In 1992, the US Food and Drug Administration (FDA) implemented the accelerated approval process that allowed conditional approval for drugs that treat serious conditions to address an unmet medical need based on a surrogate endpoint. A surrogate endpoint is a marker (i.e., lab measurement, imaging, physical sign or other measure) believed to predict clinical benefit, but is not the targeted measure of clinically meaningful therapeutic effect for the disease. There is uncertainty as to the relation of a surrogate endpoint to clinical benefit, or of the observed clinical benefit to ultimate outcome.
On July 9, 2012, the US Food and Drug Administration Safety Innovation Act (FDASIA) was signed into law, which e xpanded the FDA-accelerated approval for drugs, biologics, or gene therapies to include intermediate clinical endpoints as another acceptable measure for approval. An intermediate clinical endpoint is a therapeutic effect measure considered reasonably likely to predict the clinical benefit. It can be observed that intermediate endpoints for FDA's accelerated approval can include a measure of function and/or symptoms among other clinically relevant data points, which may direct evaluation regarding potential effectiveness more objectively. For example, overall response rate (ORR), objective response rate (ORR), and duration of response (DoR) etc. are typical intermediate endpoints for oncological accelerated approval. Instances of intermediate endpoint measures such as gross motor milestone achievement can be documented for non-oncological FDA accelerated approvals as well. The clinical relevance of these measures addressing potential efficacy may be unlike when the FDA uses hypothetical biological relevance of surrogate endpoints (e.g., such as using biomarkers only).
The FDA indicates the manufacturers of the drugs, biologics, or gene therapies that receive accelerated approval will need to conduct adequate and well-controlled studies to confirm the anticipated clinical benefit.
