[Conductor71]

Not sure that anyone has posted this info on PDOR. The summit generated what looks to be like an intense discussion and I'd say that the key words or ideas center on biomarkers and the FDA hurdles involved in proving "disease modification" (inadequate measure in placebo controls).

Interestingly, Franz Hefti of Avid Pharmaceuticals comments on the 'druggability' of alpha-synuclein as a viable treatment concluded with some interesting statements on how a clinical trial might look like; I like that there is a clear drive or mandate to move beyond dopa and placebo measures.

Alpha Synuclein MJFF Summary and Outcomes

Some key things that were said about what a potential Alpha clinical trial might look like:


• High hurdle for doing trials in non-symptomatic “patients”.
• FDA approves drugs “for the treatment of Parkinson’s disease” based on
difference to placebo in controlled trials.
• “Disease modification” is not necessary for approval, thus the hurdle for
such a specific claim in the label is high.
• Differences in rates of progression are not sufficient
• A claim for ‘disease modification’ must be forced on the FDA
• based on disease mechanism data (incl. surrogate markers)
• example: current discussions on anti-A therapy in AD

Clinical trials using behavior and dopaminergic neuron
degeneration as outcome measures long and costly
• Seek alternative outcome measures which reflect
-synuclein-related pathology more directly than
dopaminergic neuron degeneration

Glad to see that their concerns echo what we have been voicing. One thing I'm wondering...is alpha-synuclein treatment being targeted for early (pre-motor) symptom PD only, or might we all benefit from it? There seems to be a big focus on how they could treat asymptomatic (pre-motor symptoms) and the need for biomarkers?

Laura