We finally have new Alzheimer’s drugs. How do we decide who gets them?

The recent FDA approval of Leqembi, the latest anti-amyloid drug, is undoubtedly a breakthrough for the field, providing a new way to slow the advancement of mild cognitive impairment or early-stage Alzheimer’s disease. As a practicing geriatrician who has treated Alzheimer’s patients for more than 40 years and the co-founder and chief science officer at the Alzheimer’s Drug Discovery Foundation, I have never been more optimistic about our potential to transform how we treat and diagnose patients.

Hundreds of thousands of patients are expected to be prescribed Leqembi in the coming years, according to the drugmakers Eisai and Biogen. However, for Leqembi and other anti-amyloid therapies to become the standard of care, we need to accelerate the development, awareness, and implementation of novel diagnostics and biomarkers. As a field, it is our obligation to ensure every patient given a drug qualifies for it, and that requires accessible and affordable diagnostics. To optimize care efficiency and improve the patient experience, it is vital that we reconsider our approach to developing Alzheimer’s diagnostics and treatments.

Currently a definitive Alzheimer’s diagnosis relies either on an invasive and costly PET amyloid scan or a spinal tap to confirm the presence of amyloid in the brain. These technologies present significant barriers for many patients, and without these tools, patients may receive a misdiagnosis, raising concern about our ability to identify the subset of patients who will most benefit from anti-amyloid drugs.

Novel diagnostics offer a promising alternative. We now have a blood test on the market from C2N Diagnostics, which analyzes a patient’s blood for beta-amyloid. (The Alzheimer’s Drug Discovery Foundation provided early seed funding for C2N’s blood test.) While this blood test alone cannot provide a confirmed diagnosis, it is already serving as a first-line diagnostic tool before referring patients to the more invasive and costly scans.

C2N is not alone in this space — there are several other blood tests in development as well as retinal scans and digital tools that will allow us to accurately detect and diagnose the disease before symptoms present. With the addition of these new resources, we have the potential to revolutionize the way patients are diagnosed, leading to more timely treatment interventions to slow the progression of Alzheimer’s.

Aside from diagnostic benefits, biomarkers are also the determining factor between a well-powered clinical trial and an underpowered one. They are critical to patient enrollment, providing a less burdensome and costly way to enroll patients in clinical trials as well as help to measure target engagement of a drug. Prior to the approval of the amyloid PET scan in 2012, many people were misdiagnosed with Alzheimer’s as we did not have the tools to confirm the presence of amyloid plaques in the brain. Independent research found that nearly 20% of people enrolled in previous Alzheimer’s clinical trials had a negative amyloid PET scan, suggesting their diagnosis was incorrect.

Unsurprisingly, this inhibited our ability to run rigorous clinical trials and test the effectiveness of new therapies. Blood tests both currently available on the market and in development will offer ways to reduce the costs and improve the accuracy of screening, enrollment, and monitoring of patients in trials.

Nevertheless, current beta-amyloid and phospho-tau biomarkers, though significant, represent only a fraction of the Alzheimer’s story. We have identified seven other pathways centered around the biology of aging that contribute to the onset of the disease, emphasizing the need to develop corresponding biomarkers focused on these pathways. Currently, more than 75% of the drugs in clinical development are exploring novel targets, indicating a broadening in our understanding of Alzheimer’s and the field’s focus. As researchers explore these other pathways associated with aging, such neuroinflammation, metabolic disturbances, and vascular dysfunction, we must also advance the pipeline of diverse biomarkers. Otherwise, progression in Alzheimer’s research will be hindered, potentially delaying the next breakthrough.

Leqembi’s approval marks the beginning of a transformative era and highlights the need to reframe our approach from developing and commercializing new drugs and biomarkers in silos, and instead to developing them in parallel. This will be crucial to ensure that the next class of drugs reaches patients sooner, helping to bridge the gap between FDA approval of a drug and rollout. As more biomarkers become available, we will move closer to the day when we can match the right patients with the right drugs at the right time, leading to precision medicine. Ultimately, it will take a combination therapy approach, similar to those used in cancer treatment, to slow down the progression of the disease and stop Alzheimer’s in its tracks.

Howard Fillit, MD, is the co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation.