Hippocampal Atrophy Reduction - Importance

This is really important. We saw a reduction of 35% in hippocampal atrophy ("HA" or brain shrinking) in the treated group over the first year of IMAGINE. HA is directly linked to loss of cognition and if the placebos that started receiving PBT2 in the extension trial (qualifying as a random delayed start) cross over to protection of HA atrophy and "fail to catch up (after a reasonable period of time) to patients who received active treatment for the entire duration of the trial, a disease modifying effect of treatment would have been shown." This would qualify IMAGINE as the first known trial to show evidence of a disease modifying therapy as specified below as Kad posted yesterday on ymb..

ITM, if the crossovers from placebo improve their rate of hippocampus atrophy, after receiving the drug, it would be clear evidence of disease modification.
From the FDA Alzheimer's trial guidance document.
" A randomized-start or randomized-withdrawal trial design (with clinical outcome measures) appears to be a more convincing means of demonstrating such an effect. For ethical reasons, a randomized-start design would be most appropriate for use in AD. In this study design, patients are randomized to drug and placebo, and at some point, placebo patients are crossed over to active treatment. If patients in the trial who were initially on placebo then assigned to active treatment fail to catch up (after a reasonable period of time) to patients who received active treatment for the entire duration of the trial, a disease modifying effect of treatment would have been shown. We are unaware of any instances to date where this design has been successfully used in a clinical trial to establish a disease modifying effect."

Lots of research has been done to show that preservation of hippocampal volume is related to preservation of cognition.