A Kidney Injury Biomarker Initiative

Biomarker research holds the potential for developing new, more accurate and powerful IVDs.

Evidence has been accumulating that several novel biomarkers will become powerful clinical tools for detecting treatment-induced acute kidney injury (AKI) and diagnosing impaired kidney function.1 In 2004, FDA launched the Critical Path Initiative (CPI) with the purpose of improving drug development.2 In order to support CPI, the Critical Path Institute, an independent non-profit institute, was developed in 2005 to facilitate collaboration among FDA scientists, academia, and industry for the sake of public good. In 2006, the Critical Path Institute announced the Predictive Safety Testing Consortium (PSTC), a public-private partnership with the specific aim of bringing together pharmaceutical companies to share and eventually improve the current safety testing strategies for drugs in development.

CPI inspired Pacific Biomarkers Inc. (Seattle) to develop a biomarker validation strategy that would identify novel biomarkers useful for assessing the drug-induced toxicity of drugs in development.3 Following detailed analytical validations, the biomarkers qualified in this program would be used in clinical trials with the goal of becoming accurate and powerful IVDs that would either replace or augment less sensitive tests. This article will summarize the work that Pacific Biomarkers has initiated, describe some individual biomarkers in the program, and outline their utility as potential IVDs.

Aims and Approaches
The current costs associated with drug development from discovery to final approval have been estimated to be $1 billion or more.4 Drug-induced organ toxicity accounts for 30% of all drugs that fail prior to reaching the market.5 The sooner such toxicity is discovered, the sooner further development costs can be curtailed, enabling drug developers to focus on other safer drugs. Early detection of organ toxicity would not only reduce the cost of drug development but also avert injuries to patients involved in clinical trials.

Thus, an appropriate acute organ injury biomarker panel has the potential to detect organ-specific toxic drug effects that currently are being missed in clinical trials. The early detection of organ injury in clinical trials could reduce drug development timelines by a number of years. Such detection might also reduce overall healthcare costs if organ injury could be diagnosed early enough to avoid severe and costly complications in patients using the drug after it is approved.

The key strategic goal of Pacific Biomarkers’ program is to provide pharmaceutical and biotech companies with services for testing robust novel biomarkers that have undergone thorough analytical validation and clinical qualification to diagnose early organ injury. This kind of work is now being conducted in response to recommendations by FDA for improving drug development as outlined in CPI, which currently is moving forward under the direction of PSTC and the Health and Environment Sciences Institute.2

CPI’s aim is to characterize not only the analytical performance of such novel biomarkers for detecting organ injury but also their clinical performance through collaborations among various pharmaceutical companies. The anticipated qualification of organ injury biomarkers will ultimately demand the development of stringent standardization procedures, which currently are nonexistent. As this article will discuss in the following sections, the analytical performance of some AKI biomarkers has already been characterized while the validation of others is underway.

The best approach to accomplishing the goals of the CPI program is to validate each biomarker using rigorous protocols for singlicate assays that generate the most robust data possible. During this process, modifying the assay methods or validating new ones may be necessary. Solid analytical performance is necessary to ensure that the data generated from the studies evaluating the novel biomarkers provides the best possible basis for choosing appropriate biomarkers for further development. Once a panel of 5-7 biomarkers with strong clinical performance has been identified, investigations on multiplex procedures for these biomarkers can be initiated.
Unfortunately, for many biomarkers, analytical performance deteriorates significantly during multiplexing. Nevertheless, testing multiple biomarkers at the same time using a multiplexed design is crucial for some physiological conditions. The obvious advantage is a comprehensive analysis of one particular pathophysiological pathway. However, this approach may reduce the overall analytical performance of the examined biomarkers, thereby reducing the data’s utility.

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Source: IVD Technology