This week, the FDA approved aducanumab (ADUHELM), a monoclonal antibody which is the first drug approved by the FDA for its ability to reduce plaque burden in Alzheimer's Disease (this and other biomarker-based approvals are generally "accelerated approvals.") Find a range of links here.
The labeling is very broad - "indicated for the treatment of Alzheimer's disease" without explicit biomarker, age, or severity classifications. Since all ADUHELM clinical study patients were PET-scan positive for beta-amyloid, insurers might require that for drug therapy. Alternatively, there is a CSF amyloid test under FDA review (press releases from Fujirebio), although there's no mention of that in the FDA labeling.
There's one other biomarker that has garnered less media this week - Apo E4. ADU studies consistently found that patients who were ApoE4-positive, a minority of the natural population, were twice as likely to develop ARIA (drug-induced brain changes.). And in some of the studies, ApoE4-status was used to set initial dose of drug for safety reasons.
Generally, Medicare contractors have a block against testing ApoE4 status,[*] and the usage in the Medicare population has been very low [**]. I haven't seen any discussion of whether ApoE4 status will be considered a standard of care for an Alzheimer evaluation when ADUHELM therapy is one of the central considerations.
Most private payers block ApoE4 payments, according to an April 2021 study of payer policies here.
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* Copy of ApoE article here. ApoE genetics and CSF Tau studies are mentioned in labeling; FDA is known to be reviewing some CSF AMY tests.
** ApoE4 (2*, 3*, 4*) is a Tier 2 code (81401) suggesting it is so low in clinical frequency that it has never been elevate to a Tier 1 code.
