Lecanemab is a drug that targets amyloid, a protein associated with the development of Alzheimer’s disease and develops years (if not decades) before symptoms of the disease develop. This new drug reduces amyloid in the brain, and studies show that this directly reduces the chance of going on to develop the disease. Its approval is incredibly important for our ability to treat and prevent Alzheimer’s disease.
Please note that this drug cannot reverse or cure Alzheimer’s disease. It is a preventative only. Once dementia develops, that means brain damage has already occurred, and you can’t reverse brain damage.
You can test for amyloid, yes. The most common method is a PET scan using a tracer (ingestible marker) that sticks to amyloid and “lights up” in the scan. However there are new blood tests that works fairly well, and are getting better (but from personal experience are not as accurate as a PET scan).
You would get a prescription if you meet the criteria. First, you would need to have abnormally high amyloid levels but without any other signs or symptoms of Alzheimer’s (like cognitive impairment). This is because this drug targets only the first stage (amyloid), but not any progressive stage. You would also need to meet some other criteria to determine that you are both eligible and a good candidate for it to work (e.g. no history of strokes or other brain injury). The drug is also at the moment not covered by any insurance, so you would be paying quite a bit, however this will likely change in the near future.
Great insight into the clinical process of Alzheimers care. I have worked on Amyloid programs before (early stage pharma R&D), and was wondering if there are significant clinical differences between lecanemab and aducanumab that makes you think this approval will have a less problematic trajectory? From my perspective, they are both mAbs targeting the same thing, but the discussion around lecanemab is different than it was for aducanumab, but perhaps that was primarily due to the non-standard phase 3 process of adu.
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.
Lecanemab is a drug that targets amyloid, a protein associated with the development of Alzheimer’s disease and develops years (if not decades) before symptoms of the disease develop. This new drug reduces amyloid in the brain, and studies show that this directly reduces the chance of going on to develop the disease. Its approval is incredibly important for our ability to treat and prevent Alzheimer’s disease.
Please note that this drug cannot reverse or cure Alzheimer’s disease. It is a preventative only. Once dementia develops, that means brain damage has already occurred, and you can’t reverse brain damage.
That’s incredible! So how would this be prescribed? Can you test for the presence of amyloid? Are there precursors?
You can test for amyloid, yes. The most common method is a PET scan using a tracer (ingestible marker) that sticks to amyloid and “lights up” in the scan. However there are new blood tests that works fairly well, and are getting better (but from personal experience are not as accurate as a PET scan).
You would get a prescription if you meet the criteria. First, you would need to have abnormally high amyloid levels but without any other signs or symptoms of Alzheimer’s (like cognitive impairment). This is because this drug targets only the first stage (amyloid), but not any progressive stage. You would also need to meet some other criteria to determine that you are both eligible and a good candidate for it to work (e.g. no history of strokes or other brain injury). The drug is also at the moment not covered by any insurance, so you would be paying quite a bit, however this will likely change in the near future.
Great insight into the clinical process of Alzheimers care. I have worked on Amyloid programs before (early stage pharma R&D), and was wondering if there are significant clinical differences between lecanemab and aducanumab that makes you think this approval will have a less problematic trajectory? From my perspective, they are both mAbs targeting the same thing, but the discussion around lecanemab is different than it was for aducanumab, but perhaps that was primarily due to the non-standard phase 3 process of adu.
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.