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IDMC SAYS "CONTINUE"!

|About: CEL-SCI Corporation (CVM)
Summary

On 10/15/19, the CEL-SCI Announced that the IDMC recommnded the trial to Continue.

IDMC had ALL of the Unblinded data and 96% of the Events.

Event-Driven Studies MUST continue to endpoint for trial to stop.

They could have stopped the trial for Futility!

About CEL-SCI

CEL-SCI Corporation (CVM) is a small-cap (~$300 million), clinical-stage cancer bio-pharmaceutical company. Multikine, a cocktail combination of cytokines and chemokines, is a prospective neoadjuvant treatment and an investigational drug candidate in clinical development for newly diagnosed advanced primary head and neck cancer. It has also received orphan status.

The goal of treatment with Multikine is to boost the body's immune system prior to standard of care. The Phase III study is fully enrolled with 928 patients, and the last patient was treated in September 2016.

IDMC NEWS 

On October 15, 2019, CEL-SCI announced that the October meeting of the IDMC had occurred.  In the Press Release it said a few things: 

  • At the most recent IDMC meeting in October 2019 the IDMC reviewed “progression free and overall survival and limited demographic and safety data available for the aforementioned protocol.”
  • The IDMC recommendation “is to continue the trial until the appropriate number of events has occurred”.

With 96% of the events occurring, the IDMC could have determined that the Trial was FUTILE..but they didn't

Why Hasn't It Been Stopped For Futility?

However, why hasn't the IDMC recommended to shut the trial down for "futility". Before we answer that, let's go over what "futility" means.

The term "futility" is used to refer to the inability of a clinical trial to achieve its objectives. In particular, stopping a clinical trial when the interim results suggest that it is unlikely to achieve statistical significance can save resources that could be used on more promising research.

The Phase III trial endpoints are clear: The Gold-Standard of Overall Survival.

The Multikine trial nears its ninth year. The IDMC has met multiple times and as recently as October 2019. At each of these meetings, the IDMC could have made the recommendation to end the trial early for futility...but they haven't.

Don't think for a second that the IDMC doesn't shut trials down for futility. They do it often. Just look at a few this year:

But why won't any of the Bears answer this fundamental question: "Why hasn't the IDMC shut the trial down early due to futility?" We know why...it doesn't fit their narrative.

Why Hasn't It Been Stopped Early for Positive Efficacy

If Multikine is the wonder drug we all think, the blogger states it would have been stopped early for positive efficacy. Or would it?

As we previously wrote, this is a Event-Driven study...not a Time-Driven like other neoadjuvant clinical trials. Big difference!

Only a small percentage of trials are stopped early for "benefit." This is because stopping trials early for benefit skews the data and gives a "biased" impression of effectiveness which automatically tarnishes potentially positive results. The IDMC must also consider whether or not the trial findings will change clinical practice.

If the IDMC review were to recommend an early stoppage and the recommendation was implemented by CEL-SCI, it would make it more difficult to provide the exact efficacy of Multikine. It would also open up the possibility for biased "False-Positive" data results. At this stage in the trial, with the understanding of the "delayed clinical effect," it would be imprudent to jeopardize the results.

The IDMC may have already observed that the unblinded interim data is indicating greater benefits to the Multikine treated group vs. the Standard of Care group. However, if the IDMC recommends early unblinding and termination of the study based on the available interim data, they will be doing so before the predetermined stopping boundary of 298 events is crossed.

Remember, this is an EVENT DRIVEN study and THEREFORE must reach the last event of 298 to determine statistical significance!

Two Important Slides from CEL-SCI's Corporate Presentation

Slide 26

ss Slide 27

sss Full Presentation HERE

The Blogger Speaks

af Of course the Poly Sci major that blogs had to comment.

Said that the word "recommendation" isnt in quotes....Wow...just wow

But a subsequent 8-K filing said this:

aa

We call bullshit on this desperate blogger.

Chart Analysis

From a technical point of view, the last time IDMC recommended the trial to continue (March 2019), the chart was showing a similar pattern and the PPS went from $3 to $9 in 6 Months.

chart We expect a material rise in the PPS in the coming WEEKS!

Where we are today

The average weighted time since treatment from this trial is 4.4 years. A rough calculation makes the average survival of this whole group to be around 40% according to this SEER data and number of events should be around 60% in the two comparator arms.

60% from 672 equals 403. There should be at least 400 deaths or at least 200 in the Standard of Care arm. This leaves 98 events in the Multikine arm. We see clearly that either Multikine is a miracle drug or something is overly pessimistic on the survival assumptions.

Some, but not all, studies show higher survival in clinical trials than expected in real life (Pancreatic cancer: Survival in clinical trials versus the real world.). So we assume that survival is better than expected in the public database.

We think that our assumptions shown in this survival analysis might be closer to reality or at least show the most optimistic possible outcome for the patient of this clinical trial: Stage III cancer survival data being considered (a near 50% survival at year 5), a credible level of dropouts (11%) and an endpoint reached by December.

This still implies a 28% survival benefit on the test arm vs. control arm

Stats

CVM Clinical Trial Survival Analysis by Fosco

  1. Efficacy (Overall Survival Improvement from Test arm VS SoC ) is now shown to be of 26%
  2. Theoretical end date for the trial (298th event) is estimated for January 5, 2020

Most importantly, the Ergomed publication confirms, in the most striking manner, the previous predictions of our model :

  • 298th event was predicted long ago by us to be ending at least by Q4 2019.
  • Multikine is predicted to be a very effective drug against Head and Neck cancer.

CONGRATS TO ALL LONGS

KILLCVMSHORTS.COM

Disclosure: I am/we are long CVM.