Periodic Reporting for period 1 - PRIME-CKD (Personalized Drug Response: IMplementation and Evaluation in CKD)
Reporting period: 2023-01-01 to 2024-06-30
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.
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.
In the first 18 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 Duplex 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 and CREDENCE trials. Ongoing- and upcoming measurements of additional clinical trial data are anticipated to offer further validation of these findings. These achievements are crucial for the project’s success and demonstrate our commitment to advancing CKD research.
In WP2, 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 and STENO) have announced a partnership to implement a new biomarker risk algorithm in all 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 established the PRIME-CKD Stakeholder Network (WP6). 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.
In WP2, 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 and STENO) have announced a partnership to implement a new biomarker risk algorithm in all 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 established the PRIME-CKD Stakeholder Network (WP6). 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.
In these first 18 months we have primarily been collecting data. Results beyond state of the art are expected in year 2 and 3 of the project