dfw: ohm responded to your query just as I was about to respond. Needless to say, I am not about to take issue with ohm regarding the appropriate way to understand the significance of a decrease in circulating tumor cells for a mTNBC patient, but perhaps I can distinguish (legal term) his assessment that the FDA would not consider a decrease in CTCs as "definitive proof of effect even with metastasis" for purposes of understanding the difference between the FDA's rules for evaluating accelerated vs permanent approval.
My reading of the pertinent FDA rules is that accelerated approval hinges on the FDA using a surrogate endpoint, which can be a biomarker or radiologic image, to predict a clinical benefit (for a life threatening condition with an unmet medical need), but which is not a sign of clinical benefit itself. Also, in researching its pronouncements relating to suitable predictive
surrogate endpoints, I found, for example, that the FDA cites reduction in fever or HDL in the blood as beneficial, but not predictive of stabilizing cancer or preventing heart attacks, and therefore not suitable as surrogate endpoints.
For accelerated approval, the FDA has to find that there is a reliably predictive relationship between the surrogate endpoint and the targeted clinical benefit. That prompted me to ask Google artificial intelligence (Gemini) if the FDA has ever recognized CTCs as an acceptable surrogate endpoint. I paraphrased Gemini's answer, as set forth in the quoted portion of your post, regarding the FDA's potential consideration of circulating blood DNA as a suitable surrogate endpoint. And although I was very fortunate in college to scrape out a C in a bonehead physics course ( thanks only to a kindly professor who was a fan of our football team), it would seem very likely to scientific bonehead me that a verified decrease in CTCs would reliably predict shrinking or disappearing tumors. Moreover, I surmise that CYDY will reveal at ESMO that the CTC decreases demonstrated in 2021 during its Leronlimab clinical trial did exactly that.
My reading of the pertinent FDA rules is that accelerated approval hinges on the FDA using a surrogate endpoint, which can be a biomarker or radiologic image, to predict a clinical benefit (for a life threatening condition with an unmet medical need), but which is not a sign of clinical benefit itself. Also, in researching its pronouncements relating to suitable predictive
surrogate endpoints, I found, for example, that the FDA cites reduction in fever or HDL in the blood as beneficial, but not predictive of stabilizing cancer or preventing heart attacks, and therefore not suitable as surrogate endpoints.
For accelerated approval, the FDA has to find that there is a reliably predictive relationship between the surrogate endpoint and the targeted clinical benefit. That prompted me to ask Google artificial intelligence (Gemini) if the FDA has ever recognized CTCs as an acceptable surrogate endpoint. I paraphrased Gemini's answer, as set forth in the quoted portion of your post, regarding the FDA's potential consideration of circulating blood DNA as a suitable surrogate endpoint. And although I was very fortunate in college to scrape out a C in a bonehead physics course ( thanks only to a kindly professor who was a fan of our football team), it would seem very likely to scientific bonehead me that a verified decrease in CTCs would reliably predict shrinking or disappearing tumors. Moreover, I surmise that CYDY will reveal at ESMO that the CTC decreases demonstrated in 2021 during its Leronlimab clinical trial did exactly that.
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