FDA Signals New Era: Certain Drugs May Win Approval After a Single Clinical Trial
The FDA is once again reshaping the regulatory landscape—this time by opening the door for some therapeutics to be approved based on one adequate and well-controlled clinical trial, supported by confirmatory evidence, rather than the traditional requirement of two trials. While this pathway has existed in statute for years, recent FDA communication and regulatory decisions signal a renewed willingness to apply it more broadly—especially in serious or life-threatening diseases with high unmet medical need.
What Does This Mean?
For sponsors, this shift could dramatically change development timelines, resource allocation, and market strategy. A well-designed pivotal study—paired with robust supportive data—may now be sufficient to reach the finish line for certain products. But with this opportunity comes responsibility: the “one-trial approval” standard does not mean reduced scrutiny. Quite the opposite.
The FDA expects:
Exceptional statistical rigor, including strong control of Type I error
Highly persuasive clinical outcomes, typically with large effect sizes
Well-understood mechanisms of action supported by translational and biomarker data
Consistency across subgroups, sensitivity analyses, and secondary endpoints
Manufacturing and CMC maturity suitable for commercial launch
Where the FDA Is Applying This Approach
Recent cases span oncology, rare diseases, infectious diseases, and advanced therapeutics. The agency has emphasized that each application is program-specific, but the common thread is clear, compelling evidence of benefit that regulators judge unlikely to be due to chance or bias.
Examples include:
Breakthrough-designated therapies with dramatic clinical effects
Rare-disease programs with strong natural-history data
Therapies with well-validated surrogate endpoints
Programs demonstrating both clinical and biological plausibility
This aligns with Congressional intent dating back to the FDA Modernization Act, which explicitly allowed single-study approvals in appropriate circumstances.
Implications for Sponsors and Developers
This evolving stance offers a strategic opportunity—but also a warning. Sponsors aiming for a single-study approval should plan early, beginning with robust Pre-IND and end-of-phase discussions, and align tightly with FDA expectations around:
Endpoint selection (clinical or validated surrogate)
Statistical design and powering
CMC readiness and comparability
Real-world data or natural-history studies as confirmatory evidence
Post-marketing commitments, if required
Programs without a crisp regulatory story—or with avoidable design flaws—are unlikely to benefit.
Bottom Line
The FDA’s renewed openness to approving drugs based on a single pivotal trial is a meaningful shift for the industry. For sponsors prepared with strong science, rigorous execution, and proactive regulatory engagement, this pathway may accelerate access to transformative therapies.
Whether this becomes a broader trend will depend on future approvals, policy updates, and how effectively companies leverage the opportunity.
