Mighty BMRN needed a correction, and a prudent tap on ATHX's shoulder is keeping it real. What we have to look forward to is Chugai's $10 million investment in Athersys making sense when ATHX's training wheels come off. Chugai is either hedging or they like the cohort 2 results and blinded proportions of the current study. We shall see really soon.
Biotech is not the internet.
Generally, biotech's get higher prices based on actual successes and returns.
Then, they have to keep proving themselves against competition.
What people are not looking at are those that did not make it.
MAPC 1/3 the cost and superior to MSC.
-See previous references.
Erlanger is certainly the expert and obviously they are heading up the Multistem trial. The protocol seems to be, do everything to mitigate the clot(s) and then infuse Multistem. I think this is how its going to go down going forward. Basically this is what their doc says in the video.
He directly says patients may have received tissue plasminogen activator (tPA).
The trial is 60 Multistem and 60 placebo, but they are adding 6 additional Multistem and 2 placebo from cohort 2.
This brings the total to:
It is unbalanced, but this is ok. Also, I believe that Gil commented on cohort 2 outcome in a video. He suggested that Multistem performed well. They should include these patients, but it seems they are also motivated to include these patients. This is good.
If Multistem works, go to sealedenvelope sample size calculator and type in:
placebo success 15%
experimental success 36%
Sample size required per group 64
Total sample size required 128
128 patients are required to have a 80% chance of detecting (80% is good enough for me), as significant at the 5% level, an increase in the primary outcome measure from 15% in the control group to 36% in the experimental group.
So if our placebo and treatment groups stay at 15% and 36% for the 10% to 13% increase improvement with no more or no less improvement in the placebo and treatment respectively, we can call this study good. IMHO on the back of an envelope type deal. We would all like this, and lets hope so for the stroke victims which, hopefully not, but may be any of us some day.
QE_19, review the Edison report and clinical trial outline.
I do not believe that having received tissue plasminogen activator (tPA) or mechanical clot removal before the 24-48 hour windows is an exclusion criteria for the Multistem stroke trial.
For the Multistem stroke trial, Athersys simply selects patients who are remain moderate to severe on the stroke ratings after 24-48 hours, regardless of prior standard of care treatment (tPA, mechanical clot removal, aspirin, etc.)
This trial is not about missing a window, it is about any patients that does not improve by 24-48 hours following a stroke, regardless of prior standard of care treatment.
In other words, if you have a stroke in the hospital and are treated but do not improve by 24-48 hours under standard of care, you are Multistem eligible.
From Edison: "Waiting until 24-48 hours after a stroke, and then only selecting moderate-to-severe patients (8-20 NIHSS), eliminates the majority of ‘natural responders’ and should provide a greater chance of demonstrating a treatment effect."
Therefore, Multistem trial patients may have received any or all standard of care immediately after a stroke but qualify by not improving by 24-48 hours.
Guilty as charged, sir.
But, contributing to stroke recovery and proving it with a few patients is tough. Variation is high with strokes because there is always a range of neurological outcomes. This is exactly why stroke is a notorious indication.
The upside is big, but so is the downside. Gil has to be prepared for everything. If the primary is missed, he moves on to 30 day secondary outcomes and the radiology reports. He can always say that Multistem was found to be safe. Athersys has cash, so they have more shots on goal than most retailers can sustain.
Mixed stroke scale results would throw a tailspin into the reimbursement equation, but who would care if we got a signal of efficacy from at least one scale? I would take any scale being positive and rather be bought out with some good news rather than worry about reimbursement. Leave that to Pfizer or JNJ. I think this is what Gil is realizing and why he explained the different strokes scales offer different insights into recovery. Reimbursement is very hard to get these days without approvals.
Gil said that each scale told a slightly different story about stroke recovery which is needed to meet the primary outcome. Reimbursement concerns at this point are like asking for your money back during a crash landing. I will take any signal of success from any index or even a secondary outcome measure and worry about insurance claims later. We have to survive this phase 2 landing first. Buckle up!
The stated reason that Gil provided is that each stroke index measures a slightly different hue of stroke patient recovery to which I say, what took them so long to figure this out? Right survtech? What took them so long?
Why wait until the last minute to address this apparent essential element of data interpretation. If I go with the "stated reasons" as you suggest, we are in much worse shape than anyone is predicting because this would mean that Athersys obviously does not have a clue about what they are doing. They waited until the last minute to assign a global analysis which could mean the difference between success and failure, as defined by the primary outcome measure.
Lets hope that one of my explanations above is the REAL reason they change to global analysis, otherwise we are s-blued and tattooed.
I disagree with the proposal of any clinical trial for stroke with any arm not providing standard of care. No stroke doctor is going to forego clot removal using either tissue plasminogen activator (tPA) and/or mechanical approaches. Athersys's Multistem must be tested on top of all standard of care approaches for clot removal, so standard of care is the foundation for the Multistem stroke trial that we have to build upon.
On top of standard of care, including clot removal, Multistem has to demonstrate a contribution to the improvement of patient recovery, which Erlanger has explained is needed. Erlanger said therapy in addition to clot removal is needed, and this is why they are evaluating Multistem.
Having said this, there is considerable variability in stroke recovery, even in those patients in need who are stable non-responders to standard of care (clot removal) at 24-48 hours. The outcome of these patients at 90 days is a wild card, so determining Multistem's contribution may take hundreds of patients to definitively determine.
Athersys is well aware that their stroke trial is under powered, as most phase 2's for stroke are. Let's face it, neurological improvement can be all over the place, creating quite a numbers mess. This is why they have explicitly stated: "If MultiStem is safe and there is a SIGNAL of efficacy, a late stage phase IIb-III trial is planned." Int J Stroke. 2014 Apr;9(3):381-6. Notice they leave in the possibility of a phase IIb.
Furthermore, Phase 2's are early controlled clinical studies conducted to obtain some PRELIMINARY data on the effectiveness of the drug. So, forget everything riding of the primary outcome measure for stroke trials, we have to take a look at the 30 day secondary outcomes and all the radiology as well. Then, wait on a partner to decide the fate. Barring reaching the primary outcome measure in spades, we know this is going to be a tedious process. After stewing on Multistem for a long time, this is all IMHO.
We all know that Athersys changed its protocol to a more broad global test analysis that includes the Rankin Scale (mRS), NIHSS, and Barthel Index (BI).
This change was thought to be made to be more comprehensive for the 90 day stroke recovery assessment.
Now, Gil has told us exactly when the announcement will be made. The European Stroke Organisation Conference, 17-19 April 2015 in Glasgow, UK. He even said a few time they think Multistem will work.
So, the reason for the change to the global test analysis instead of going only with the Rankin Scale could be because the blinded data is showing abnormally high level of stroke recovery relative to established known natural progression of similar patients.
Therefore, all three scales might have been added, not to increase the likelihood of identifying success, but to showcase Multistem's ability to run the table on all three scales.
Keep in mind, however, Gil does have some 30 day data and scan data, so he may feel confident that even if the primary outcome measure is reached, he will have something positive to say about some of the data at the meeting to save face. In this case, all three test could be used to insure the data is mined upfront. Then, follow with the 30 day secondary data and radiology to leave the stage without too many rotten tomatoes.
This is just a hypothesis.
NCT01436487 on 2014_11_12