Latest 'Breakthrough' Drugs: The Infusion Era
The most discussed and recently approved treatments for early-stage Alzheimer's disease are disease-modifying therapies (DMTs) that target amyloid plaques in the brain. Unlike traditional medications that only manage symptoms, these new drugs aim to address the underlying pathology of the disease. It is crucial to understand that these therapies are not oral pills; they are given via intravenous (IV) infusion.
Donanemab (Kisunla)
Approved by the FDA in July 2024, donanemab is an IV infusion administered monthly. It works by targeting a specific, modified form of amyloid beta that has already clumped into plaques. Clinical trials showed it slowed cognitive and functional decline by an estimated 29% over 18 months, with nearly half of participants able to stop treatment after 12 months once plaques were cleared. A boxed warning notes potential side effects including brain swelling and microbleeds.
Lecanemab (Leqembi)
Lecanemab received traditional FDA approval in July 2023 for early Alzheimer's. This monoclonal antibody is delivered via a bi-weekly IV infusion and targets amyloid beta protofibrils, slowing cognitive decline by 27% compared to placebo in trials. Like donanemab, it carries a boxed warning for similar brain swelling and microbleeds.
The Quest for an Oral Alzheimer's Pill
While infusions are a significant step, the search for a convenient oral medication continues for improved accessibility. Several oral candidates are in development:
- ALZ-801: This oral small molecule targets amyloid plaque formation, particularly in those with two copies of the APOE4 gene. A new drug application is expected soon.
- Blarcamesine (ANAVEX®2-73): This oral small molecule acts on sigma-1 receptors to potentially improve cell signaling, reduce inflammation, and help clear misfolded proteins.
- Remternetug: Originally an IV anti-amyloid therapy, research is exploring a potential subcutaneous injection for easier home administration.
- Semaglutide: This existing oral medication for diabetes and weight loss is being investigated for its potential to slow Alzheimer's progression, with key trial results anticipated in late 2025 and 2026.
Comparison of Prominent Alzheimer's Treatments
| Feature | Donanemab (Kisunla) | Lecanemab (Leqembi) | ALZ-801 | Blarcamesine | Remternetug | Semaglutide |
|---|---|---|---|---|---|---|
| Administration | IV Infusion | IV Infusion | Oral pill | Oral pill | IV, potential subcutaneous | Oral pill |
| Primary Target | Amyloid plaques | Amyloid protofibrils | Amyloid aggregation | Sigma-1 receptors | Amyloid (2nd-gen) | GLP-1 receptors |
| Current Status | FDA Approved (July 2024) | FDA Approved (July 2023) | Phase 3 Trials | Phase 3 Trials | Phase 3 Trials | Phase 3 Trials |
| Key Feature | Can be discontinued after plaque clearance | Continuous bi-weekly administration | Oral, designed for APOE4 carriers | Novel mechanism, targets cell signaling | Potential for at-home injection | Repurposed diabetes drug, oral format |
The Path Forward: Hope on the Horizon
The approval of donanemab and lecanemab are significant advancements, offering the first disease-modifying options for early Alzheimer's. While administered via infusion and having modest effects, they validate targeting underlying disease mechanisms. The development of oral pills and repurposed drugs like ALZ-801 and semaglutide offers hope for more accessible and potentially effective future treatments.
While a cure is not yet available and safety concerns exist, progress in the treatment pipeline is promising. Future treatments could be safer, more effective, and potentially available as a pill. Patients and caregivers should consult healthcare professionals to discuss eligibility, risks, and benefits. More information on trials is available from resources like the National Institute on Aging.
