Drug development for rare diseases presents a range of unique challenges across all stages, including discovery, development, and ensuring affordability for patients. One significant opportunity in this process is developing and utilizing appropriate biomarkers as clinical endpoints to identify suitable therapeutic targets and select optimal clinical doses that align with targeted production profiles.
The complement system, a vital element of the innate immune response, plays a crucial role in eliminating pathogens and cellular debris. However, when the complement system is dysregulated, it can contribute to the development of multiple rare diseases.
Recently, a novel biopharmaceutical protein has been under development for the treatment of complement-mediated diseases. This protein is a small fusion protein with dual specificity, consisting of a domain that binds strongly to complement component 5 (C5), effectively inhibiting terminal complement activation. Additionally, it incorporates an albumin-binding domain that extends the protein's plasma half-life by targeting plasma albumin. The concentration of free C5 (unbound C5) has been selected as a clinical endpoint to evaluate the efficacy of this anti-C5 molecule.
During the early stages of clinical development, the concentration of free C5 played a critical role in two key decision-making processes. Firstly, the clinical dose was selected to ensure that the levels of free C5 met the threshold recognized by the FDA. Secondly, a rare disease was chosen based on the free C5 profile and complement activities associated with the disease condition. Moreover, since the endogenous C5 level is relatively high (approximately 100 μg/mL), having a reliable quantitative assay to measure free C5 levels is crucial for the success of this program.
This presentation will delve into the essential considerations, challenges, and approaches involved in the development of clinical biomarkers for rare disease drug development.
Learning Objectives:
Learn and understand the challenges related to rare disease drug development and the potential use of biomarkers for clinical studies.
Will learn from the case study of C5 for complement inhibitor, how biomarker assays were developed, validated, and deployed, how the data was analyzed, clinical trial design, and data analysis.
Understand and apply how to review and analyze biomarker data in the context of clinical effects, the analysis methods, and the consideration of indication selection based on the biomarker results.