Examples of FDA approvals despite a failed primary endpoint

Understand the conditions that might lead to FDA approval despite a failed primary endpoint


Precedent research is like finding a needle in a haystack. (1) Manually, it is challenging to search through the FDA review packages published through Drugs@FDA or others to identify failed primary endpoints. (2) Existing search tools rely on keyword search options that might or might not identify the relevant information depending on how unique the keywords are (3) Google will return results from recent publications but will not search through the review packages to identify examples (4) ChatGPT will return a generalized answer that is not well referenced and is disconnected from the context of the source document

Features Used

  • Intelligent Search
  • Result Verification


Formulate your question in natural language and use Cedience's intelligent search to get a reference-backed answer
In this example, the question used is:

- Are there any examples of FDA approval despite a failed primary endpoint?


Apply the following filters filters to search all FDA review packages (1) Agency > FDA (2) Document Category > Review Packages


Enter your question or request in the intelligent search field and click Search


Review the answer and provided references


Here's the answer Cedience's intelligent search returns:

Carvedilol, a beta-blocker used to treat high blood pressure and heart failure, was approved based on a secondary endpoint of death, despite failure to meet the primary endpoint. This was accepted based in part on supporting evidence from other drugs of the same class.
In the case of the drug Aricept, the studies in patients with mild to moderate AD failed to show a statistically significant difference between the 5 and 10mg doses on the trial’s measure of global functioning. However, both doses were superior to placebo on the measure, and a 23mg dose of Aricept was approved based on a single 24-week trial that compared that dose to the already marketed 10mg dose in patients with moderate to severe AD.
In the case of the drug QVAR, despite one failed adult study and one failed pediatric study, the FDA considered two successful adult studies as substantial evidence for approval. This was further supported by the fact that the failed adult study lacked assay sensitivity from the fact that active control of approved drug also failed.
In the case of the drug Gleevec, the FDA approved the drug based on the CAPRICORN Study, which had a nominally significant effect on survival (p=0.03) despite failing its primary endpoint. This was accepted based on other pertinent information.
In the case of the drug Stivarga, the FDA agreed that the planned subgroup analyses were acceptable, but noted that the trial must be successful in its overall primary efficacy endpoint for any subgroup analyses to be meaningful.