New findings presented at 2024’s CTAD conference in Madrid, where Being Patient gathered the latest updates on Alzheimer’s clinical research.
At the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference in Madrid, Spain, scientists and drug development companies gathered to report on recent successes (and failures) as they push the boundaries of Alzheimer’s research in clinical research.
Being Patient founder Deborah Kan was on the ground in Madrid, while reporter Simon Spichak weathered the conference’s virtual experience, including dozens of presentations on findings from Phase 1, 2 and 3 trials. The newsroom’s CTAD reporting transforms dense data and scientific jargon into meaningful updates on the state of disease-modifying biologics, small molecule drugs, and therapies targeting neuropsychiatric symptoms in Alzheimer’s.
Read our highlights below, and find these and more of the latest news in clinical trials from throughout Q3 in our free, quarterly Trials Update newsletter, out tomorrow.
Disease-modifying Alzheimer’s treatments
Biologics: Antibodies, vaccines, cell infusions and more
Eisai’s E2814. At CTAD, Eisai presented data from a Phase 1 study of its anti-tau drug, E2814. In a two-year trial, seven trial participants in the mild to moderate stages of genetic Alzheimer’s received the treatment via infusion. According to PET scans, it appeared to reduce levels of disease biomarkers. Future studies will test the drug’s effectiveness.
Nilotinib. Nilotinib is an antibody used to slow cancer growth. Early studies in cells and mice suggest it could also protect the brain. At CTAD, researchers presented data from a Phase 2 trial involving 43 participants with Lewy body dementia. The drug was safe and well-tolerated. Participants in both groups declined over the study, but those receiving the drug declined by 2.8 points less on a 90-point dementia scale. These results, according to researchers, warrant a large Phase 3 trial.
Roche’s trontinemab. The anti-amyloid drug trontinemab is designed to get past the blood-brain barrier more easily than the anti-amyloid mab drugs in use so far, meaning treatment requires lower doses than other mabs. At CTAD, researchers presented data from a Phase 1/2 trial testing different doses in 160 participants with MCI or mild to moderate Alzheimer’s. The highest dose reduced amyloid below detectable limits in 28 weeks of treatment with <10 percent of participants experiencing the side effect of ARIA, as compared to 21.5 percent in the Leqembi trial and 37 percent in the Kisunla trial. Roche reported one patient receiving the second-highest dosage died from a non-ARIA-related brain hemorrhage. The study is continuing to test the drug.
UCB’s beprenemab. Beprenemab is an experimental tau-targeting antibody for Alzheimer’s. Roche had purchased exclusive rights from UCB to develop and sell the drug, contingent on UCB completing a Phase 2 study. And right before UCB’s CTAD presentation, Roche for some reason lost confidence in the deal and terminated that agreement, giving up $120 million. In that randomized Phase 2 trial, 466 people with MCI or Alzheimer’s received one of two dosages of the drug or placebo for 18 months. The drug appeared to slow tau accumulation with few side effects but did not slow cognitive decline.
Vaccinex’s pepinemab. Pepinemab is an infusion antibody that binds to a protein found on astrocytes, the brain’s supportive cells, to boost brain metabolism and prevent cell death. At CTAD, Vaccinex presented data from its 50-participant, year-long Phase 1/2 trial, which pitted the drug against a placebo for treatment of MCI or mild Alzheimer’s. The drug was safe and well-tolerated, and it showed signs that it slowed cell death and improved brain metabolism in people with MCI. The company has not yet announced another trial for Alzheimer’s.
Small molecule drugs
Intranasal insulin and empagliflozin. A small, four-week-long Phase 2 trial tested two repurposed drugs: intranasal insulin and a diabetes drug called empagliflozin (brand name: Jardiance) in 60 people with a clinical diagnosis of early Alzheimer’s. Researchers presented data at CTAD showing both drugs were safe and well-tolerated. The insulin alone, but not Jardiance or a combination of insulin and Jardiance was associated with a small improvement in a cognitive test. Larger, longer trials are ongoing. Some of the future trial will include participants taking Leqembi or Kisunla.
