Reducing attrition in drug development: smart loading preclinical safety assessment

Area of Science:

• Drug development
• Toxicology
• Preclinical research

Background:

• The preclinical good laboratory practice (GLP) stage of toxicology testing is a significant investment in drug development.
• Over 20% of potential new medicines fail during this GLP phase due to safety concerns.
• Historical data indicates that over 50% of these failures are linked to target organ toxicities or cardiovascular risks.

Purpose of the Study:

• To reduce the high attrition rates in the preclinical GLP toxicology phase.
• To identify key safety concerns that lead to drug candidate failure.
• To propose a strategy for improving drug pipeline quality and reducing R&D costs.

Main Methods:

• Analysis of historical 'stopping toxicities' in drug development.
• Identification of common reasons for failure, specifically target organ toxicities and cardiovascular risks.
• Proposal for frontloading 2-week repeat-dose toxicity studies and comprehensive cardiovascular safety assessments.

Main Results:

• Over 50% of drug development failures in the GLP phase are linked to target organ toxicities or acute cardiovascular risks.
• Implementing early toxicity and cardiovascular assessments can potentially reduce attrition by 50% in the GLP phase.
• This approach is expected to decrease overall animal usage and R&D expenditures.

Conclusions:

• Early identification and mitigation of target organ toxicities and cardiovascular risks are crucial for successful drug development.
• Frontloading specific toxicity studies can significantly improve the efficiency and success rate of the preclinical GLP phase.
• Optimizing preclinical safety assessments enhances drug pipeline quality, reduces costs, and minimizes animal testing.