AZD103 Trial Ongoing....The Numbers..
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QUOTE...Menghis Bairu, M.D., EVP, Chief Medical Officer and Head of Global Development at Elan.
"We continue to expect the ongoing study to provide important data to guide the next steps in the development of ELND005 (AZD103) for the potential treatment of Alzheimer's disease."
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The market has overreacted here. Great time to buy some more this week during tax loss seasson."
The market has assumed that this Trial is over and it is far from over. This was a Safety and Tolerability Phasell Trial that was designed to be a Pivotal Trial with an enrollment of 353 Patients.That's twice as many as required to qualify as a Pivotal Trial. As a Safety and Tolerability Trial first it has acomplished what it was supposed to do. Test the Tolerability and the Safety.
That being said the 2 High Dose Cohorts were waaaaay above Efficacious Doses seen in Pre-Clinicals.
The 1000mg BID Cohort was 420% Higher than the Dosing seen to be effective and the 2000mg BID was about 835% Higher than the dosing seen to be effective........in Pre-Clinicals.
The Lower Dose of 250mg BID was just slightly higher than Pre-Clinicals. This is the Dosing that continues uninterrupted.
Those interested have to consider that there is going to be a lot of Data coming from the 2 High Dose Cohorts. There were a lot of them that were Completers. A good 2/3rds to 3/4s of them would have already completed dosing. Even if we assume that only 2/3rds had finished there would still be 117 Completers. Heres some numbers to consider........
I think the market assumes that the trial lost half or 177 patients of 353 enrolled. This isn't the actual number and is quite a bit less.I don't believe that the withdrawal of the remaining high dose participants will result in all that many patients dropping out.
This is Week 97 of a 78 week Trial. 2/3 to 3/4 of participants should be done
their 78 weeks. Back of the napkin calculations are 44-60 patients will have been dropped by Mgnt. out of 353. ( NOT 177 )
We'll use the lower Completers numbers at 2/3rds ( 60 patients withdrawn) and Even with the rule of thumb of 10% dropout rate ( 35 more) for all cohorts is execised here (including placebo)......... there would be
258 Patient Completers.
Total 95 drop-out/withdrawn Participants
So if we accept the back of napkin numbers (even though i think 10% blanket dropout rate is way higher than actual) then this trial can still show Statistical Significance
----79.5 Placebo completers
----79.5 250mg completers
----49.5 1000mg completers
----49.5 2000mg completers
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178.5 treatment / 79.5 placebo Total 258 Completers
Thats a ratio of 2.2 to 1..........instead of original 3.0 to 1 ........ but this trial was actually looked at after the fact and Transition had opined that they thought it may be over powered on the dosing as compared to Placebo ( ie: not enough Placebos for the amount of Treated). Seems in a round about way that it worked out to the benefit
of this concern regarding how it was Powered to see Efficacy as well as Safety and Tolerability.
These High Dose Completers Data is going to be very important. Pre-Clinicals showed that efficacy was Dose Dependant. Dosing of 250mg BID......325 mg BID (35% higher).........400mg BID (67% higher) will probably
be the dosing used in the next Trial if they have 3 dosing cohorts. Then again 300mg BID and 350mg BID may be
a better bet for a full Phaselll Trial. ( just 2 Dosing Cohorts and Placebo Group)..........Anyways, the High Dose Data will be used as well to help determine these Doses for the Phaselll Trial.
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Heres something to consider ........Remember Flurizan?? The percentage of patients that died (42 died) in Myriad's Flurizan 18 month Alzheimers Phaselll that had 1,684 patients was exactly what AZD103's percentage is now in this large Phasell Trial. Two and a half percent. 2 1/2% It is to be expected that deaths occur when dealing with very elderly patient groups. Alzheimers is a terrible disease and the fatality rate of Alzheimer's Disease remains at 100%......Individuals with Alzheimer's disease often die of a medical complication such as
Pneumonia
or the Flu.
https://alzheimers.about.com/od/whatisalzheimer1/qt/prognosis.htm
Flu season is upon us.............. H1N1 Flu makes it a double threat this year.