Cognition Therapeutics’ CT1812. CT1812 is a small molecule drug that helps clear toxic beta-amyloid proteins from the brain. At CTAD, the company presented data from a Phase 2 trial involving 153 participants with mild to moderate Alzheimer’s who received either the treatment or placebo over six months. The drug didn’t slow cognitive decline overall. However, a subgroup of participants with low levels of a blood-based tau biomarker may have benefited. The company said they will need a Phase 3 trial to confirm whether the drug actually worked.
Eli Lilly’s ceperognastat. Ceperognastat is a pill designed to prevent tau from tangling in the brain. Lilly presented data from a Phase 2 trial of 327 people with early Alzheimer’s, where researchers compared two dosages of the pill against placebo over 124 weeks. But in either dosage, the drug failed to slow cognitive decline. Lilly has not yet announced whether they’ll try again with another trial.
High Dose of DHA. DHA in an omega-3 fatty acid found in fish oil, which is known to benefit brain health in multiple ways. At CTAD, researchers presented data from a placebo-controlled trial that tested whether two years of supplementation with a high dose of DHA could delay the onset of Alzheimer’s. The researchers recruited 365 older Americans with at least one dementia risk factor who weren’t getting a lot of DHA from their diet. Overall, supplementation didn’t affect the volume of the hippocampus (the memory region of the brain) and did not have an effect on cognitive scores. However, in people with the ApoE4 gene, cognitive scores were linked to DHA levels; even though DHA supplementation wasn’t linked to improved cognitive scores, this link suggests that DHA might be important. The researchers are still going through the data to see whether some people might benefit from DHA supplements and what genetics has to do with it.
Gene therapies
Lexeo Therapeutics’ LX001. LX001 is a gene-editing therapy. It inserts a copy of ApoE2 gene, via intravenous injection, into the brain, to counteract the effects of Alzheimer’s risk gene ApoE4. At CTAD, the company presented data from the ongoing Phase 1/2 study, which treated 15 patients with MCI or mild to moderate Alzheimer’s with four different dose regimes. Participants treated with the gene therapy did indeed start producing ApoE2 protein and showed a stabilization in amyloid levels and a reduction in tau biomarkers in the cerebrospinal fluid. The trial is still ongoing.
Treatments for Alzheimer’s symptoms
Small molecule drugs for agitation and psychiatric symptoms
Nabilone. Nabilone is a cannabinoid drug that works like one of the active molecules found in cannabis, called tetrahydrocannabinol. Nabilone is prescribed to treat nausea, vomiting, and lack of appetite that might occur after chemotherapy. A previous study of 35 people with Alzheimer’s found that 8 weeks of treatment is effective for treating agitation. Researchers at CTAD presented more data from this study, finding that patients with pain, irritability, depressive symptoms, and appetite changes with less cognitive impairment are most likely to benefit.
Dronabinol. Dronabinol, which is on the market for treating nausea and vomiting caused by cancer medicines under the brand names of Marinol and Syndros, is another drug designed to mimic the effects of THC. In a study presented at CTAD, researchers conducted a three-week-long, double-blind, placebo-controlled trial involving 80 Alzheimer’s patients with agitation. Dronabinol did a bit better at treating agitation than the placebo, with a difference of 0.74 more points on a 16-point scale.
Cannabidiol (CBD). CBD is one of the two major active molecules found in cannabis. Some studies suggest CBD could reduce anxiety levels. Would this hold for people with Alzheimer’s? Researchers presented results from a small, double-blinded Phase 2 trial that pitted CBD against a placebo in 15 people with Alzheimer’s, over six weeks. But ultimately, CBD failed to make any difference in anxiety and agitation in trial participants.
Reporting by Simon Spichak
