From the Guidelines
Yes, there are several new pharmaceuticals for Alzheimer's disease, including Lecanemab (Leqembi) and Aducanumab (Aduhelm), which have been approved by the FDA for the treatment of early symptomatic Alzheimer's disease. These medications are monoclonal antibodies administered via intravenous infusion, typically every two weeks, and have shown modest benefits in slowing cognitive decline by approximately 27% over 18 months in early-stage Alzheimer's patients 1. They work by binding to and removing amyloid beta plaques, which are believed to contribute to neuronal damage in Alzheimer's disease. However, they can cause side effects including brain swelling (ARIA-E) and microhemorrhages (ARIA-H), requiring regular MRI monitoring during treatment.
Key Points
- Lecanemab and Aducanumab are the first disease-modifying treatments (DMTs) for Alzheimer's disease, approved by the FDA for early symptomatic AD, including mild cognitive impairment (MCI) or mild dementia caused by AD 1.
- Biomarker confirmation of amyloid pathology is required before initiating these treatments, highlighting the need for accurate biomarker-based diagnosis of AD in people with MCI and mild dementia 1.
- Donanemab is another anti-amyloid antibody that has shown promising results in clinical trials but is not yet FDA approved 1.
- These new treatments represent a shift toward disease-modifying therapies rather than just symptom management, though their benefits are modest and they are generally limited to early stages of the disease.
Treatment Considerations
- The use of these medications should be considered in the context of the individual patient's disease stage, overall health, and potential benefits and risks.
- Regular monitoring for side effects, including brain swelling and microhemorrhages, is essential during treatment with Lecanemab and Aducanumab.
- The development of blood biomarker tests for the detection of AD pathology has improved the diagnosis and management of Alzheimer's disease, enabling earlier initiation of treatment when it is likely to be most effective 1.
From the Research
Current Pharmaceutical Landscape for Alzheimer's Disease
- The current competitive landscape in AD consists of symptomatic treatments, with six approved medications: three AChEIs (donepezil, rivastigmine, and galantamine), one NMDA-R antagonist (memantine), one combination therapy (memantine/donepezil), and GV-971 (sodium oligomannate, a mixture of oligosaccharides derived from algae) only approved in China 2.
- Recently, Aducanumab, the first disease-modifying therapy (DMT) has been approved for AD, and several DMTs are in advanced stages of clinical development or regulatory review 2.
New Therapeutic Agents in Development
- Researchers are exploring new targets and developing novel therapeutic agents for the treatment of AD, including those acting on amyloids, tau proteins, and neuroinflammation 3.
- Nanoparticle-based drug delivery systems have shown promising potential as precision medicines that can effectively penetrate the blood-brain barrier and enhance the targeting ability of numerous drugs 4.
- New therapeutics beyond amyloid-β and tau are being developed, including those that regulate neurotransmitters, inflammation, lipid metabolism, autophagy, microbiota, circadian rhythm, and disease-modified genes for AD 5.
Challenges and Future Directions
- Despite the tremendous improvement in our understanding of the underlying pathophysiology of AD, only aducanumab was approved by FDA for the treatment of AD in 18 years, highlighting the need for novel therapeutic strategies 3.
- A critical review of the disease-modifying therapy pipeline for Alzheimer's disease is needed to address the significant unmet need for a better understanding of the AD pathogenesis and the exploration of alternative etiologies and therapeutic effective disease-modifying therapies strategies for AD 2.
- More clinical trials are required to prove the effectiveness of current and emerging therapeutic agents for AD 6.