Phase 3 trial terminations are rising, and strategic decisions now outpace scientific causes.

A new study in Nature Reviews Drug Discovery analyzes 3,180 terminated Phase 2 and Phase 3 trials (2013–2023). The authors find that late-stage terminations doubled over the past decade, while operational and safety issues stayed relatively stable.

The analysis was conducted using EpistemicGPT and the Epistemic Knowledge Graph to map trial outcomes and termination reasons at scale. The biggest shift is the rise of strategic and business drivers—portfolio reprioritization, M&A, and commercial strategy—now the most frequent causes of late‑stage termination. The pattern suggests that organizations are ending programs for business alignment rather than new scientific evidence.

Key takeaways

• Late‑stage (Phase 2/3) terminations doubled from ~11% to ~22% across the decade.
• Strategic and business factors now outpace clinical efficacy as termination drivers.
• Earlier decision points could reduce sunk costs in Phase 3 development.

Why it matters

Phase 3 trials are costly and slow. Understanding why programs end can help teams rebalance resources earlier, reduce late‑stage losses, and align development plans with real‑world business constraints.

Read the full paper: Bowling, H., Cocucci, A., Koo, D. C. E., & Harrison, R. K. (2025). Analysis of phase II and phase III clinical trial terminations from 2013 to 2023. Nature Reviews Drug Discovery.

FAQ

Q: Why are Phase 3 terminations increasing?
A: Driven primarily by business strategy (portfolio shifts/market changes) rather than drug performance.

Q: What is the financial impact?
A: Lost investments often exceeding $50M–$500M per asset.