Periodic Reporting for period 6 - TransBioLine (Translational Safety Biomarker Pipeline (TransBioLine): Enabling development and implementation of novel safety biomarkers in clinical trials and diagnosis of disease)
Periodo di rendicontazione: 2024-02-01 al 2025-01-31
TransBioLine has pursued the clinical validation and regulatory qualification of safety biomarkers to be used in drug development and clinical care to address monitorability and treatment of drug-induced injury. More specifically, during this 6 year project, TransBioLine’s 5 organ work packages studying drug-induced organ injury of the kidney (WP1-DIKI), liver (WP2-DILI), pancreas (WP3-DIPI), vasculature (WP4-DIVI), and nervous system (WP5-DINI) have successfully developed research plans and obtained regulatory endorsement thereof, analytically qualified organ panels often with novel cross-species platforms and/or novel analytes, performed pre-clinical studies for biomarker discovery and development, prospectively enrolled patients in newly initiated clinical studies using largely harmonized Patient Information Sheets and Informed Consent Forms, completed learning phase studies, and completed initial interpretation of final datasets. In parallel, processes were developed to ensure proper use and future sustainability of the sample and data sets generated during the project. The robust datasets generated by each team have lead to novel insights in the performance and behavior of a roughly 50 biomarker candidates in various disease states as well as normal healthy volunteers. Findings that have not yet been published will be disseminated after the project runtime, to continue to support ongoing and future regulatory qualification efforts to support the adoption of promising biomarkers. Overall, these efforts will continue to support streamlining drug-development efforts, ensuring patient and volunteer safety in clinical development, improve our mechanistic understanding of toxicities caused by medications, and assist clinicians in the assessment and treatment of patients with renal, hepatic, vascular, pancreatic, and nervous system injury.
All organ WPs have obtained FDA and EMA guidance and support in regulatory submissions. WPs 1, 2, 4, and 5 Letters of Intent have been accepted into the FDA Biomarker Qualification Program. EMA qualification advice has been received by all work packages. These initial formal interactions with FDA and EMA are in the public domain, which at the least paves the way for future qualification efforts. Further, WP5-DINI has submitted a Qualification Plan to the FDA and the EMA, and has received follow-up qualification advice from the EMA in year 6. The team is positioned to submit a full Qualification Package to the EMA within 1 year after completion of the project. WP2-DILI had a pre-LOI meeting with the FDA to discuss an LOI submission for the MetaHeps platform and is positioned to submit this LOI to the FDA, along with a Qualification Plan to the EMA and the FDA within 1 year after end of the project runtime. Organ WP members together with WP6-miRNAs, 7-Assays, and 8-Data worked successfully together to establish methods and procedures for sample collection, processing, storage, analysis, and data harmonization. TransBioLine datasets are fully mapped to SDTM, in preparation of submissions to health authorities as well as uploaded in TranSMART. The eCRFs for all clinical organ work packages have been completed and currently data from over 1700 subjects is loaded. The analytical platforms for miRNA signatures have been defined and established. miRNA raw data analysis processes have been established and disseminated (mIND pipeline) to robust and reproducible miRNA data analysis, technology and analysis available via TAmiRNA, Vienna, Austria. Protein biomarker assays have also been validated, available via Signatope, Reutlingen, Germany and MLM, Moenchengladbach, Germany. The biobank and database contain samples and data for over 1700 and 2000 subjects available for future research via ZeBanC, Berlin, Germany and ITTM, Esch-sur-Alzette, Luxembourg, respectively, and processes have been established for the continued Use and Access of samples and datasets beyond the project runtime to consortium and external requestors alike, in a cost-neutral manner, respecting legal and ethical constraints. Information is available on the TransBioLine website.
The biomarkers being developed by TransBioLine will ultimately greatly enhance clinical care, and patient safety and well-being, and streamline drug-development. If qualified, they will aid in drug development in the near future, where, and implemented under regulatory guidance driven by the data collected and presented by TransBioLine to regulatory agencies, the biomarkers will be elemental in driving the development of efficacious and safe medications. These will in the long term, in addition to increased use of novel sensitive and specific biomarkers in a clinical setting, have impacts across research, pharmaceutical industries, and public health sectors alike. TransBioLine activities in leveraging the project outcomes will continue well beyond the consortium runtime, as the expert network will remain intact and in collaborate beyond the project, as agreed upon by the majority of the consortium members at project termination. Full dissemination of findings across the work packages and additional regulatory submissions are planned in the coming year, and are expected to result in significant impacts on the field of biomarker research, adoption, and regulatory qualification and substantially improve diagnosis, management, and mechanistic understanding of drug toxicity and acute or chronic disease. Please see transbioline.com for more information.