Personalized Drug Response: IMplementation and Evaluation in CKD

Project Information

PRIME-CKD

Grant agreement ID: 101095146

DOI

10.3030/101095146

EC signature date 30 November 2022

Start date 1 January 2023

End date 31 December 2027

Funded under

• Health

Total cost

€ 9 242 241,01

EU contribution

€ 9 242 240,51

Coordinated by

ACADEMISCH ZIEKENHUIS GRONINGEN
Netherlands

Periodic Reporting for period 2 - PRIME-CKD (Personalized Drug Response: IMplementation and Evaluation in CKD)

Reporting period: 2024-07-01 to 2025-12-31

Summary of the context and overall objectives of the project

Chronic Kidney Disease (CKD) is one of the major causes of death in high income countries and its prevalence is growing rapidly. New therapies for the treatment of CKD have shown clear efficacy at a population level. Yet, individual patients respond differently with many patients showing suboptimal efficacy. This indicates that a ‘one size fits all’ approach is no longer sustainable. Currently there are no validated biomarkers (i.e. signal-substances that can be measured in blood or urine) in patients with CKD that aid in guiding optimal therapy for individual patients. Furthermore, there remains a large gap between biomarker research and actual implementation of biomarker based care in daily clinical practice. Thus, there is an urgent need to validate biomarkers and implement them in daily clinical practice. PRIME-CKD has a unique advantage to address this challenge as it builds on recent discoveries of new biomarkers to help guide optimal treatment to individual patients. The PRIME-CKD consortium has access to a vast amount of clinical data, bio-samples in order to:

1) Provide a breakthrough in the pharmacotherapy of CKD with the validation and implementation of pharmacodynamic biomarkers which will advance personalized medicine.
2) Scientifically validate innovative clinical trial elements, pipelines and qualification procedures that can be used by researchers, diagnostics industries and regulatory authorities.
3) Establish a Stakeholder Network to truly engage patients, clinicians and other stakeholders in implementation of personalized medicines
4) Develop a roadmap for biomarker use in daily clinical practice for the optimal treatment of CKD. These results will enable clinicians to match patients with CKD with the most effective available drug within the shortest possible timeframe leading to less disease burden and progression of disease, enhanced quality of life and increased cost-efficiency.

PRIME-CKD results will thus unlock the potential of biomarkers in healthcare and close the gap between biomarker research and clinical use in daily practice.

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

In the first 36 months of the PRIME-CKD project, significant progress has been made; we completed the first clinical PRIME-CKD study (UVALID), designed for the validation of the pharmacodynamic response biomarkers (WP1). Furthermore, in existing clinical trials (WP2), we validated uCLU as a pharmacodynamic biomarker for assessing treatment response to atrasentan in the data of the SONAR-, Spartan- and PROTECT trials. We have shown that uEGF was significantly associated with lower risk of kidney disease progression in patients with T2D with and without CKD in the CANVAS, CREDENCE, CANPIONE, DAPA-CKDtrials. We then advanced the validation of uEGF in clinical practice databases and completed the measurement of uEGF in the German CKD cohort in 5000 participants. With the completion of more than 30000 urinary clusterin and EGF measurements, we finalized work package 2 and completed the retrospective validation of the two biomarkers. Several scientific papers are published, in press or in development describing the results and implication of the findings to support implementation of these biomarkers in clinical practice.

We demonstrated that a cut-off for response of -30% for uCLU and 0% for uEGF is an optimal response threshold, which seems clinically applicable. This evidence currently proves the efficacy of treatment to the clinicians and patients in our upcoming clinical trials. These thresholds form a future basis for the evidence-based tools for clinical implementation and are thus crucial for holistic roadmap for clinical practice implementation. Two PRIME-CKD partners (RENALYTIX (REN) and REGIONH (STENO)) have announced a partnership to implement a new biomarker risk algorithm in all REGIONH (STENO) practices in Denmark. This is a big step forward in achieving a personalized medicine approach for patients with CKD and a prime example for how the PRIME-CKD consortium provides clinicians and patients with evidence-based tools to personalize medicine.

PRIME-CKD has actively participated and contributed to the companion diagnostics community, reaching out to researchers, healthcare providers and companies globally with the establishment of the PRIME-CKD Stakeholder Network. As an example, consortia members support with validated procedures, data and experience a diagnostic company that develops a new assay to measure the Glycocalyx. Additionally, advice and consultancies have been given to various start-ups pharma companies in Europe as well. Through the stakeholder network we have been able to secure finerenone medication for free for the CKD Biomatch study in WP3. The extensive networks of the project partners have facilitated the already existing personal and business accounts to reach diverse stakeholder groups. PRIME-CKD scientists have started to work on a roadmap and are collecting experiences with respect to diagnostics and biomarker validation to present this to stakeholders at the completion of the project.

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)

In the first 36 months of the PRIME-CKD project, significant progress has been made towards achieving one of the overarching aims of PRIME-CKD: to validate and register recently discovered pharmacodynamic response biomarkers of individual response to existing drugs for the treatment of CKD. The achievements accomplished in the first 36 months of PRIME-CKD project are crucial for the project’s success and demonstrate our commitment to advancing CKD research.