Workshop Report: FDA Workshop on Improving Cardiotoxicity Assessment With Human-Relevant Platforms

Area of Science:

• Drug Development
• Toxicology
• Cardiovascular Safety

Background:

• Cardiovascular safety concerns are a primary reason for drug attrition during preclinical development.
• Existing preclinical methods often fail to accurately predict human cardiotoxicity.
• A workshop was convened to address gaps in translating preclinical cardiovascular safety data.

Purpose of the Study:

• To summarize discussions on improving cardiotoxicity assessment in drug development.
• To identify challenges and propose solutions for preclinical cardiovascular safety evaluation.
• To outline the need for human-relevant platforms in drug safety testing.

Main Methods:

• White paper summarizing a workshop with experts from academia, industry, and government.
• Discussion focused on current gaps and challenges in preclinical cardiovascular safety assessment.
• Exploration of human-derived cardiomyocytes and other human-relevant platforms.

Main Results:

• Urgent need identified to integrate human-relevant platforms into drug development.
• Human-derived cardiomyocytes show potential for regulatory applications.
• Gaps and barriers in preclinical cardiovascular safety assessment were highlighted.

Conclusions:

• Integrating human-relevant platforms is essential to reduce cardiovascular safety liabilities of new drugs.
• Future work should focus on developing and validating these platforms for cardiotoxicity assessment.
• This paper initiates a collaborative effort for human-relevant cardiotoxicity tools, especially for contractile dysfunction and structural injury.