Cytodyn Inc (CYDY)

[CTMedic]

It is now 26 days since the completion of CD12 (remember Novartis took 61 days for data from the con-Covid trial readout).

While we wait for CD12 results, let’s examine the known data.

Which data you ask?

The 50%/195 interim data.

That data is blinded, you say?

Why yes it is, but not from the DSMB.

As a review, what are the responsibilities of the DSMB?

."Assessing the legal duty to use or disclose Interim data for ongoing Clinical Trials." Pages 51-84
---Journal of Law and the Bisciences.Pub. 13 August 2019 by Lisa Eckstein
DSMB Stopping Rules:
Stopping for Efficacy
Stopping for Inferiority
Stopping for Futility
Stopping for safety

Ok, bear with me here as we conduct a logical thought experiment.

By the way, I really would like to hear exactly where my logic fails, not a simple rejection of my conclusions. Thanks in advance.

Let’s go!

So we know that the trial was not stopped after the second interim review.

“DSMC recommends CytoDyn continue the study as planned, with the protocol defined sample size and power to achieve the primary endpoint”

https://www.cytodyn.com/investors/news-events/press-releases/detail/477/cytodyn-receives-positive-dsmc-recommendation-after-interim

How was this decision reached?

The DSMB reviewed the available data and determined that the trial was likely to be successful continuing under trial conditions.
Please remember that the DSMB membership includes:

“at a minimum:
• Expert(s) in the clinical aspects of the disease/patient population being studied;
• One or more biostatisticians; and,
• Investigators with expertise in current clinical trials conduct and methodology.”
•
https://www.nidcr.nih.gov/research/human-subjects-research/toolkit-and-education-materials/interventional-studies/data-and-safety-monitoring-board-guidelines#i-roles-and-responsibilities

The claims that the DSMB would not have enough data at interim analysis are simply not true.

Cytodyn CD12 trial primary endpoint is mortality.

Interim analysis evaluated number of patients alive or dead in each arm.

To state that there is not enough data to make a determination of trial continuation, modification or termination therefore assumes that investigators were not aware of which patients were alive and which were dead.

I am certain it was known who had died.

Now we will address the contested issue of mortality and the futility of CD12, based on the imposition of a 28% mortality rate upon the trial population.

Let us assume that the population of severe and critical patients from which the CD12 patients were chosen in fact had a 28% mortality rate.

We know that there were 45 deaths at the interim analysis.

Therefore, placebo arm would have had 18 deaths (0.28 x 195/3)

The remaining deaths would have had to occurred in the leronlimab/treatment arm.
45-18 = 27 treatment arm deaths.

What was the reduction in mortality at the interim review IF the mortality was 28% in the severe/critical population from which trial participants were selected?

Leronlimab/treatment arm 27/130= 0.208 or 20.8% mortality

Placebo we are told 28% mortality

What is the improvement in the treatment arm?

(28-20.8)/28= 25.7% reduction in mortality

p=0.296. Uh oh.

Would doubling the number of trial participants (expectation at trial completion) be sufficient?

No. Cytodyn would have had to add more than 50% to the final trial population to achieve statistical significance (as was the case for Humanigen’s lenzilumb trial)

This brings us back to the DSMB.

Again, what are the expected actions of the DSMB in response to data indicating the trial will fail to meet its endpoint?

Modify or terminate the trial.

Was the trial terminated for utility or trial size modified?

No it was not.

Ergo, the premise upon which this exercise was built, that the offered 28% mortality is representative of the CD12 trial population and that the trial is due to fail, must be false.

Patience.