Recent updates from Alzheimer's disease clinical trials reveal both progress and setbacks in the development of novel therapies. Data presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference in Madrid, Spain, highlighted the latest findings on disease-modifying drugs, including biologics, small-molecule drugs, and gene therapies.
Anti-Tau Therapies Show Mixed Results
Eisai presented data from a Phase 1/2 study of its anti-tau drug, E2814. The two-year trial involved seven participants in the mild to moderate stages of genetic Alzheimer’s disease who received the treatment via infusion. PET scans indicated a reduction in disease biomarkers. Further studies are planned to assess the drug’s effectiveness in larger populations.
However, not all anti-tau therapies have shown promise. Roche terminated its agreement with UCB for beprenemab, an experimental tau-targeting antibody. This decision followed the Phase 2 trial results, which demonstrated that while the drug appeared to slow tau accumulation, it did not slow cognitive and functional decline, the trial's primary endpoint. The randomized Phase 2 trial included 466 participants with mild cognitive impairment (MCI) or Alzheimer’s disease, who received one of two dosages of the drug or a placebo for 18 months.
Amyloid-Targeting Drug Shows Promise
Roche presented data from an ongoing Phase 1/2 trial of trontinemab, an anti-amyloid drug designed to cross the blood-brain barrier more effectively than existing monoclonal antibodies. The trial included 160 participants with MCI or mild to moderate Alzheimer’s disease. Interim results showed that the highest dose reduced amyloid levels below detectable limits in 28 weeks of treatment, with less than 10% of participants experiencing ARIA (amyloid-related imaging abnormalities), a side effect commonly associated with anti-amyloid therapies. For comparison, the Leqembi trial reported ARIA in 21.5% of participants, while the Kisunla trial reported 37%.
Small Molecule and Combination Therapies
Nilotinib, an antibody used to slow cancer growth, was evaluated in a Phase 2 trial involving 43 participants with Lewy body dementia. While the drug was found to be safe and well-tolerated, participants in both the treatment and placebo groups declined over the study period. However, those receiving nilotinib declined by 2.8 points less on a 90-point dementia scale, suggesting a potential benefit that warrants further investigation in a larger Phase 3 trial.
A small Phase 2 trial also explored the potential of repurposed drugs for early Alzheimer’s disease. Intranasal insulin and empagliflozin, a diabetes drug, were tested in 60 people with early Alzheimer’s. The results indicated that insulin alone, but not empagliflozin or a combination of both, was associated with a small improvement in cognitive test performance. Larger, longer trials are ongoing to further investigate these findings, including studies involving participants taking Leqembi or Kisunla.
Other Notable Updates
- Foralumab: Tiziana Life Sciences' nasal spray, foralumab, an antibody that stimulates T-cells to prevent excess brain inflammation, has been granted permission for compassionate use in patients with moderate Alzheimer’s disease.
- Simufilam: Cassava Sciences' experimental drug, simufilam, remains in two active Phase 3 trials, with results expected by the end of the year, despite ongoing investigations into alleged data manipulation in earlier trials.
- LX001: Lexeo Therapeutics presented data from an ongoing Phase 1/2 study of LX001, a gene-editing therapy that inserts a copy of the ApoE2 gene into the brain to counteract the effects of the Alzheimer’s risk gene ApoE4. The trial showed that participants treated with the gene therapy started producing ApoE2 protein and experienced a stabilization in amyloid levels and a reduction in tau biomarkers in the cerebrospinal fluid.
