The trajectory of aducaumab was unfortunate as it only marginally failed the clinical trials, but fortunate in that its successor lecanumab is less associated with negative side effects (particularly ARIA or “brain bleed”) but is just as (if not more) effective.
There was also some controversy in the rush for approval for aducanumab, which was done mainly to ensure that people at risk for Alzheimer’s could get treatment before they progressed and became ineligible. Of course, this also rubbed some people the wrong way as it probably should have gone through more trials before its approval. Lecanumab did not go through this same “rushed” approval process.
Thanks for the explanation! I was curious how the targeting differed between the two mAbs and found a paper that explains:
Specifically, lecanemab mainly targets Aβ protofibrils, while aducanumab and other monoclonal antibodies favour highly aggregated forms of Aβ [5]. This differing target profile may also explain a substantially lower incidence of amyloid related imaging abnormalities, such as transient immunotherapy-related brain oedema and microbleeds, with lecanemab.
In other words, lecanemab seems to bind and remove Aβ before it aggregates, while other therapies (aducanumab) bind and then remove it after aggregation occurs.
The trajectory of aducaumab was unfortunate as it only marginally failed the clinical trials, but fortunate in that its successor lecanumab is less associated with negative side effects (particularly ARIA or “brain bleed”) but is just as (if not more) effective.
There was also some controversy in the rush for approval for aducanumab, which was done mainly to ensure that people at risk for Alzheimer’s could get treatment before they progressed and became ineligible. Of course, this also rubbed some people the wrong way as it probably should have gone through more trials before its approval. Lecanumab did not go through this same “rushed” approval process.
Thanks for the explanation! I was curious how the targeting differed between the two mAbs and found a paper that explains:
In other words, lecanemab seems to bind and remove Aβ before it aggregates, while other therapies (aducanumab) bind and then remove it after aggregation occurs.