Discover and read the best of Twitter Threads about #lecanemab
Most recents (15)
I want to show you what microhemorrhages and brain swelling from anti-amyloid immunotherapies look like under a microscope. In this severe case, many of the vessels simply disintegrated - see the bleeding and numerous aneurysms in this striking image. #Alzheimer #lecanemab
This is a piece of human brain from a patient who died from a side effect of the Alzheimer's drug lecanemab. The tissue is about 2.5 x 2.5 x 1cm and has been "cleared", allowing us to see the vessels in three dimensions using a type of microscope called a lightsheet.
The video shows a 3D rendering of the tissue block with vessels false-colored pink. The hazy background around some of the vessels (see yellow arrows) is from bleeding (the ruptured ends of the vessel are at the red arrows). Blood propagates in perivascular spaces some distance. 
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
3/n reporting of RCT results as well as statistically inappropriate interpretation of existing data undermine the validity of these carefully run & challenging experiments in human patients in trial centers across the world. We specify three key questions in assessing these Rx
📢Hoy se adelantan los resultados del estudio con nuevo tratamiento anti-amiloide (#Donanemab) con ensayo clínico Fas 3 aparentemente exitoso para fases precoces del #Alzheimer 🧠.
👇
investor.lilly.com/news-releases/…
Resultados interesantes, pero todavía con cautela!
#neurologia #Salud
👇
investor.lilly.com/news-releases/…
Resultados interesantes, pero todavía con cautela!
#neurologia #Salud
En julio en el congreso de la Alzheimer's Association en Amsterdam tendremos más información.
Lo interesante de los resultados es que:
👉 #Donanemab va en la misma línea que #Lecanemab y #Aducanumab (otros anti-amiloide).
👉 Importancia del diagnóstico precoz (pre-demencia).
Lo interesante de los resultados es que:
👉 #Donanemab va en la misma línea que #Lecanemab y #Aducanumab (otros anti-amiloide).
👉 Importancia del diagnóstico precoz (pre-demencia).
Estos estudios van a favor de:
👉 La necesidad de #diagnóstico temprano del #Alzheimer pre-demencia y confirmación diagnóstica mediante #biomarcadores .
👉 Necesidad de apostar por una política de #SaludPública diferente en el campo del #deteriorocognitivo
#Sociedad
👉 La necesidad de #diagnóstico temprano del #Alzheimer pre-demencia y confirmación diagnóstica mediante #biomarcadores .
👉 Necesidad de apostar por una política de #SaludPública diferente en el campo del #deteriorocognitivo
#Sociedad
@MadhavThambiset was the voice of reason at the #AANAM. He delivered a Neurology Year in Review Plenary about the dubious record of the anti-proteinopathy framework inspiring therapies in #Alzheimers, #Parkinsons, and #ALS --Some highlights (1/4)
(2/4) Unblinding due to infusion-related reactions or ARIA-H was not accounted for in the sensitivity analysis of the #lecanemab trial. This and other issues have led to an inflated sense of efficacy and underestimated risk for anti-amyloid therapies.
(3/4) What's the magnitude of brain loss induced by lecanemab over the course of the trial? 3 fewer "teaspoons" of brain lost at the highest ('therapeutic') dose of lecanemab.
1- A thread on the value of treating #Alzheimer’s disease w/ monoclonal antibodies:
As I read through the recently published appropriate use guidelines for #lecanemab, I am struck by the infrastructure & resources that will be necessary.
#GeriTwitter
link.springer.com/article/10.142….
As I read through the recently published appropriate use guidelines for #lecanemab, I am struck by the infrastructure & resources that will be necessary.
#GeriTwitter
link.springer.com/article/10.142….
2- This table summarizes what medical centers need to safely administer lecanemab to people with Alzheimer’s disease.
Lecanemab is given via IV infusion every two weeks. This requires having an infusion center with the needed capacity & appropriately trained staff.
Lecanemab is given via IV infusion every two weeks. This requires having an infusion center with the needed capacity & appropriately trained staff.
3- Before treatment begins, you need to make a diagnosis.
You need clinicians skilled at diagnosing mild cognitive impairment & mild dementia.
These are usually neurologists but could be geriatricians or geriatric psychiatrists. There aren’t a ton of folks with this skillset.
You need clinicians skilled at diagnosing mild cognitive impairment & mild dementia.
These are usually neurologists but could be geriatricians or geriatric psychiatrists. There aren’t a ton of folks with this skillset.
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
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
3/n report because they noted that “Rates of whole brain volume & ventricular volume changes are sensitive markers of neurodegeneration & used as biomarker outcome measures in trials of potential disease‐modifying therapies.” tinyurl.com/33a7dkh3 They also reported on the
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
Trial data shows new FDA-approved Alzheimer's drug #lecanemab can lead to 'brain shrinkage'.
Advocacy groups celebrate its approval but critics question if the benefits outweigh harms & object to FDA decision without input from advisory committee.
maryannedemasi.substack.com/p/alzheimers-d… @RxRegA
Advocacy groups celebrate its approval but critics question if the benefits outweigh harms & object to FDA decision without input from advisory committee.
maryannedemasi.substack.com/p/alzheimers-d… @RxRegA
No FDA advisory panel?
"The FDA once again has shown a lack of concern for the public, patients, and healthcare providers. Convening its advisory panel would have helped reassure everyone that the FDA’s decision was scientifically sound and transparent,” said @woodymatters
"The FDA once again has shown a lack of concern for the public, patients, and healthcare providers. Convening its advisory panel would have helped reassure everyone that the FDA’s decision was scientifically sound and transparent,” said @woodymatters
FDA 'accelerated' approval of #lecanumab accepted lower burden of proof for benefit e.g. showing lower amyloid protein in brain (surrogate marker) instead of showing a clinically meaningful benefit for person with Alzheimer's disease on a day-to-day basis.
