From Dr. Bream;
From FB Bream Medical, LLC
I felt compelled to make a statement regarding this given how empassioned I feel about leronlimab and given that I have spoken a good deal about it and other medications that I feel are deserving of an EUA on this page.
The first thing I would say if me, a family member, or close friend were to get critically ill with COVID, leronlimab would still be the drug I would I would request.
The FDA is correct that both the phase 2 mild-moderate and phase 3 severe-critical trials failed of leronlimab failed their primary endpoint. I also agree on the need for leronlimab to have more study based on its phase 3 severe-critical trial that showed benefit in the critically ill subgroup of intubated patients. The company has agreed with that need and set up large phase 3 trials of leronlimab in Brazil where there is still a significant number of severe/critical patients. In fact, there have been no statements to the contrary.
However, I also have multiple disagreements with the FDA’s assertions.
To say that CD-10, the mild-moderate trial, failed to hit its secondary endpoints isn’t correct. With statistical significance, it met the following secondary outcome measure:
Change from baseline in National Early Warning Score 2 (NEWS2) [ Time Frame: Days 3, 7, and 14
This is verifiable on the press release and clinicaltrials.gov
2) The FDA remarks on the need for well-designed clinical trials in this document even though hydroxychloroquine was given EUA based on a very poorly designed study, convalescent plasma was not studied in any RCT prior to EUA, and bamlanivimab was approved based on a phase 2, but ultimately none of the phase 3 endpoints were met.
3) Complety dismissing subgroup analysis for the most critical patients is a mistake, in my opinion. Yes, it needs more study, which is being done. But, one has to question the motivation of issuing this statement when these large scale studies haven’t even begun. It appears that CytoDyn has done what the FDA has asked to gain more data, however, such statements will make it much harder to get patients to enroll in the international trial.
4) The FDA had oversight of these trials. Why didn’t the FDA intervene at any point during the interim analysis? Did the FDA provide different guidance that wasn’t accepted? Did the company want a different trial design than the FDA rejected?
5) Probably most importantly, are we just supposed to think that some of the most brilliant science minds in the world - with impeccable credentials - such as Dr. Otto Yang, Dr. Bruce Patterson, Dr. Harish Seethamraju, Dr. Jay Lalezari - are just wrong? Do we ignore all the subgroup data, eIND data and open-label extension data like it doesn’t exist? Supposedly, the open label extension data is quite impressive. These data shouldn’t count toward approval. But, it shouldn’t be disregarded either.
6) If the FDA truly believed this, since this data has been available for almost 2 months, why has it continued to allow open-label extension? What has happened to the patients in Phillippines who received leronlimab via compassionate special permit? If the drug has no potential, why is India inquiring about it?
My thesis that based on the subgroup data, the eIND data, and the reported open-label extension data, that leronlimab deserves an EUA while it proves itself in a larger trial remains unchanged.
Ultimately, science always prevails!
From FB Bream Medical, LLC
I felt compelled to make a statement regarding this given how empassioned I feel about leronlimab and given that I have spoken a good deal about it and other medications that I feel are deserving of an EUA on this page.
The first thing I would say if me, a family member, or close friend were to get critically ill with COVID, leronlimab would still be the drug I would I would request.
The FDA is correct that both the phase 2 mild-moderate and phase 3 severe-critical trials failed of leronlimab failed their primary endpoint. I also agree on the need for leronlimab to have more study based on its phase 3 severe-critical trial that showed benefit in the critically ill subgroup of intubated patients. The company has agreed with that need and set up large phase 3 trials of leronlimab in Brazil where there is still a significant number of severe/critical patients. In fact, there have been no statements to the contrary.
However, I also have multiple disagreements with the FDA’s assertions.
To say that CD-10, the mild-moderate trial, failed to hit its secondary endpoints isn’t correct. With statistical significance, it met the following secondary outcome measure:
Change from baseline in National Early Warning Score 2 (NEWS2) [ Time Frame: Days 3, 7, and 14
This is verifiable on the press release and clinicaltrials.gov
2) The FDA remarks on the need for well-designed clinical trials in this document even though hydroxychloroquine was given EUA based on a very poorly designed study, convalescent plasma was not studied in any RCT prior to EUA, and bamlanivimab was approved based on a phase 2, but ultimately none of the phase 3 endpoints were met.
3) Complety dismissing subgroup analysis for the most critical patients is a mistake, in my opinion. Yes, it needs more study, which is being done. But, one has to question the motivation of issuing this statement when these large scale studies haven’t even begun. It appears that CytoDyn has done what the FDA has asked to gain more data, however, such statements will make it much harder to get patients to enroll in the international trial.
4) The FDA had oversight of these trials. Why didn’t the FDA intervene at any point during the interim analysis? Did the FDA provide different guidance that wasn’t accepted? Did the company want a different trial design than the FDA rejected?
5) Probably most importantly, are we just supposed to think that some of the most brilliant science minds in the world - with impeccable credentials - such as Dr. Otto Yang, Dr. Bruce Patterson, Dr. Harish Seethamraju, Dr. Jay Lalezari - are just wrong? Do we ignore all the subgroup data, eIND data and open-label extension data like it doesn’t exist? Supposedly, the open label extension data is quite impressive. These data shouldn’t count toward approval. But, it shouldn’t be disregarded either.
6) If the FDA truly believed this, since this data has been available for almost 2 months, why has it continued to allow open-label extension? What has happened to the patients in Phillippines who received leronlimab via compassionate special permit? If the drug has no potential, why is India inquiring about it?
My thesis that based on the subgroup data, the eIND data, and the reported open-label extension data, that leronlimab deserves an EUA while it proves itself in a larger trial remains unchanged.
Ultimately, science always prevails!
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