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Late Stage of Drug Development


1st scenario/ Issue
An example of a question/scenario facing a cross functional drug development team to obtain regulatory perspective on choice of primary endpoint for a registration study

In this example, we use one of the big four tumor types, Prostate cancer indication. The team would like to expedite the drug development of a NME targeting prostate cancer.


Question: Would the FDA agree to consider using reduction in PSA response as a primary endpoint in a phase II registration study for a possible accelerated approval in chemotherapy and hormone treatment refractory as well refractory to newly approved drugs for prostate cancer patients?
After thorough analysis, the GRSAOnline Advice might be along these lines:

GRSA Response/Advice: It is unlikely that reduction in PSA scores alone would be sufficient for approval in this patient population and possibly a 'No' to an accelerated approval. We would suggest that other endpoints such as durable pain reduction, as well as PFS with OS as co-primary endpoint be proposed along with a post approval commitment for a Phase III study for a better probability of successful outcome or as a respectable starting point for further negotiations, in reaching agreement with the FDA.

Question: If the primary endpoint, and its method of assessment/determination is solely operator dependent, and at local site level, how would you mitigate the FDA's concern of a potential bias in an open label proposed registration trial?

GRSA Response/Advice: One of the options would be to propose a central third party blinded review of the results to minimize the potential bias in an open label registration trial.

Note: We could also perform an extensive review of the regulatory precedence, and identify as to what conditions there may be other options for to mitigate this issue.