Info Filtering Down re: AZD103.
Information is starting to filter down to us lowly shareholders...............
canadapiet.........."We have however to wait for more info about the real cause of the deaths."
All the deaths were categorized by the Independent Monitoring Safety Committee (ISMC) as being unrelated
to the Study Drug. Except for 1 Investigator out of the whole committee in 1 of the deaths classified it as related to the drug and this has been called questionable by the others.
The Expected Death Rate for a Mild/Moderate AD Patient Pop. is 2% - 4%. When you start to get over 5% the FDA threshold is crossed and a closer look is warranted. This AZD103 Phasell sits at 2.8%
so the total deaths are not what was used as total consideration for withdrawing the remaining High Dose Groups.
The fact that the deaths were skewed towards the High Dose Groups. 9 of the 10 were in the High Dose Groups.
The other death is unknown whether it is in Placebo or 250mg BID Dosing Cohort because Placebo and 250mg Arms are still blinded.
When coupled with a greater incidence of SAE's in the High Dose Groups compared to the 250mg BID the decision was made. IMO it wouldn't have been a difficult decision being so late in the game with lots of High Dose being finished already. When the Cohorts were Stratified with both High Dose Cohorts together as compared to Placebo/250mg BID together...................the High Dose Cohorts reached that 5% level. To not stop the High Doses with a 5% rate would leave Elan/Transition in a precarious legal position should even 1 death be found to be drug related later................ Err on the side of caution and Safety ........for sure!
The other interesting thing I found out today is that in this Phasell AZD103 has shown at the 6 Month mark that it achieved concentrations at a greater rate than shown in Phasel testing. Three times higher than Phasel's at ten days. The CSF levels of AZD103 at the 250mg dose at 6 months equaled the CSF levels achieved at the 2,000mg dose at 10 days, and the CSF levels of the 1000mg and 2000mg BID doses achieved at 6 months were above
what would be considered normal.
They have 12 month Data for this as well but it has yet to be fully analyzed..................... but pre-clinicals showed that Oral Gavage of AZD103 will plateau and not continue to accumulate. They expect that the 12 Month Data will not show significantly higher levels in the CSF than observed at 6 Months.
Therefore, Elan/Transition believe that the 250mg BID lower dose range (IMO 250mg - 400mg) will turn out to be the efficacious dosing with the good Safety Profile.
GLA..........