generation by reporter cell line. Future experimentation must investigate technical solutions that will prevent clotting and grant collection of material suitable for downstream processing in order to measure TF.

Also, as a result of the technology feasibility assessment it has become clear the development of an IVD kit of the ThromboSLE test is not feasible on short term. ThromboSLE will therefore only be offered as a diagnostic service. At the same time, is was confirmed by the KOLs that they would ultimately see the ThromboSLE test as in IVD that they can apply in-house. An alternative method to develop a cell-free test method is therefore a major focus of GBS.

Based on the feasibility assessment, the clinical need for a better test to assess the thrombotic risk in SLE was confirmed. The requirements of the users with regards to test performance could be clearly defined. Key stakeholders and key elements for successful market uptake were mapped. Based on this, a list of activities was defined that will be pursued by GBS for the exploitation of ThromboSLE after the development and clinical validation was completed. Regarding the use of the commercial cell line, an ATCC Licensing Inquiry Letter was submitted to obtain information on costs and terms and is currently under revision at ATCC.