Alzheimer’s treatment: Time for a level-set?

Each September we recognize World Alzheimer’s month, with November being National Alzheimer’s Awareness Month in the U.S. Both occasions mark a time to show support for the millions of people who live with Alzheimer’s disease.¹

• Alzheimer’s disease leads to the progressive loss of many essential mental and physical abilities.²
• Alzheimer’s disease is the 6th leading cause of death among U.S. adults.³
• In 2023, Alzheimer's and other dementias will cost $345 billion in the U.S.⁴

More than 6 million people are living with Alzheimer's dementia in the U.S. Up to 13.8 million may be affected by 2060.⁵

In a recent editorial, 3 geriatric medicine specialists summed up the situation with the current group of anti-amyloid treatments:

“From a more practical standpoint, the modest benefits would likely not be questioned by patients, clinicians, or payers if amyloid antibodies were low risk, inexpensive, and simple to administer. However, they are none of these.”¹⁷[Emphasis added]

Risk, cost and complexity are a good cross-section of the various factors that will affect how many people wind up benefitting from these drugs. Let’s go through them one at a time.

Risk: The side effects

The FDA notes that there are known side effects with the entire class of antibodies targeting amyloid, the most notable of which is amyloid-related imaging abnormalities (ARIA). ARIA-related brain swelling can infrequently lead to seizures, other severe neurological symptoms, or even death.¹⁸

That said, ARIA often displays no symptoms, and usually resolves by itself over time. When symptoms do occur, they are usually mild — a headache or increased confusion.¹⁹

Certain factors, such as, timing, genetics and other brain-related conditions, may increase the risk of ARIA.²⁰  

Anti-amyloid drugs should be used only in the early stages of Alzheimer’s disease.²¹ One reason is that amyloid-lowering therapies may deliver a greater benefit when used earlier in the disease progression.²²

Also related to timing is that serious side-effects from amyloid-related imaging abnormalities may be an unintended result of removing amyloid plaques — doing so may weaken cerebral blood vessels. Therefore, since there is simply less amyloid plaque present in the early stages, the risks associated with removing it should be lower.²³

The gene variant called APOE4 is linked to a higher risk for ARIA. In trials, all 3 amyloid antibody drugs saw a greater risk of ARIA among people who carried copies of this gene.²⁴

Overall, 15% of the Alzheimer's population carries 2 copies of the APOE4 mutation and fall into a high-risk group.²⁵ The genetic-ARIA link is serious enough that the Department of Veterans Affairs has said it won’t routinely cover anti-amyloid treatment for those with 2 copies of APOE4.²⁶

The FDA product label for Leqembi recommends that patients undergo genetic testing for APOE4.²⁷

Anticoagulants are often prescribed in cases of stroke, heart attack and pulmonary embolisms to break down blood clots or prevent clots from forming.²⁸

Many drugs are incompatible with anticoagulants.²⁹ And in trials, using anticoagulants was associated with an increased number of brain hemorrhages in patients taking Leqembi. Therefore, the prescribing information recommends caution when using Leqembi in patients taking anticoagulants.³⁰

Cost: The daunting price of Alzheimer’s treatments 

The wholesale acquisition cost for Leqembi is $26,500 per year. Further, Eli Lilly has said it expects a similar price for donanemab when it is approved.³¹

Medicare will cover 80% of that $26,500. But a 20% co-pay would leave patients paying close to $5,000 out-of-pocket per year. (Different Medicare arrangements would influence these costs.)³²

In addition to the cost of the drugs, patients must adhere to an extensive battery of pre-and-post treatment medical visits, brain scans, laboratory tests and infusion center appointments. That said, treatment costs may actually total approximately $90,000 per year.³³

Worse, analysts warn that these new costs will be hard for the health system to absorb over the short term. The results could include other needed services being displaced, payers sharply restricting access, or that healthcare insurance costs could grow rapidly.³⁴

Of course, total costs will ultimately depend on how many people take the new drugs. As noted, about 1.5 million people have the treatable form of Alzheimer’s disease.³⁵

The makers of Leqembi (Eisai Co. and Biogen Inc.) expect 10,000 people to take the drug by March 2024, and as many as 100,000 by 2026.³⁶ But even at this relatively modest uptake, annual costs for 100,000 treatments would still run to almost $3 billion:

In addition to being expensive, anti-amyloid drugs are very complicated to administer. Depending on utilization, they may require more resources than are currently available.

There continues to be a shortage of neurology specialists who treat Alzheimer’s. The American Academy of Neurology recently found that there may be 28,000 fewer neurologists than needed by 2025.³⁷

Looking specifically at dementia care, a recent study showed that 47% of patients in urban areas had access to neurology care. That drops by nearly 10% for rural areas, where 38% of patients could access neurology care.³⁸