1/n Ahead of the much anticipated FDA Adcom on #lecanemab we outline key questions that physicians, payors & regulators must ask in the assessment of anti-amyloid antibodies. tinyurl.com/yrtnb2et @ProfRobHoward @kathy_y_liu @nvillain_alz @VincentPlanche @ayton_scott @SFAckley 2/n Many of these questions can be answered with existing RCT data but have not been reported by trial sponsors in peer-reviewed journals. Others may require RCTs with specific design features to test whether these are disease modifying treatments. Both incomplete & selective

1/n One of my favorite chapters is 6 ‘An Unlikely Trio’. Dr. Subbarow was one of the original ascetic-scientists, pursuing science as an end in itself rather than as a means to fame, wealth or adulation. I learned about him from my own scientist parents & through 👇

https://twitter.com/madhavthambiset/status/1639999124828291074

2/n this comic book. The cover illustration shows him being stopped by a cop who has spotted blood from the trunk of his car. He had to procure raw liver from the butcher’s to take back to his lab and extract folic acid which eventually led to the cure for pernicious anemia!

1/n Good point, Mike. I can use #solanezumab as a case study in selective reporting of RCT trial results which does not serve patient’s interests. Sola was discontinued despite pooled results from 2 ph-3 trials suggesting that ‘mild’ (but not ‘moderate’) stage #Alzheimer patients

https://twitter.com/michaelokun/status/1637453397363154947

2/n may benefit. But a 3rd ph-3 trial in only ‘mild’ AD was clearly negative. Presumed reason was that the Rx did not lower brain amyloid levels enough. Lilly published the MRI findings from these studies looking at brain volume changes. They considered these results important to

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

@adamfeuerstein @pash22 @a_charidimou @barttels2 @LonSchneiderMD @dmrind @gregggonsalves @AE_MD @ProfRobHoward @MemoryDoc @nvillain_alz @seb_walsh @AlbertoEspay @PhilAlz @ayton_scott @reshmagar @jasonkarlawish @KarlHerrup @GiovanniFrisoni @macesari @geoperry @samgandy @Gill_Livingston @Kariem_Ezzat @andrea_sturchio @AndaloussiLab @rkhamsi @r_merrick @DrLiHueiTsai @Jasonmmast @damiangarde @lauriemcginley2 @grace_huckins @aylinsdincer @PamBelluck @schrag_matthew @kathy_y_liu @biogen @EisaiUS @naomikresge @DrMariaALZ @alzassociation @barttels @StefanoSensi14 @KasperBJohnsen @US_FDA @KasperKepp @oncology_bg @VPrasadMDMPH Hi Adam- With all due respect, I am not sure what you are outraged about. I have been consistent as far as my worry about the side effects of these drugs are concerned including on STAT
tinyurl.com/5n86rdj2 @adamfeuerstein @pash22 @a_charidimou @barttels2 @LonSchneiderMD @dmrind @gregggonsalves @AE_MD @ProfRobHoward @MemoryDoc @nvillain_alz @seb_walsh @AlbertoEspay @PhilAlz @ayton_scott @reshmagar @jasonkarlawish @KarlHerrup @GiovanniFrisoni @macesari @geoperry @samgandy @Gill_Livingston @Kariem_Ezzat @andrea_sturchio @AndaloussiLab @rkhamsi @r_merrick @DrLiHueiTsai @Jasonmmast @damiangarde @lauriemcginley2 @grace_huckins @aylinsdincer @PamBelluck @schrag_matthew @kathy_y_liu @biogen @EisaiUS @naomikresge @DrMariaALZ @alzassociation @barttels @StefanoSensi14 @KasperBJohnsen @US_FDA @KasperKepp @oncology_bg @VPrasadMDMPH Previously on STAT, I called the aducanumab approval a “miscarriage of science”
statnews.com/2021/06/17/why…
I have described the CLARITY-AD trial a scientific milestone on live television.
tinyurl.com/2p92n4f9

1/n 🧵@LillyPad deserves credit for reporting TRAILBLAZER #donanemab results quickly Their blood biomarker results tinyurl.com/bdewaf7b show for the 1st time relationship between change in plasma NfL & brain volume @ProfRobHoward @pash22 @JohnCendpts @AlbertoEspay @Dereklowe 2/n I have long believed that NfL, a marker of neurodegeneration, will track with accelerated brain atrophy in amyloid lowering Rx including #donanemab👇 This indeed appears to be the case. NfL shows significant correlation with change in whole brain volume (R = –0.1710; P =0.03)

1/ BLAMING THE PATHWAY?
tinyurl.com/dp5t5njh
@AlzResearchUK tries to explain why EMA didn't approve #aducanumab as @US_FDA did. It seems to suggest that the lack of an accelerated approval pathway at EMA is the problem @ProfRobHoward @pash22 2/ "The FDA approved aducanumab via its Accelerated Approval Pathway. This means a licence can be granted based on a drug’s effect on a biological marker of disease, rather than its proven ability to improve people’s day-to-day lives. This meant the FDA was able to consider

@LonSchneiderMD #Adcom
DR. THAMBISETTY: I want to clarify whether
or not this question includes effects of the
biomarkers related to brain pathology as well as
reading out clinical effectiveness because those
are two completely different questions. I want to
be sure I understand

https://twitter.com/LonSchneiderMD/status/1402809505230909443

that the question is capturing one or the other, or both in this.
DR. FOUNTAIN: I think 1 understand the
question, and I think we can ask the FDA if we're
undecided, but I think we get to decide that. And
I think the question crosses anything you think
might be pharmacodynamic