Our updates from the world of Alzheimer’s and other dementia research and clinical trials from August through October, including the latest news out of this year's CTAD conference.
This past three months in the Alzheimer’s drug development space have seen a new FDA approval for a symptomatic treatment, a couple failed phase 3 trials, more legal drama for drugmaker Cassava Sciences, and a new drug being granted permission for use outside of clinical trials as part of the compassionate use pathway.
This third edition of our quarterly Trials Update — on clinical trials across Alzheimer’s and dementia research — encompasses clinical trials news from these past few months, including new findings presented just a few days ago at the Clinical Trials on Alzheimer’s Disease conference in Madrid, Spain, where our team was reporting on the ground.
Some of the biggest developments:
- At the end of July, the FDA approved Alpha Cognition’s Zunveyl, a new cholinesterase drug with fewer side effects that can treat memory loss in people with mild to moderate Alzheimer’s disease.
- At the end of September, the Securities and Exchange Commission announced that former Cassava Sciences CEO Remi Barbier and former Vice President Lindsay Burns would pay $40 million for making misleading statements about Phase 2 trials of the company’s drug simufilam. Former paid scientific advisor, Hoau-Yan Wang, was charged by the agency with manipulating the Phase 2 trial data.
- At this year’s CTAD conference, we learned that so far, anti-tau drugs are failing to move the needle: UCB’s anti-tau antibody failed to slow cognitive decline in a Phase 2 trial, and an early trial of a small-molecule anti-tau drug developed by Lilly also failed to meet expectations.
Read on for more details on drug updates by drug type. For Trials Updates subscribers, we’ve also pulled together the information on the 76 late-stage drug trials for Alzheimer’s that are currently recruiting — don’t miss that in your Q3 Trial Updates email.
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Explore the updates below:
Disease-modifying drugs for dementia
Biologics:
Antibodies, vaccines, cell infusions and more, designed to stop or slow dementia by clearing biomarkers — i.e. beta-amyloid plaques, tau tangles, or inflammation — from the brain.
Foralumab
Industry sponsored?: Tiziana Life Sciences
Latest trial phase: Approved for Phase 2, not yet recruiting
Next steps: Currently greenlit for moderate Alzheimer’s under the FDA’s “compassionate use” program
Tiziana’s experimental nasal spray, foralumab, is an antibody that stimulates immune cells, called a T-cells, which can prevent excess inflammation in the brain. In 2023, the company received clearance for a Phase 2 trial but has not yet announced when it will start recruiting people with Alzheimer’s for the study. In the meantime, the FDA has granted permission for patients with moderate Alzheimer’s to access foralumab as part of the compassionate use program, outside of clinical trials. This is sometimes granted for investigational drugs when no other treatments are available.
E2814
Industry sponsored?: Eisai
Latest trial phase: Phase 1/2 completed
Next steps: Phase 2/3 trials in the works, not yet recruiting
At CTAD, Eisai presented data from a Phase 1/2 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
Industry sponsored?: No
Latest trial phase: Phase 2 completed
Next steps: A large Phase 3 trial not yet announced
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.
Trontinemab
Industry sponsored?: Roche
Latest trial phase: Phase 1/2 trial ongoing
Next steps: Continuation of current trial
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 an ongoing 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 less than10 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.
Beprenemab
Industry sponsored?: UCB
Latest trial phase: Phase 2 failed to meet its main goals
Next steps: Uncertain following Roche bombshell
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 and functional decline, which was its main stated goal.
Pepinemab
Industry sponsored?: Vaccinex
Latest trial phase: Phase 1/2 completed
Next steps: No announcement for a new trial
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:
Fosgonimeton
Industry sponsored?: Athira
Latest trial phase: Phase 2/3 failed
Next steps: Plans for additional study canceled
This Alzheimer’s drug, which is injected under the skin, is designed to stimulate healthy brain function and protect brain cells from inflammation and neurodegenerative disease. But, Fosgonimeton failed in its 26-week Phase 2/3 trial of 312 participants with mild to moderate Alzheimer’s disease. The company said in a press release that the trial may have been too short to see an effect. The company did not announce whether they will run another drug trial.
