Thread by @MadhavThambiset

1/n Thoughts on Neurofilament Light (NfL) as a neurodegeneration biomarker. I expect to hear a lot on it in the upcoming #Tofersen Adcom. @US_FDA refers to it as a promising biomarker of neurodegeneration in several diseases at the Relyvrio #ALS approval👇@ProfRobHoward @pash22

2/n This raises an important question- if decreasing NfL levels are associated with clinical benefit outcomes in #ALS, wouldn’t increasing levels associated with worsening clinical outcomes and/or adverse events in #Alzheimer’s be similarly meaningful? Unfortunately these results

3/n have not been published for #aducanumab or #lecanemab. But they have for #donanemab by @LillyPad in phase-2 where accelerated loss of brain volume seen relative to placebo is associated with Increase in NfL levels. Increase in NFL is also significantly associated with faster

4/n progression. It would be important for the corresponding results from the completed phase-3 trials of #aducanumab and #lecanemab to be published. Are the losses in brain volume or increases in ventricular volume seen with both drugs associated with increases in NfL levels?

5/n If they are, the @US_FDA’s own rationale on NfL as a biomarker in the #Relyvrio approval in #ALS would suggest that these volumetric changes on brain MRI scans in amyloid antibody trials are worsening neurodegeneration in #Alzheimer’s. This is an important question relevant

6/n to patient safety. We now have two approved #Alzheimer drugs which have collected these data in completed phase-3 trials. These results should be published without further delay as @LillyPad has done. tinyurl.com/hmyvu6h4 Similarly important questions are whether

7/n frequency/severity of ARIA are associated with either higher baseline NfL levels or with increase in NfL over time. These are easily answerable questions of relevance in safety assessment of these drugs. These data have been collected & must be published without more delay.