Effectively treating and preventing this common form of dementia will require a cocktail of drugs and a combination of approaches, as well as a drive toward early detection.
Almost two years ago, the FDA approved Eisai and Biogen’s lecanemab (Leqembi) for the treatment of Alzheimer’s disease. The monoclonal antibody is a marked improvement on its predecessor Aduhelm in that it was the first drug approved for standalone use that could interrupt the progression of the disease rather than just treat symptoms, and it was hailed as a turning point in treatment.
Lecanemab is far from a silver bullet. It requires biweekly infusions in a medical setting, making it both costly and time-consuming. It also has a list of side effects that run the gamut from fever and chills during infusion to dizziness, confusion and brain bleeds.
But it is an important starting point. Doctors now have more tools at their disposal, as imperfect as they may be, and patients have more hope of an eventual treatment.
That hope can act as a catalyst for future progress, which I’ve seen firsthand in my work as a principal investigator with Velocity Clinical Research, a network organization that recruits patients and runs clinical trials for compounds to treat Alzheimer’s and other conditions. In clinical trial settings, we do see participants seeking a Hail Mary, but more often than not, our trial participants are motivated to contribute to a better outcome for patients in the future. Advances like lecanemab, rightly highly publicized, give them hope that a cure will one day be possible. That cure is likely to come not via a single drug, but a combination of cutting-edge medications, some of which have yet to be developed.
Why a Cocktail?
The race to cure Alzheimer’s is made more difficult by the fact that we still don’t fully understand the risk factors and mechanism of the disease. Amyloid proteins have been associated with it since day one, but the involvement of the tau protein is a relatively new discovery, and we’ve yet to find out why some patients have inflammation in the brain, or how genetic markers contribute to the disease. With every new discovery, we create more possibilities for treatment.
Monoclonal antibody treatments like lecanemab are important—they’re needed to break down amyloid proteins—but they aren’t the only emerging Alzheimer’s treatment. I think it’s likely that eventually they’ll become a small part of an overall treatment plan. We’ll use a drug like lecanemab to eliminate the amyloid, alongside an anti-inflammatory or a medication to block β-secretase, the enzyme that produces amyloids.
This cocktail of drugs mirrors the treatment protocols developed for leukemia and AIDS, but it’s still short on ingredients. We must develop more drugs that interrupt the disease rather than treat symptoms.
Eli Lilly’s donanemab (Kisunla), approved almost exactly a year after lecanemab, is another important milestone. It has a similar effect, targeting and breaking down amyloid plaques, but only needs to be administered monthly and until those plaques are removed, making it cheaper and less involved than lecanemab. Initial research showed it can slow disease progression, particularly among early-stage patients. (Velocity Clinical Research was involved in the development of donanemab.)
Prevention vs. Cure
The emergence of a treatment that works on patients with less advanced disease is another key milestone. The ability to slow progression before symptoms become advanced is life-changing for patients and their families. However, it does put more pressure on healthcare providers to notice abnormalities early. This is a tall order, given that most Alzheimer’s research to date has focused on older patients with advanced symptoms.
This development emphasizes the need to extend research protocols to include younger patients with risk factors. A donanemab study of presymptomatic patients is currently underway, involving participants who have yet to experience Alzheimer’s symptoms but who have genetic markers or PET scan abnormalities that mark them as higher risk. Results are years away, but it’s another critical step in developing a preventive treatment.
Clinical researchers aren’t the only ones now recognizing the need to advance early detection. The U.S. government committed an additional $100 million to Alzheimer’s and dementia research earlier this year, with a focus on prevention, early detection and diagnosis.
Lecanemab’s Legacy
The approval of lecanemab, a drug that could modify the disease, was a huge leap forward in the treatment of Alzheimer’s. It was also the starting point for a growing momentum that has given patients and caregivers hope, preceded the development of another disease-modifying treatment in donanemab and is already attracting more government funding.
For those of us in the field, the hope is that this momentum will lead to more breakthroughs, give physicians and patients more tools and ultimately deliver the building blocks for a cocktail to prevent Alzheimer’s.
