Worst case scenario is it takes about 2 wks to clean data and lock data base. Then whatever it takes for the statisticians, no more than 1 wk to run a program, reassess, etc. We'll see...I'm hopeful.
Looks like trial was open on 5/31/2013. That would mean all logistics would be complete for at least some of their sites. Given the rate of enrollment, first dosing would have occurred in 6/2013 (usually there is a screening window between 21-28 days). With all that said, I could not find the date of first dosing.
I've always had to use colleagues that are statisticians or the stats department. I've said this before and I think it should be said again. Every day that passes makes our p value lower. Of course, the stats modeling guys can give you better details. The caveat is that there are a lot of variables (performance of comparator, time needed for data cleaning, database lock, and stats) so there may be a decent confidence interval on any assumptions. At this point, though, I do like our chance for being statistically significant and I'm surprised to see us red.
Injury to the break causing swelling and disruption of the endothelium (blood vessels) so that if blood flow is re-established inappropriately (clot-breaker), reperfusion causes bleeding.
You're right on. Patients who wake up with stroke symptoms (which is a significant percent, but I can't dig that up now) are NOT candidates for TPA because we cannot ascertain time of onset. Last time normal is when they went to sleep.
BTW, litigation post-TPA should only become a reality if it's administered against guidelines. In the informed consent process, hemorrhage is emphasized with family. A 6% hemorrhage rate was seen in the big academic TPA trials. Higher rates were seen in trials in the community. This did lead to some controversy over where TPA should be administered. I have to stop here...sorry.
This is well-documented to be the main risk of administering IV TPA. Trials have shown that the risk-benefit favors benefit up to 4.5 hours. After 4.5 hours, there is more risk of harm (i.e. hemorrhage). Unfortunately, the hemorrhage associated with TPA can be difficult to control as there is no factor that can easily control the bleeding (doc's try FFP and factor 7). The bottom line is that physicians try their best to ascertain the time of onset of symptoms (or as we put it, "last time seen normal"--this is used for people that fall asleep normal and wake up with a stroke). Stroke onset time, size of stroke, NIHSS, blood work--all of them factor into determining TPA eligibility. The eligibility feeds into risk-benefit. One additional point, mechanical clot retrieval does not use TPA and the therapeutic window is often extended based on lesion location and the appearance of the stroke on MRI. Intra-arterial TPA (at the site of the clot) does admin a small amount of TPA, but again the window is often extended.
I still don't feel Multistem is a competitor per se, but rather a complementary drug. The flexibility in a 36 window would be HUGE, and the safety profile is obviously in its favor.
I really think they need one to clarify all the confusion. I will urge IR to do so.
Perhaps the weekend conference made it impossible or the need for an early PR due to a leak, but im a little disturbed one hasn't been planned for Monday already
If you actually want to ask a question, ask a specific question. Ask something about the finances, management or the science. Most longs are here for the science and near term catalysts.
Sorry...Id like to see the stats for the primary endpoint for the 36 hr window, not just those with an excellent outcome. Its like they revealed a subgroup of a subgroup.
What we need to see is the average composite score compared to placebo, not just those with an excellent outcome. This will likely diminish the p value even in the 36 hr window. I have to believe the data was presented this way for a reason
I believe Chugai will agree. What I'm not knowledgeable about is Japan's regulatory process. I'm not sure if the current data will suffice for approval and marketing. As decent as the data looks, I don't believe it was a predefined endpoint. In my opinion, that's the million dollar question. If Japan's regulatory authority is happy with this, then this rebounds hard.
As far as the US, this is a huge unmet medical need. Absolutely huge market. The FDA will see safe treatment and signs of efficacy in a defined time window. There's no doubt they will allow ATHX to proceed. The question in my mind is how will it get funded--secondary, partnership, or simply a buyout.
I'm a buyer today.
I'll keep this simple. After stroke, there is disruption of the BBB (blood brain barrier), leading to swelling and infiltration of inflammatory cells. Multistem is supposed to reduce this infiltration of cells and reduce secondary injury. In my experience, swelling becomes evident around 24 hours, peaks between 72-96 hours. The swelling is likely to correlate to the presence of inflammatory cells--I'm sure I could find many studies to support that.
Timing is everything. This is evident with TPA and seems to be evident here. If you wait to long to cut out the influx of inflammatory cells, then the secondary injury cascade has already propagated too far. The problem for ATHX is they didn't know where the therapeutic window is. It appears that up to 36 hours has a good chance at + efficacy in P3.