Healthcare professionals are at the forefront of patient care and management, particularly for those affected by debilitating diseases like Alzheimer's. The role they play in understanding how to handle care for these patients is ever-evolving, especially with the latest advancements in Alzheimer’s drugs that have been recently approved by the FDA. However, understanding the implications and appropriate clinical applications is crucial as we navigate these groundbreaking yet complex developments in Alzheimer's care, ensuring that patients receive the most informed and effective treatment possible.
In the past three years, three disease-modifying Alzheimer’s disease (AD) drugs have been FDA-approved, including Aducanumab in 2021, Lecanemab in 2023, and Donanemab in 2024. All three of these drugs belong to a class of drugs called anti-amyloid monoclonal antibodies that target and clear amyloid, a protein that aggregates in the brains of individuals with AD.
These drugs are among the first to be approved for AD in decades and highlight efforts by the National Institute of Health and pharmaceutical companies to develop novel drugs that combat a disease that affects approximately 1 in 9 adults 65 and older. All three drugs were developed based on the amyloid hypothesis, which suggests that the accumulation of amyloid plaques in the brain causes AD. Therefore, drugs that clear amyloid are likely to slow down or prevent AD progression.
While these drugs have been shown to clear amyloid efficiently and quickly, the amyloid hypothesis is controversial, and whether amyloid truly causes AD is contested. Additionally, despite accelerated FDA approval, aducanumab was discontinued as an AD treatment in 2024 by Biogen (the drug’s manufacturer) due to a lack of clear evidence of efficacy and challenges with payor coverage.
Researchers, clinicians, and patient advocacy groups are debating the benefits and risks of taking Lecanemab and Donanemab, which both require a long course of treatment, monthly infusions and brain imaging. Four areas of controversy include:
Efficacy: In both the Lecanemab and Donanemab clinical trials, significant cognitive benefits were observed when comparing treatment to placebo; however, these differences likely fall below the minimal clinically important difference (MCID) threshold. Considering the risks of treatment, cost, administrative and clinical resources required, as well as the intensive treatment course, the balance between benefits and risk for patients needs to be weighed carefully.
Brain swelling: Between 12-35% of patients in the treatment arm of both trials experienced brain swelling and bleeding (termed ARIA). Serious symptoms of ARIA include headaches, seizures and delirium. Currently, drug manufacturers have not disclosed the clinical effects of patients on treatment who experienced ARIA during the clinical trials.
Brain shrinkage: In both trials, patients in the treatment arm compared to the placebo experienced brain atrophy. This finding is consistent with results from several anti-amyloid drugs. Brain shrinkage is associated with the progression/ worsening in AD not alleviation as would be expected in the treatment arm of a beneficial, disease modifying treatment.
Cost: The total cost of treatment for Lecanemab (and likely similar for Donanemab) is approximately $82,500 per patient per year, incorporating the drug cost and required genetic testing, brain scans, etc. Considering the drugs’ observed efficacy, these costs have been determined to be not cost effective compared to the current standard of care.
As drug manufacturers roll out both Lecanemab and Donanemab into clinical practice, the challenges of treating patients, including appropriately communicating risks, navigating complicated Medicaid, Medicare, and private insurance payment models, and monitoring patients for serious side effects, will become clearer. Phase 4 trials/post-marketing surveillance will hopefully provide additional information on the long-term risks and benefits of both drugs in the general population.
So, for those caring for Alzheimer’s patients–whether families or healthcare professionals—understanding the benefits and risks of these therapies, from managing potential side effects to navigating the intricacies of insurance coverage, is crucial. This knowledge equips caregivers to make informed medical decisions, informs the consideration of timely and appropriate interventions, and enhances the overall quality of care. By being well-informed, everyone can better advocate for their patients or loved ones, develop appropriate and evidence-based treatment plans, and improve health outcomes. Ultimately, this comprehensive understanding fosters a collaborative approach to managing Alzheimer's disease, optimizing patient well-being and quality of life.
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