With the Food and Drug Administration’s full stamp of approval in hand, Leqembi (lecanemab) is poised to catapult us into a new era of treatment for Alzheimer’s disease. And now that the donanemab trial data are out, there’s another antiamyloid drug waiting in the wings.
To finally have true disease-modifying therapies for Alzheimer’s disease is a massive step forward for a field that’s been plagued with disappointment. But these drugs come with serious concerns and unknowns. They will require complex decision-making, putting doctors, patients, and their families in a medical quandary.
Striking the right balance between cautious optimism and realistic expectations will be a formidable challenge.
Managing patient and family expectations
These drugs are no magic bullet. They slow down the dementia’s progression, buying patients more time (on the order of months) before they begin to experience significant worsening. We’ll need a lot more information from research and clinical experience before we can understand how meaningful that treatment effect is. Right now, it is unclear whether eligible patients and their families will even perceive tangible differences.
In the CLARITY-AD trial, participants on lecanemab experienced a 27% slowing in the rate of cognitive decline over 18 months. Donanemab was shown to slow decline in memory and cognition by about 35% over the same time frame in the TRAILBLAZER-ALZ 2 trial. That translates to more time for patients and their families to enjoy independence, maintain normal life, and stave off the most distressing parts of the disease.
But what happens after 18 months of treatment – will the treatment effect magnify or dissipate? How much time are we really buying in the long run? Counseling patients and their families is made all the more difficult when the answers to important questions like these remain to be seen.
Only a sliver of Alzheimer’s patients are current candidates
The fact is that most patients living with Alzheimer’s disease will not qualify for treatment with these drugs. Lecanemab is approved for people with early-stage disease, meaning their dementia is mild or they have mild cognitive impairment, which is a precursor to full-blown Alzheimer’s disease. Of the 6 million people in the United States living with Alzheimer’s, about 1.5 million are estimated to fall into that category. We can expect to see a similar qualifier for donanemab if it receives FDA approval, especially because that trial suggested a more pronounced treatment effect for patients in the earliest stages of the disease.
Even if a patient hits the sweet spot where they have just enough cognitive impairment, but not too much, they aren’t technically therapeutic candidates until prerequisite testing confirms amyloid protein accumulation in the brain via PET scan or cerebrospinal fluid analysis.
Even then, the FDA’s boxed warning for lecanemab recommends that patients undergo genetic testing for the apo E4 mutation to identify those at a particularly high risk for severe adverse effects including brain bleeding and swelling. This recommendation is not unreasonable considering that 15% of the Alzheimer’s population has two copies of the apo E4 mutation and fall into that high-risk group.