Recent results from Prana Biotechnology’s IMAGINE Alzheimer’s trial, released earlier this year (March), as well as the company’s ongoing sub-analysis, has suggested to the company’s research team that further analysis of the PiB-PET Standardized Uptake Value Ratio (SUVR) and the tendency towards preservation of brain volume in PBT2 treated patients may be necessary.
The results of the ongoing analysis will allow Prana to readjust future trials, explained Dr. Colin Masters, Executive Director at Mental Health Research Institute and professor at the University of Melbourne, who also collaborates with the pharmaceutical industry and biotechnology companies in discovering compounds that can inhibit the production or aggregation of amyloid in an Alzheimer’s patient’s brain.
After the first results of the study suggested the potential benefits of PBT2 in reducing amyloid burden levels, further sub-analyses were performed, including one measuring the effects of a daily dose of 250 mg of PBT2 throughout a year of treatment.
This trial managed to enroll 42 patients, 27 who took PBT2 and 15 who took a placebo.
The goal of the trial was to determine if amyloid burden would decrease in patients using PBT2 when compared to the group using placebo. The company recently noted on its webpage that “Prana’s PBT2 did not meet its primary endpoint,” since a reduction in both groups and not just in the PBT2 group affected the study results.
Prana offered further analysis for understanding the unexpected behavior of the placebo group.
As Masters explained, “the starting amyloid burden level in the PBT2 group had an important bearing on the decrease of amyloid over time in that participant, whereas there was no such correlation in the placebo group.”
To better understand these responses, Masters performed another test and found that patients using a SUVR above 2.5 met a significant reduction in amyloid burden levels not observed in patients using placebo or SUVR below 2.5.
According to a recent press release, Masters suggested that even though this was a small trial that featured an atypical placebo group response, there are still “previous clinical findings, the strong body of peer-reviewed science, along with the sub-analysis of IMAGINE” that support the company’s enthusiasm “about the prospects of a large trial statistically powered to demonstrate cognitive benefit,” he said.
The trend of reduced brain atrophy observed when using PBT2 reflects the company’s preclinical observations and corroborates a similar tendency observed in the Reach2HD Huntington’s trial.
PBT2 appears to activate intracellular signing pathways that promote neuronal plasticity and to prevent the formation and toxicity of Abeta species by boosting their removal.