Sharing a high quality and thoughtful post from YM
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Posted On: 01/03/2021 3:51:18 PM
Sharing a high quality and thoughtful post from YMB:
After another few months of following this board, I am once again sharing my perspective as a regulatory professional who has filed eINDs for antiviral monoclonal antibodies during a previous public health emergency.
In my view, the granting of an open label expansion for the CD12 trial is a clear signal that FDA sees a favorable risk/reward basis for continued use of Leronlimab. As some have pointed out, there is still a possibility that the trial may not meet its endpoint on a statistical basis, and it is true that there are examples of drugs which were granted open-label extensions without going on to be approved. However, the explicit purpose of having a study with DSMC interim reviews is to close a trial as soon as it becomes clear that there will be a statistical failure; as we know, the DSMC interim recommendations for CD12 have all been positive and most recently indicated that the statistical threshold may be met before full enrollment, which has been achieved at this point regardless.
I’ve also spent some time thinking about the additional criteria FDA specified to allow continued eIND use of Leronlimab outside of the new open label arm for CD12, which equates to more restrictive PEEP/PaO2 thresholds that will effectively exclude less severe patients from receiving the drug outside of CD12 trial sites. In my past experience with emergency use, FDA’s position was that eIND data is the least reliable/interpretable data and that companies should avoid using eINDs if at all possible. Data collected under a protocol such as CD12 is much higher quality and allows all parties (FDA, the drug company, the doctors, etc) to make informed decisions based on the results; in contrast, eIND data is uncontrolled and is collected by medical staff who may not be trained for/experienced with the investigational product, often using different standards of care and outcome collection procedures for each individual eIND patient. Therefore, an explanation for why FDA has advised Cytodyn to exclude all but the most severely ill patients from further eIND use may be because data collected for less severe patients outside of the CD12 protocol is likely to be uninterpretable, but the drug may still provide benefit to these people who currently have no other treatment options.
There are some other posters that have covered this in detail, and I’ve seen some compelling points why this might be a positive sign; on the flip side, nothing in from my own experience or on this board has convinced me that this could be a negative development. However, all we can do is speculate until we hear more from Cytodyn or FDA.
After another few months of following this board, I am once again sharing my perspective as a regulatory professional who has filed eINDs for antiviral monoclonal antibodies during a previous public health emergency.
In my view, the granting of an open label expansion for the CD12 trial is a clear signal that FDA sees a favorable risk/reward basis for continued use of Leronlimab. As some have pointed out, there is still a possibility that the trial may not meet its endpoint on a statistical basis, and it is true that there are examples of drugs which were granted open-label extensions without going on to be approved. However, the explicit purpose of having a study with DSMC interim reviews is to close a trial as soon as it becomes clear that there will be a statistical failure; as we know, the DSMC interim recommendations for CD12 have all been positive and most recently indicated that the statistical threshold may be met before full enrollment, which has been achieved at this point regardless.
I’ve also spent some time thinking about the additional criteria FDA specified to allow continued eIND use of Leronlimab outside of the new open label arm for CD12, which equates to more restrictive PEEP/PaO2 thresholds that will effectively exclude less severe patients from receiving the drug outside of CD12 trial sites. In my past experience with emergency use, FDA’s position was that eIND data is the least reliable/interpretable data and that companies should avoid using eINDs if at all possible. Data collected under a protocol such as CD12 is much higher quality and allows all parties (FDA, the drug company, the doctors, etc) to make informed decisions based on the results; in contrast, eIND data is uncontrolled and is collected by medical staff who may not be trained for/experienced with the investigational product, often using different standards of care and outcome collection procedures for each individual eIND patient. Therefore, an explanation for why FDA has advised Cytodyn to exclude all but the most severely ill patients from further eIND use may be because data collected for less severe patients outside of the CD12 protocol is likely to be uninterpretable, but the drug may still provide benefit to these people who currently have no other treatment options.
There are some other posters that have covered this in detail, and I’ve seen some compelling points why this might be a positive sign; on the flip side, nothing in from my own experience or on this board has convinced me that this could be a negative development. However, all we can do is speculate until we hear more from Cytodyn or FDA.
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