AMX0035
Industry sponsored?: Amylyx Pharmaceuticals
Latest trial phase: Phase 2 completed
Next steps: No new trial announced
AMX0035 is a combination of two different drugs that may help prevent cell death and neurodegeneration. The drug received accelerated approval for treating another neurodegenerative disease called amyotrophic lateral sclerosis (ALS), but it was taken off the market after it failed a Phase 3 trial. In August, the company published data from a Phase 2 trial of 95 people with MCI or early Alzheimer’s. The drug lowered the levels of Alzheimer’s biomarkers in cerebrospinal fluid. The company has not yet announced additional clinical trials.
Simufilam
Industry sponsored?: Cassava Sciences
Latest trial phase: Two active Phase 3 trials
Next steps: Phase 2 results in question; Phase 3 results expected by end of year
At the end of September, the Securities and Exchange Commission announced that former CEO Remi Barbier and former Vice President Lindsay Burns would pay $40 million for making misleading statements about Phase 2 trials. Former paid scientific advisor, Hoau-Yan Wang, was charged by the agency with manipulating the Phase 2 trial data. The Department of Justice indicted Wang for fraud in July. The company’s experimental drug simufilam is still in two active Phase 3 trials, with results expected at the end of the year. READ MORE: After Cassava Fraud Indictment, Questioning the Ethics of Simufilam Trial
Intranasal insulin and empagliflozin
Industry sponsored?: No
Latest trial phase: Phase 2 completed
Next step: Larger trials are ongoing
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 trials will include participants taking Leqembi or Kisunla.
CT1812
Industry sponsored?: Cognition Therapeutics
Latest trial phase: Phase 2 failed to meet its main goal
Next step: Data analysis underway
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.
Ceperognastat
Industry sponsored?: Eli Lilly
Latest trial phase: Phase 2
Next step: No announcement for a Phase 3 trial
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.
DHA
Industry sponsored?: No
Latest trial phase: Phase 2 completed
Next step: Further analysis underway
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
LX001
Industry sponsored?: Lexeo Therapeutics
Latest trial phase: Phase 1/2 underway
Next steps: Trial ongoing
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. LEARN MORE: A Peek Into the Future: Gene Therapy for Alzheimer’s
Drugs for treating dementia symptoms
Small-molecule drugs for treating memory-related symptoms, aggression, and agitation in people with Alzheimer’s and other forms of dementia.
Memory symptoms:
Zunveyl
Industry sponsored?: Alpha Cognition
Latest trial phase: FDA approved in July 2024
Next steps: Available in 2025
At the end of July, the FDA approved a pill called Zunveyl. It is a new form of the cholinesterase drug galantamine, which comes with fewer side effects. The drug treats memory loss in mild to moderate Alzheimer’s. It will be available to purchase in 2025.
Montelukast
Industry sponsored?: IntelGenx
Latest trial phase: Phase 2 ongoing
Next steps: Results expected by end of year
Montelukast is a pill that reduces inflammation in the body. It is already approved for treating asthma, allergic rhinitis, and other lung conditions. In July, Intelgenx announced preliminary results of a Phase 2 trial of the drug in 59 participants with mild to moderate Alzheimer’s. So far, the data suggests that a high dose of the drug might treat memory symptoms. The company will update the data after all participants complete the trial later this year.
Nabilone
Industry sponsored?: No
Latest trial phase: Phase 2 completed
Next step: Recruiting for Phase 3 trial
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. LEARN MORE: Here’s What You Need to Know About Cannabis and Cognitive Decline
Dronabinol
Industry sponsored?: No
Latest trial phase: Phase 2 completed
Next step: No additional trials announced
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)
Industry sponsored?: No
Latest trial phase: Phase 2 failed
Next steps: No Phase 3 trial announced
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. READ ON: THC, CBD, & CBN: Can Cannabis Protect the Brain From Alzheimer’s?
