Cytodynamite, A belated answer. Have been some

Cytodynamite,

A belated answer. Have been somewhat busy lately. Most of info below from:

https://www.fda.gov/patients/fast-track-break...gh-therapy

"Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).

To determine whether the improvement over available therapy is substantial is a matter of judgment and depends on both the magnitude of the treatment effect, which could include duration of the effect, and the importance of the observed clinical outcome. In general, the preliminary clinical evidence should show a clear advantage over available therapy.

For purposes of Breakthrough Therapy designation, clinically significant endpoint generally refers to an endpoint that measures an effect on irreversible morbidity or mortality (IMM) or on symptoms that represent serious consequences of the disease ."

They (FDA) don’t specify a number of patients required, however normally from the statistical viewpoint the minimum number is 20 when the sample space is “normally distributed”. In our case, and, as an example, the questions is: how probable is for 7 patients to have their CTC reduced greatly when they have taken Leronlimab??. In this case the sample space is not normally distributed from the statistical perspective.

So, I believe that a small(er) number of patients is not a big hurdle. The consistency of results is what is important, and, as somebody already suggested, I would not be surprised if the FDA was involved on this:

"Breakthrough Therapy designation is requested by the drug company. If a sponsor has not requested breakthrough therapy designation, FDA may suggest that the sponsor consider submitting a request if:
(1) after reviewing submitted data and information (including preliminary clinical evidence) , the Agency thinks the drug development program may meet the criteria for Breakthrough Therapy designation and,
(2) the remaining drug development program can benefit from the designation."

An interesting video about the qualifying criteria including the experience with Keytruda (the first product under BTD) can be found here (more than an hour duration but worth watching).

https://www.brookings.edu/events/breakthrough...-criteria/

Data from patients # and #4 will be CRITICAL . I am not expecting zero CTC count, but a very large reduction from initial values. This will have a earthquake-like impact on the company.