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Published on: May 7, 2020
Optimizing phase II of drug development for disease-modifying compounds.
1Department of Neurology and Psychiatry, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. jcummings@mednet.ucla.edu
Summary
Drug development faces challenges in Phase II studies. Strategies like biomarkers, population enrichment, and adaptive designs aim to improve efficiency, but require validation for successful clinical trials.
Area of Science:
- Drug Development
- Clinical Trials
- Biomarkers
Background:
- Phase II proof of concept (POC) (IIa) and dose-finding (IIb) studies are critical but challenging in drug development.
- Prolonged timelines delay patient access to therapies and impact market entry.
- Current alternative outcomes like imaging and fluid biomarkers are not yet validated.
Purpose of the Study:
- To explore strategies for improving the efficiency and success rate of Phase II drug development studies.
- To address the central question of determining sufficient evidence for Phase III progression.
- To reform Phase II studies for faster and more reliable drug development.
Main Methods:
- Investigating the use of validated biomarkers (e.g., MRI, CSF tau/amyloid beta, PET) as alternative endpoints.
- Examining population enrichment strategies to accelerate milestone achievement.
- Considering adaptive dose-response designs for seamless Phase IIb to Phase III transition.
Main Results:
- No single strategy has been fully validated in successful drug development programs.
- Biomarkers, population enrichment, and adaptive designs show promise but require further validation.
- The optimal amount of information needed to proceed to Phase III without excessive risk remains a key challenge.
Conclusions:
- Reforming Phase II studies is essential for efficient drug development.
- Validated biomarkers, targeted populations, and adaptive designs offer potential solutions.
- Further research and validation are needed to optimize Phase II study designs and reduce failure risks.
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