Three potential disease-modifying treatments for early-stage Alzheimer's disease – remternetug, buntanetap, and semaglutide – are showing promise in clinical trials, offering renewed hope for slowing cognitive decline. These drugs target different aspects of the disease pathology, including amyloid plaques, tau protein, and insulin resistance in the brain.
Remternetug: Enhanced Amyloid Clearance
Remternetug, developed by Eli Lilly, is a second-generation immunotherapy targeting amyloid plaques, similar to lecanemab and donanemab. A Phase 3 trial (TRAILRUNNER-ALZ 1) is underway to assess its effectiveness and safety in individuals with mild Alzheimer's disease. Early data suggests that remternetug may clear amyloid more rapidly than donanemab. In a small study, 75% of participants treated with remternetug had amyloid cleared from their brains after 6 months, compared to 72% after 18 months with donanemab. The trial also compares intravenous administration to subcutaneous injections, aiming for a more practical and potentially more effective delivery method. However, some participants experienced brain swelling or bleeding, highlighting the need for careful monitoring.
Buntanetap: Targeting Amyloid Precursor Protein and Tau
Buntanetap, under investigation by Annovis Bio, reduces the production of amyloid precursor protein (APP), which is processed into the toxic form of amyloid. A recent trial demonstrated improvements in memory and thinking scores after 12 weeks of treatment with buntanetap in participants with early-stage Alzheimer's disease. The drug also reduced levels of tau protein in the blood, another key factor in Alzheimer's pathology. Importantly, no serious side effects were observed. Annovis Bio is planning a larger, 18-month Phase 3 study to confirm these findings and assess buntanetap's ability to slow disease progression.
Semaglutide: Addressing Insulin Resistance
Semaglutide, marketed as Ozempic and Wegovy, is primarily used for managing type 2 diabetes and aiding in weight loss. Observational studies suggested a reduced risk of dementia in individuals taking similar drugs for diabetes, prompting clinical trials to explore semaglutide's potential in treating Alzheimer's disease. Semaglutide mimics a natural hormone, stimulating insulin production and reducing blood sugar levels. Researchers hypothesize that this mechanism may also benefit the brain by improving insulin sensitivity and interacting with receptors involved in learning and brain cell protection. Novo Nordisk is conducting multiple clinical trials to assess semaglutide's safety and impact on gene expression, memory, and thinking abilities in individuals with Alzheimer's disease, including those with cerebrovascular conditions. Results from these trials are expected by September 2025.
Access and Future Availability
Currently, remternetug, buntanetap, and semaglutide are experimental medicines and not available outside of clinical trials in the UK. While lecanemab and donanemab have been approved for use in the UK, they have not been recommended for NHS funding due to cost-effectiveness concerns. The Medicines and Healthcare Products Regulatory Agency (MHRA) will evaluate the safety and efficacy of remternetug, buntanetap, and semaglutide before potential approval. The National Institute for Health and Care Excellence (NICE) will then assess their cost-effectiveness for NHS availability. These drugs are primarily intended for individuals with mild cognitive impairment (MCI) or early-stage Alzheimer's disease, as clinical trials have not demonstrated benefits for those in later stages of the disease or with other forms of dementia.
