CYDY may be positioned to seek accelerated approva
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Posted On: 03/23/2025 7:02:25 PM
CYDY may be positioned to seek accelerated approval for mTNC using compelling data.
In again reviewing Dr Jay's shareholder letter and related info, I took particular note of his observation that oncology holds "the highest potential and shortest timeline for return on investment in the form of a partnership or drug approval." He also announced that CYDY is forming an oncology centered Advisory Board and that CYDY would "continue discussions with KOLs (key opinion leaders) about the possibility of initiating a follow up study on patients with mTNBC ... on currently available data."
The standard upon which the FDA issues accelerated drug approval requires establishing a surrogate endpoint from a clinical trial to predict clinical benefit, with a strong indication that the drug will address an unmet medical need for a life threatening illness. Previously, the FDA has granted accelerated approval for Trodelvy and Keyruda in mTNBC. But some mTNBC patients continue to have needs that neither Trodelvy nor Keytruda can meet.
Think about what we know regarding the Leronlimab mTNBC clinical trial data that will be presented at ESMO in mid May --- a sub group of the 28 patients who completed the trial in 2021 are still alive and cancer free. As fantastic is that news is, the updated LL overall survival(OS) and progression free survival (PFS from those 28 patients may or may not be good enough to surpass the 21 month OS and 9.7 month PFS ultimately established by Keytruda. But, in any case, OS and PFS are typically primary end points, not accelerated approval surrogate endpoints.
Fortuitously, according to the June 2, 2022 issue of The Journal of Clinical Oncology, CYDY, in its mTNBC clinical trial, was using the patients' blood to track decreases in circulating tumor cells after receiving LL "as an exploratory biomarker ... in predicting efficacy." ( While the FDA has apparently never formally recognized decreases in circulating tumor cells as a qualifying surrogate endpoint for accelerated approval purposes, it has recognized the possibility that circulating blood DNA may qualify.) Ultimately, it turned out that 75% (21 of 28) of the LL patients experienced significant decreases in their circulating tumor cells. Consequently, CYDY may be well situated to show that its circulating tumor cell biomarker, used as a surrogate endpoint, is a very accurate predictor of clinical benefit (efficacy), in terms of substantially increased OS and PFS, for the 21 patients who were responders to this surrogate endpoint.
FDA provisions allow the agency to rely on guidance from experts outside the agency in their accelerated approval determinations and accelerated approval also requires a follow up "study" to confirm efficacy. It would appear that CYDY is well aware of those provisions, and is ready to proceed accordingly.
Clearly, if CYDY were to seek accelerated approval in mTNBC based on its 2021 clinical trial, it would be relying on a retrospective analysis, and the FDA might reject it as untimely or on some other technical basis, But the FDA will soon have a new Commissioner, and if his goal is to save lives, he may just find the Leronlimab circulating blood cell data very compelling.
In again reviewing Dr Jay's shareholder letter and related info, I took particular note of his observation that oncology holds "the highest potential and shortest timeline for return on investment in the form of a partnership or drug approval." He also announced that CYDY is forming an oncology centered Advisory Board and that CYDY would "continue discussions with KOLs (key opinion leaders) about the possibility of initiating a follow up study on patients with mTNBC ... on currently available data."
The standard upon which the FDA issues accelerated drug approval requires establishing a surrogate endpoint from a clinical trial to predict clinical benefit, with a strong indication that the drug will address an unmet medical need for a life threatening illness. Previously, the FDA has granted accelerated approval for Trodelvy and Keyruda in mTNBC. But some mTNBC patients continue to have needs that neither Trodelvy nor Keytruda can meet.
Think about what we know regarding the Leronlimab mTNBC clinical trial data that will be presented at ESMO in mid May --- a sub group of the 28 patients who completed the trial in 2021 are still alive and cancer free. As fantastic is that news is, the updated LL overall survival(OS) and progression free survival (PFS from those 28 patients may or may not be good enough to surpass the 21 month OS and 9.7 month PFS ultimately established by Keytruda. But, in any case, OS and PFS are typically primary end points, not accelerated approval surrogate endpoints.
Fortuitously, according to the June 2, 2022 issue of The Journal of Clinical Oncology, CYDY, in its mTNBC clinical trial, was using the patients' blood to track decreases in circulating tumor cells after receiving LL "as an exploratory biomarker ... in predicting efficacy." ( While the FDA has apparently never formally recognized decreases in circulating tumor cells as a qualifying surrogate endpoint for accelerated approval purposes, it has recognized the possibility that circulating blood DNA may qualify.) Ultimately, it turned out that 75% (21 of 28) of the LL patients experienced significant decreases in their circulating tumor cells. Consequently, CYDY may be well situated to show that its circulating tumor cell biomarker, used as a surrogate endpoint, is a very accurate predictor of clinical benefit (efficacy), in terms of substantially increased OS and PFS, for the 21 patients who were responders to this surrogate endpoint.
FDA provisions allow the agency to rely on guidance from experts outside the agency in their accelerated approval determinations and accelerated approval also requires a follow up "study" to confirm efficacy. It would appear that CYDY is well aware of those provisions, and is ready to proceed accordingly.
Clearly, if CYDY were to seek accelerated approval in mTNBC based on its 2021 clinical trial, it would be relying on a retrospective analysis, and the FDA might reject it as untimely or on some other technical basis, But the FDA will soon have a new Commissioner, and if his goal is to save lives, he may just find the Leronlimab circulating blood cell data very compelling.
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