The Well-Designed Study: How Validated Biomarker Measurements are Supporting Clinical Endpoints

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It is no secret that drug developers are under increasing pressure to discover new targeted therapies to meet high unmet medical needs, and to design clinical trials that will minimize the risk of failure to gain commercial approval. As research on diseases like Duchenne Muscular Dystrophy continues to progress, so does the demand for more sophisticated therapeutic solutions. While this is not a new or surprising dynamic to anyone in the industry, it was no less a significant topic of consideration at this year’s annual World Muscle Society in St. Malo, France.

A well-designed study, supported by robust data, is a critical success factor for obtaining regulatory approval. While many factors go into designing multi-phase clinical trials, one of the most important is clear and measurable endpoints. Endpoints drive what is clinically meaningful about the therapy, the benefit a patient should expect to see. Without a clear and measurable way to demonstrate that improvement or benefit, chances of a successful approval by the FDA or other regulatory agency drastically decline.

To mitigate these risks, drug developers should interact early and often with regulatory agencies to obtain feedback on their overall study design, focusing on the appropriateness of the primary and secondary endpoints selected, the methods for measuring those endpoints, and, importantly, the validation of those methods of measurement. Robust method validation of approved endpoints will minimize the risk that data from a clinical trial will not be considered during evaluation of therapeutic efficacy by the regulatory agencies.

The utilization of biomarkers as quantitative data supporting the efficacy of a therapy or other indications of the success of clinical trial endpoints, is an accepted standard in clinical trials. As such, Flagship Biosciences leverages its Computational Tissue Analysis (cTA™) platform, using fit-for-purpose assays and sophisticated computer algorithms to provide objective, quantifiable, reproducible data from contextual tissue interpretations, to enable biopharma companies to make complex decisions with confidence. Flagship uses this technology to partner with drug developers to create biomarker strategies to validate clinically meaningful endpoints to help increase the likelihood of approval.

Flagship has partnered with Summit Therapeutics, to support their Phase II clinical trial PhaseOut DMD, examining the efficacy of their therapy, ezutromid, on patients with DMD. Using Computational Tissue Analysis of IHC assays provides quantitative biomarker expression data while maintaining the context of skeletal muscle tissue, providing information for the thousands of fibers contained in each section. This method measures two key biomarkers – utrophin and MHCd – to determine the impact of ezutromid on the regenerative state and, thereby, overall health of the muscle. Such tissue-based measurements may provide insight into therapeutic efficacy long before other endpoints, and may lead to shorter clinical trials in the future. Through its cTA platform, Flagship uses analytically validated tissue-based biomarker measurements to provide meaningful data in support of clinical trial endpoints.

The importance of validated endpoints in clinical trials is not a new consideration, but improved methods of validation are helping to support drug developers’ likelihood of successful approvals for new therapies. Flagship’s cTA platform can provide the rich, contextual biomarker data and biomarker strategies that allow pharmaceutical partners to make confident clinical decisions and accelerate clinical trials, bringing these much-needed therapeutics to patients sooner.

Crystal Faelan, PhD
Flagship Biosciences