The 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference in Madrid showcased a range of updates on Alzheimer’s clinical research, revealing both progress and setbacks in the quest for effective treatments. Scientists and drug developers presented findings from Phase 1, 2, and 3 trials, covering disease-modifying biologics, small molecule drugs, and therapies targeting neuropsychiatric symptoms.
Disease-Modifying Alzheimer’s Treatments
Biologics: Antibodies, Vaccines, and Gene Therapies
Eisai's E2814: Eisai presented Phase 1 data on E2814, an anti-tau drug. The two-year trial involving seven participants with mild to moderate genetic Alzheimer’s showed a reduction in disease biomarkers via PET scans. Future studies are planned to assess the drug's effectiveness in slowing cognitive decline.
Roche's Trontinemab: Roche's trontinemab, designed for enhanced blood-brain barrier penetration, was evaluated in a Phase 1/2 trial with 160 participants experiencing MCI or mild to moderate Alzheimer’s. The highest dose led to amyloid reduction below detectable limits in 28 weeks, with less than 10% of participants experiencing ARIA. However, one patient on the second-highest dose experienced a non-ARIA-related brain hemorrhage. The trial is ongoing.
UCB's Beprenemab: UCB presented results from a Phase 2 trial of beprenemab, a tau-targeting antibody, involving 466 participants with MCI or Alzheimer’s. While the drug slowed tau accumulation, it did not demonstrate a significant impact on cognitive decline. Consequently, Roche terminated its agreement with UCB, relinquishing rights to develop and sell the drug.
Vaccinex’s Pepinemab: Vaccinex presented data from its Phase 1/2 trial of pepinemab, an antibody targeting astrocytes, in 50 participants with MCI or mild Alzheimer’s. The drug was safe and well-tolerated, showing potential for slowing cell death and improving brain metabolism in MCI patients. Further trials are yet to be announced.
Lexeo Therapeutics’ LX001: Lexeo Therapeutics presented interim data from its ongoing Phase 1/2 study of LX001, a gene therapy delivering the ApoE2 gene. In 15 patients with MCI or mild to moderate Alzheimer’s, the therapy increased ApoE2 protein production, stabilized amyloid levels, and reduced tau biomarkers in cerebrospinal fluid. The trial is ongoing.
Small Molecule Drugs
Intranasal Insulin and Empagliflozin: A Phase 2 trial explored intranasal insulin and empagliflozin (Jardiance) in 60 individuals with early Alzheimer’s. Both drugs were safe and well-tolerated. Intranasal insulin alone showed a slight improvement in cognitive tests. Larger trials are underway, including participants also taking Leqembi or Kisunla.
Cognition Therapeutics’ CT1812: Cognition Therapeutics presented data from a Phase 2 trial of CT1812, a drug designed to clear toxic beta-amyloid proteins, in 153 participants with mild to moderate Alzheimer’s. While the drug did not slow cognitive decline overall, a subgroup with low levels of a blood-based tau biomarker may have benefited, warranting a Phase 3 trial.
Eli Lilly’s Ceperognastat: Eli Lilly presented data from a Phase 2 trial of ceperognastat, a pill designed to prevent tau tangling, in 327 individuals with early Alzheimer’s. The drug failed to slow cognitive decline at either dosage tested over 124 weeks. Lilly has not announced plans for further trials.
High Dose of DHA: A placebo-controlled trial investigated high-dose DHA supplementation over two years in 365 older adults with dementia risk factors. Overall, supplementation did not affect hippocampal volume or cognitive scores. However, in ApoE4 carriers, cognitive scores were linked to DHA levels, suggesting a potential benefit in this subgroup.
Treatments for Alzheimer’s Symptoms
Small Molecule Drugs for Agitation and Psychiatric Symptoms
Nabilone: Additional data on Nabilone, a cannabinoid drug, indicated that patients with pain, irritability, depressive symptoms, and appetite changes with less cognitive impairment are most likely to benefit from this treatment for agitation.
Dronabinol: A three-week, double-blind, placebo-controlled trial involving 80 Alzheimer’s patients with agitation showed that dronabinol performed slightly better than placebo, with a difference of 0.74 points on a 16-point agitation scale.
Cannabidiol (CBD): A small, double-blinded Phase 2 trial compared CBD against placebo in 15 individuals with Alzheimer’s over six weeks. CBD failed to demonstrate any significant difference in anxiety and agitation among trial participants.
