The U.S. Food and Drug Administration (FDA) has published a draft guidance document for its Accelerated Approval Program, designed to expedite the approval process for new drugs. The guidance outlines criteria for two types of endpoints considered for accelerated approval: surrogate and clinical endpoints.
Drugs approved under the Accelerated Approval Program must undergo additional confirmatory trials post-approval to secure full approval. These trials are intended to verify and describe the drug’s clinical benefits.
Key Endpoint Definitions
- Surrogate Endpoints
- Defined as a biomarker (e.g., lab measurement, radiographic image, physical sign, or other indicators) that is reasonably likely to predict clinical benefit but is not a direct measure of clinical benefit.
- Example: Conversion of a positive sputum smear to negative during tuberculosis treatment, which is considered reasonably predictive of clinical benefit.
- Clinical Endpoints
- These are measurable outcomes occurring earlier than irreversible morbidity or mortality (IMM) and are reasonably likely to predict an impact on IMM or other clinical benefits.
Additional Endpoint Considerations
- Intermediate Clinical Endpoints
- Defined as therapeutic effects measurable before impacts on IMM. These can support accelerated approval when reasonably likely to predict a drug’s effect on IMM or clinical benefit.
Post-Approval Requirements
- Drugs approved through this pathway must complete post-approval confirmatory trials to substantiate their clinical benefit.
- This ensures that the benefits observed at earlier stages of drug development hold in broader, real-world patient populations.
The updated guidance reflects FDA’s ongoing efforts to refine the balance between early access to potentially life-saving drugs and ensuring their efficacy and safety.
Source: GxP News, December 9, 2024.
