Prana just reported that PBT2 did not produce benefit vis-a-vis AB plaque load, cognition, or metabolic function in their latest Phase II trial in prodromal/mild Alzheimer’s. A nonsignificant trend towards slowed hippocampal atrophy (2.6% vs. 4.2%) over twelve months was reported, consistent with what was reported from their Huntington’s PhII.
What does this establish about PBT2 in AD specifically, and in neurodegeneration in general? About as much as might be expected from a 42pt trial–virtually nothing. Anyone who expected to see cognitive benefit from this size trial has not been paying attention, and had there been an impact on plaque volume, we would have been raising the question of whether this was good, bad, or irrelevant. Even the meaning of the hippocampal volume trend is impossible to establish–it was the measure that NIR was more interested in, since we wanted to see if there was anything to substantiate the ‘signal’ suggested by the six patient(!) cohort in the HD trial–but even so, we have no idea whether it reflects a genuine effect upon the degenerative process or not.
One must question Prana’s judgment in running this study. AD trials these days look at eighteen-month duration effects in thousands of patients; this may be the most underpowered Alzheimer’s trial in recorded history. As we said in the January issue of NeuroPerspective: “It will be hard to find anything conclusive with just 40 patients, but they will be looking hard for trends.”
The net effect will be to undercut Prana’s already borderline credibility, and hinder–perhaps fatally–their ability to follow up on the hotly debated, ambiguous-at-best Huntington’s data. It would have been a near-miracle for it to be otherwise. Why did they bother?