More likely, the staff in charge of enrolling the trial are taking off for holiday vacation as was the case during the summer which Gil already explained. Nevertheless, hopefully this lag will give Gil some time to catch his breath and really commit to over-enrolling this dangerously low-powered trial. More than completing enrollment, we need patient numbers. If we do not get more patients, we are going to figure out the hard way why numbers matter. I think everyone understands this.
Athersys stroke trial has only limited statistical power, meeting only minimum reqiremnet of a phase 2.
Similar to the AIIMS trial.
Management salary is the priority here.
Stroke recovery based on global test analysis including modified Rankin Scale (mRS), NIHSS, and Barthel Index (BI).
Go to "In the News" on the Athersys website.
It is the second news item listed.
The item is very much on the Athersys website, and with the long standing collaboration with Jerry Silver and Sarah Busch now a Senior Scientist at Athersys, it is misleading indeed.
In fact, there was considerable confusion on the board about this. Rightly so. I removed my incorrect posts upon tracking down the error.
WRONG AGAIN Ohmtaxi!!!
Athersys misled many on this board.
Gil put the following as news on the Athersys website: "Dec 3, 2014 Barrier-Breaking Drug May Lead to Spinal Cord Injury Treatments".
Indeed, while Athersys has affiliation and shares other IP with Jerry Silver, Professor Department of Neurosciences Case Western Reserve University, for spinal cord injury, the 'Unprecedented' spinal cord injury treatment featured in this news item does not involve MultiStem.
The spinal cord injury treatment candidate mentioned is protected by preliminary patent application (61/621,623) which is NOT shared with Athersys.
My cross-reference of the patents was wrong, so I removed my posts as soon as I tracked it down and confirmed that while Jerry and Athersys are on record for sharing IP for spinal injury, the IP mentioned has nothing (zero) to do with this Athersys.
Questions is: Why did they post this news on the Athersys site knowing they share IP and investors may be confused?
While Athersys shares IP and one of the authors on this work (Sarah A. Busch) is now affiliated with Athersys, Athersys has nothing to do with the IP of the news release.
Yet, they put this news item up on their website, creating confusion.
Sarah Busch Senior Scientist, Regenerative Medicine at Athersys, Inc.
COMPOSITIONS AND METHODS FOR INHIBITING THE ACTIVITY OF LAR FAMILY PHOSPHATASES
LANG, Bradley, T. (1014 Fairfield Avenue, Apt. UpCleveland, OH, 44113, US)
CREGG, Jared, M. (2425 Overlook Road, Apt. 8Cleveland, OH, 44106, US)
SILVER, Jerry (31129 Huntington Woods Pkwy, Bay Village, OH, 44140, US)
WANG, Yi-lan (500 W. University Pkwy, Apt. 2SBaltimore, MD, 21210, US)
Ohmtaxi, the AIIMS trial may have worked within the first month:
"We found that at the end of the first month, patients with stem cells showed more improvement compared to the control group. But at the end of the third month and one year, there was no difference," said Kameshwar Prasad, head, Department of Neurology, All India Institute of Medical Sciences (AIIMS), who led the study."
Now factor in that AIIMS used autologous cells from older patients who suffered a stroke as compared to Multistem which is allogeneic cells derived from a young, healthy donor. Second, the AIIMS study used a mean of 280.75 million cells whereas Multistem high dose is 1 billion +. Finally, AIIMS patients were on average 18.5 post stoke. Athersys is enrolling within 24-48 hrs. Big differences here, but the the AIIMS study tells us that the stroke condition is durable.
So, with this in mind, what if Multistem works well within 30 days but bombs after this? Does this mean that the trial failed, or we simply need another dose within the 30 days? 90 days for a single dose may be too much to ask. We need some answers here.
Boys, this is what we might be facing.
A 30 day difference that diminishes to no significance vs. placebo by 60 and 90 days.
This would suggest that more dosing is needed within the 30 day time frame.
So, I ask again: Is a 30 day positive outcome good enough if we fail the 90 day primary outcome timepoint?
Time Frame: 90 days
This is the billion dollar question.
Its so small you can't read it.
Its so #$%$, you can see they take no pride in it.
For the AIIMS study:
"We found that at the end of first month, patients with stem cells showed more improvement compared to the control group. But at the end of third month and one year, there was no difference," said Kameshwar Prasad, head, Department of Neurology, AIIMS, who led the study.
For the MultiStem study: Time Frame: 90 days
We need a second and third dose of MultiStem at month two and three, but they will figure this out in the phase 3, if we can get there.
How so Ohmtaxi?
Most of the cells are caught in the lung, liver, and spleen. Scattered and dispersed, so divide the billion of cells over multiple locations. Then consider efficacy.
A few cells show up in the brain by IV in animal models, but cells in all locations dramatically decline over three days. See Stroke December 2013 vol. 44 no. 12 3463-3472 Figure 3.
The number of cells showing up in the brain, if any, by IV is not likely therapeutic. We are looking at spleen immuno-modulation as a therapy, and it has to happen over three days as the stem cells are broken down and absorbed. Remember, we do not have a second dose regardless of the response or later condition.
Either MultiStem works to contribute to resolving or reducing further brain damage via the spleen, or it does not. If the spleen shakes off the effects of MultiStem, and its immune response flares again, this will not work with one dose.
Does Multistem make it to the brain. No, not even.
It makes it to the spleen though, and the spleen contributes to stroke-induced neurodegeneration. For MultiStem to work there, it must be as effective as removing the spleen from the patient which is what Pennypacker and Offner (Dec 5, 2014) provide as their brief opinion. They suggeset that removing the spleen reduces infarct volume following middle cerebral artery occlusion. Ok....
Athersys and UT Medical School at Houston reported benefit in the spleen for stroke (below), but for the Phase 2 study at hand, is a single dose of MultiStem enough to achieve a measurable outcome difference in stroke scales relative to placebo? Keep in mind, we need some evidence of significance for the FDA to take Athersys seriously.
Given at 24-48 hours following a stroke, Multistem has to shut detrimental inflammation of the spleen down. It has to do this with a single dose, and the spleen cannot become inflammed after this dose because there will be nothing left to stop it from causing damage.
"Conclusion: MultiStem® improves neurological recovery after stroke through mechanisms involving the spleen. Our data suggest that MultiStem® modulates the immunophenotypes of splenocytes and alters their output of inflammatory cytokines, promoting a protective, anti-inflammatory environment. Regulatory T cells may be one of the pivotal sources of IL-10 and other anti-inflammatory mediators to reduce injury and/or enhance recovery in the brain after stroke." Yang et al., (2012) International Stroke Conference Oral Abstracts
Session Title: Experimental Mechanisms and Models Oral Abstracts II
Same patient numbers: 60 get cells, 60 get placebo.
Difference are stem cell age (autologous used in this study...from old donors), stem cells administered median 18.5 days after stroke, and 280.75 million cells delivered.
So, will earlier administration within 24-48 hrs, a billion cells, and cells from a young donor make a difference?
Parasad et al., 2014
"Most strokes happen suddenly, develop quickly and damage the brain within minutes. In rarer cases, a stroke may continue to worsen for several hours to a day or two as a steadily enlarging area of the brain dies (stroke in evolution). In this case, the stroke is usually (although not always) interrupted by somewhat stable periods when the area temporarily stops getting bigger or some improvement occurs."
To demonstrate Multistem efficacy, Athersys needs to have sufficient patient numbers in a trial to be able to show that the rarer cases when stroke continues to worsen for several hours to a day benefit. There is no way to pre-select for these patients, so the trial will have to be extremely large to include enough of patients to be able to observe this.