Thread by @PTenigma

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

Atrophy was GREATER in the treatment arm in terms of cortical thickness (did I hear that right??) but hippocampal atrophy was slowed; #CTAD2022 there will be an open label extension of this trial now ….

Quality of life also reported to be better (less decline) including in the carer burden assessments offering meaningful benefits to patients and society of an amyloid protofibril targeted therapy #CTAD2022

ARIA is a very important adverse event - and is higher with treatment and is symptomatic in 2.8 percent overall - and monitoring and management and appropriate use recommendations are crucial

Overall in people on anticoagulants the incidence of ARIA is higher. MRI monitoring will be valuable early in treatment, and will need to be graded to decide if treatment should be interrupted

Tp be eligible, we need someone to be amyloid positive to qualify and in the mild stage of the disease, MCI or mild dementia, and able to undergo MRI to assess safety.

This trial did not exclude people with many comorbidities and included ancestral diversity and broad age range

Lecanemab also impacts tau and phosphotau. “There is hope to buy time in this progressive disease.”

In subgroup analyses we have to be cautious. The decline in the placebo arm of the ApoE4 homozygotes was not severe in the CDR-SB but lecanemab showed benefit for ApoE4 homozygotes on the other clinical trial endpoints, including plasma and caregiver burden