🛑🛑Tras la repercusión del tuit de abajo sobre un artículo resumen de los ensayos clínicos más prometedores de 2023 publicado en @Nature y un sondeo positivo sobre resumir o no su contenido, me dispongo a ello.
pd. Aportaré info adicional y actualizando en estos días
Vamos🧵
pd. Aportaré info adicional y actualizando en estos días
Vamos🧵
1º varias notas aclaratorias:
-En la pieza de @Nature le preguntan a 11 investigadores sobre ensayos, de su área de estudio, prometedores o esperados en 2023. Yo resumiré lo que dicen y aportaré información adicional
-En la pieza de @Nature le preguntan a 11 investigadores sobre ensayos, de su área de estudio, prometedores o esperados en 2023. Yo resumiré lo que dicen y aportaré información adicional
- Clinicaltrials.gov es una web donde se registran los ensayos clínicos, se informa de todo lo relacionado con su diseño, objetivos, resultados que se esperan, equipos implicados, fármacos que se van a usar y en qué enfermedad y otras cosas más
We have tested the antibody in various doses on 856 patients on 3 continents. After only 6 months we observed positive results, and after 18 months 81% of the group receiving the highest dosage showed lower levels of amyloid beta than the level we measure in Alzheimer’s-Lannfelt
“The idea for the antibody originated back in the 1990s, when the team identified a change in the genetic material of a Swedish family that had been severely afflicted by Alzheimer's disease. The mutation indicated that the cause seemed to be protofibrils”
medicalxpress.com/news/2018-10-a…
medicalxpress.com/news/2018-10-a…
Overnight a Swedish professor made $350 million. The lucky man, Lars Lannfelt, was not particularly famous. He had done pioneering work on Alzheimer’s, but it was in the 90s and belonged to a sub-field that, after a litany of failures had fallen from grace
statnews.com/2022/10/11/for…
statnews.com/2022/10/11/for…
Right now, we're going after the pathology of the disease–plaques & tangles-but I think we need to start going after the biology and, as a result, the pharmacology that addresses the altered biology with aging that occurs in Alzheimer's-@a_hfillit @TheADDF
biospace.com/article/ctad-2…
biospace.com/article/ctad-2…
“Lecanemab slows #cognitivedecline. But this is only a start to stopping Alzheimer’s in its tracks. We have a lot of ground to cover to get from the 27% slowing #lecanemab offers to our goal of slowing cognitive decline by 100%"-@a_hfillit on #CTAD22 data
alzdiscovery.org/news-room/anno…
alzdiscovery.org/news-room/anno…
“The mixed data shows that while anti-amyloids are a promising starting point, we will need a combination of drugs aimed at different targets informed by the biology of aging to effectively treat this disease”
-@a_hfillit, M.D., co-founder and CSO @TheADDF
fiercebiotech.com/biotech/roche-…
-@a_hfillit, M.D., co-founder and CSO @TheADDF
fiercebiotech.com/biotech/roche-…
Yeni duyurulan #Alzheimer ilacı #lecanemab umut verici bir gelişmeye işaret ediyor, ancak bu ilaç yolun sonu değil. Bunun yanında, ilacın klinik çalışma sonuçları, ilacın hastalığın seyrini değiştirebileceği yönünde güçlü bir veri sunmuyor. Kısaca açıklamaya çalışayım.
Alzheimer durumunda beyinde oluşan plak yapılarının içindeki protein amiloid beta 42. Bu ilaç, bir önceki Aducanumab gibi monoklonal antikor yani amiloid beta 42’ye bağlanan özel bir protein. Bağlandığı zaman plakları bozarak Alzheimer patolojisini azaltan bir uygulama.
Öncekiler gibi bu antikor da plakları azaltıyor. Öncekinden farklı olarak, bu seferki antikor hastalığın bilişsel anlamdaki semptomlarına ilk 15 ay için azaltıcı özellik göstermekte. Buraya kadar her şey çok güzel görünüyor. Ama dahası var.
Today’s exciting #lecanemab results offer our best hope yet for not only delaying symptom progression for people with early stage Alzheimer’s, but, significantly, slowing the loss of quality of life for them and their carers. @RichJamesOakley explains from #CTAD22.
He added we were pleased to see a recommitment to the National Dementia Mission on Monday but said this crucial doubling of dementia research funding must be delivered urgently to boost research for all types of dementia so no one is forgotten.
Thank you for all of the interest in these exciting drug developments. Please bear with us while we work through your questions; our research team are in San Francisco at the Clinical Trials in Alzheimer’s Disease conference. More info on lecanemab here: alzheimers.org.uk/blog/three-pro…
BREAKING NEWS: New #Alzheimer drug #Lecanemab slows cognitive decline (18-month change in CDR-SB) by 27%, drastically lowers brain amyloid load by 59 centiloids to 23 (below PET amyloid positivity)! NEJM paper: nejm.org/doi/full/10.10… prnewswire.com/news-releases/… #CTAD
Randy Bateman notes that lecanemab reverses amyloid levels; 20 centiloid drop in amyloid levels at 3 months and 50 centiloid drop by 1 year on neuroimaging measures #CTAD2022
..also slows decreases in the rate of tau accumulation in the temporal lobes which is important for cognition #CTAD2022
“Today’s announcement gives patients and their families hope that lecanemab, if approved, can potentially slow the progression of Alzheimer’s disease, and provide a clinically meaningful impact on cognition and function,” said Michel Vounatsos, Chief Executive Officer at Biogen."
"Importantly, the study shows that removal of aggregated amyloid beta in the brain is associated with a slowing of disease in patients at the early stage of the disease" said Michel Vounatsos, CEO Biogen.
