It is one of the best articles I have read on the new drug.
I have pulled out excerpts and edited it to make it easier for Alzheimer's patients like myself to understand.
“The monoclonal antibody treatment aimed to slow the progression of memory and cognitive problems arising early in AD by decreasing amyloid beta in the brain,
a potential disease-modifying treatment is unlike the four approved drugs for AD, which treat symptoms of the disease and not the disease itself.” (such as Namzaric that I have been taking for my Alzheimers for the last 39 months)
‘However, there is certainly controversy and considerable public debate around the drug’s approval; after the FDA approved the treatment, three FDA advisory panel members resigned, which you can read more about here. But controversial or not, the fact of the matter is that the drug is now in the arsenal of drug treatment for AD, and with that, I am interested in what the drug’s approval means for AD clinical care going forward.
As of now, there are as many questions as answers, involving the
1-real-world efficacy,
2-safety, and
3-application of the drug.”
“As part of aducanumab’s accelerated approval, the FDA requires Biogen (the pharmaceutical company that manufactures aducanumab under the brand name Aduhelm) to complete a phase 4 confirmatory trial to verify the drug’s clinical benefit.
Additional information on the drug’s safety and efficacy will also come from its use in clinical practice, which will shape its clinical use applications.
Doctors will see patterns and eventually may be able to stratify the patient population receiving the drug by who best responds, if it is well tolerated, and where side effects lie.
The questions around the safety and efficacy of the drug exacerbate the explicit cost of the drug, both financial and experiential. The drug costs 56,000 dollars a year.
There is also ambiguity around how to use the drug, which may sound like an unexpected unknown for a drug that has just been approved by the FDA.
The clinical trial was very specific about how the drug was used:
to treat patients in the mild cognitive impairment stage of AD who had amyloid beta—” I met this criteria myself and decided not to take it yet with the advice of Dr Russll Swerdlow at KUMC Memory Center.
” The drug was approved based on its ability to reduce amyloid in the brain (which is correlated with improving mild cognitive impairment),
rather than based on a clinical measure such as delaying cognitive decline.
In real-world treatment, however, the standard of care does not often include diagnostic methods to evaluate the presence or absence of amyloid beta in patients with AD; rather, treatment guidance relies more on cognitive and daily functional assessments.
In terms of amyloid beta assessments,
1- positron emission tomography brain scans used to image beta-amyloid are expensive, 2- spinal taps that can test for the marker are invasive, and
3-blood tests are only just emerging and are not (yet) widely used.
There is further uncertainty around prescribing aducanumab because the FDA explicitly left the directions for who should get the drug general: while the clinical trial was very specific about how the drug was used, the drug label does not include any criteria limiting its indication to a subset of patients.
Whether or not you have read the fine print, many of you have likely seen an insert that comes with a prescribed medication. Generally speaking, before a patient starts a drug treatment, every doctor has to read the accompanying package insert.
The insert is like a playbook for giving the drug;
it includes details and directions, such as
1-what the drug is indicated for,
2- possible side effects from taking it,
3- dosage, and
4- how to administer it.
The opening line of the package insert of aducanumab, under the brand name Aduhelm, says that it is indicated for the treatment of Alzheimer’s disease. Full stop.
As AD is a spectrum that ranges from:
1- Stage 1 Preclinical (asymptomatic) disease, to
2-Stage 2 mild cognitive impairment (pre-dementia), to
3- Stage 3 more advanced stages of mild, moderate and severe dementia,
the ambiguous “Alzheimer’s disease” statement may raise some confusion about what specific population of patients the drug is equipped to treat.”
It is interesting that the FDA is leaving such a broad range of drug application decisions in the hands of clinicians. This discretionary responsibility, which demands a case-by-case approach to care, will quickly reveal how the field will need to amend its current diagnostic methods and data collection practices. The evolution in clinical diagnostics, such as blood tests for amyloid and tau, will be used in a few years to risk stratify patients and also guide treatment (much like commonly used cholesterol tests today).
Further, genetic testing may also soon become part of a standard of care, especially considering that patients with two copies of the ApoE4 gene are at higher risk for developing side effects from the treatment, which include brain swelling and bleeding. Those patients may be more optimally managed with a more individualized titration schedule and closer monitoring for adverse events with magnetic resonance imaging scans.”
