Cytodyn Inc (CYDY)

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A couple of other references to some related issues:

In this tweet of Dr. Patterson,

I used 3-4 doses on EIND patients so I was not the one choosing 2! https://t.co/R5WzOtVOeg

— Bruce K. Patterson MD (@brucep13) July 5, 2021

he says that the dosage he used in the eINDs was 3-4. I don't know the number of such patients but lot of the early enthusiasm for LL in Covid came from his positive comments which were based on his observations of anecdotal eINDs for critical patients. One assumes this data was part of Cytodyn's cd12 proposal to the FDA.

However, Dr. Seethamraju says between ~ min 20 and 24

that he treated 11 critical eIND patients with 2 doses. He also says that based on the results he was able to convince the FDA that we should look into the plausibility of this medication etc. (But this may be referring to early discussions before cd12 trial design proposal when they had difference of opinion on dosage.)

If we go with just these two sets of eINDs, there was promising critical-patient data with Cytodyn using both 2 doses and 3-4 doses. Logically, assuming the safety of the drug, we should err on the side of the potential for success and go with the continued dosing especially when we were looking at results at Day 28 and not Day 14. Cytodyn wanted 4 and FDA allowed only 2. Facts.

The caveat to this rationale is that the trial was not simply for critical patients (who I think formed the bulk of our "dramatic" eINDs) but what would be a majority of just severe patients. So, FDA may have argued that 4 doses is not justified for a severe+critical population when there is already good (Dr. Seethamraju's) eIND data for the drug's efficacy with 2 doses for certain critical patients.

And what must that argument come down to? Must be on the safety of 4 doses. We are in a pandemic; people are dying left and right. Here is a drug that is giving significant results in the eINDs warranting a phase 3 trial. The trial endpoint is assessed at Day 28; the doctors want the Drug dosing till Day 21. Why would we (FDA) stop it at Day 7?

Must come down to: What if the drug is not safe and we are risking the health of patients by giving them more than 2 doses? The given data from eINDs support both 3-4 and 2 doses but not enough to suggest 4 will work in cases 2 does not. (Perhaps) We are more convinced by Dr. Seethamraju's eINDs than Dr. Patterson's, so we will not take the safety risk of 4 doses or allow more than what was used in the (Seethamraju) eINDs that we have decided to prioritize. 2 should suffice to check the efficacy.

And from what I understand, only if FDA had argued on safety of 4 doses vs 2 can we entertain the question of doing a Phase 1 trial on severe/critical patients in order to check drug tolerance etc. It cannot be: "We are ok on the safety of 4 doses. However your data (the part that we consider to be primary) is done with 2 doses only, therefore we will only allow 2 doses." In the latter argument, are we supposed to go do a Phase 1 trial to show superiority of 4 over 2 doses in severe-critical patients? That seems nonsensical.

Of course, from our standpoint, safety is already established. We don't have input to suggest FDA said otherwise and questioned safety of 4 doses. More likely, it seems FDA must have decided to prioritize the eINDs of Seethamraju which used only 2 doses and so a trial based on that data can only have 2 doses. And they will not allow more whether safe or not, whether or not the Cytodyn doctors at that stage and based on their greater experience with the drug are seeking 4 doses.

ALL that said, I am fine with the way things are working out. cd12 is step 1 like a phase 2 and Brazil is the Main that will prove one way or other for LL in this indication.