We have 2 questions: how long time does it take to stop the progressive brain atrophy (or slow it down ) and what is the right dosage, 250mg or more.
The extension study will demonstrate if 2y is better than 1y in getting rid of amyloid. The result looks kind of self clear but nothing is self clear. It has been slowly accumulating for years, may be it also takes a lot more than 1y to get rid of it. We will get soon also the figures of soluble amyloid after 1 y treatment, but only the change in plasma.
In the old wonderful mouse studies by Adlard in 2011 and 2014 succesful PBT2 treatment was given only 11 days but 30mg/kg. Mice live perhaps only 2 y but humans 40 times longer. So 12 days of mouse life could "correspond" to 480 days of human life ( I know this is not the most likely correct way to do comparison). So the "corresponding time " to evaluate the effect of PBT2 in humans would be some 1y and 4 months. So according to this "calculation" the extension study could perhaps demonstrate much stronger efficacy than the 1y Imagine study also in the atrophy rate.
Dosage is even more open issue if we compare the mice studies with Imagine. The mice got 30mg/kg, but in the Imagine study the dosage was only about 3.6mg /kg. Many have recommended bigger dosage for humans because there has not been so strong evidence as there was in the mice studies and because PBT2 is very safe with this 250mg/day. With this very low dosage you could think that even longer time of treatment could give better results in all parameters as hippocampus atrophy, amyloid clearance and cognition. Cognition change perhaps is most difficult to evaluate because there is no placebo group in the extension study. But anyhow it is very interesting to see the results of the extension study.
I agree. The results of the PBT1 Phase IIa extension study a decade or so ago were pretty interesting to me, but they didn't impress Big Pharma. The IMAGINE extension study is better-designed than was the PBT1 extension, however, with a lot more stuff being measured. Even if the extension doesn't impress Wall Street of Big Pharma, I suspect that we will learn some things from it that will be useful going forward.
I’m not sure that “better-designed” (and certainly not “well-designed”) should even be used in the same sentence as the Imagine trials.
Other than selecting the wrong primary endpoint; choosing biomarkers unproven by previous PBT2 studies; possibly mismatching the target population and the cognitive/functional tests; having a pathetically small placebo group; under-populating the entire trial; quite possibly (personal opinion) waffling up the test arms/dosing/chain of custody; choosing the wrong statistical design (comparing group averages instead of average patient changes); failing to include a higher dose arm; having their own chief scientist disparage the test design in the CC; and burning up another couple years -- yeah, they did fine.
I won’t even go into the mishandling of questions at the CC, which made it all sound worse than it was. Because that would only divert from the point. Namely, there didn’t have to be #$%$ results in the first place.
This is chemistry. Proven on numerous animal studies both transgenic and wild-type to have dramatic, unambiguous (not merely positive) results. And very promising findings on the 2008 AD trials, even more so when subsequently reanalyzed. Failure to build on that speaks to competence and judgment.
Bottom line: Imagine should never have been labeled as a clinical trial. It was a useful, interesting and revelatory pre-trial experiment on a small patient population. To declare it an AD clinical trial and thereby tie the company future to its results invites the outcome that just occurred, and invites the ipso facto conclusion that PBT2 doesn’t work. When nothing could be further from the truth.