While news about anti-amyloid drugs like Leqembi and donanemab have been hogging the spotlight, drug companies with other treatment approaches have made major announcements.
The monoclonal antibody drugs targeting the brain’s amyloid plaques dominated the news cycle in 2023. Eisai and Biogen’s Leqembi was approved by the FDA — first through the accelerated approval pathway in January and full approval in July — for treating mild cognitive impairment and early Alzheimer’s disease. The drug cleared out pathological beta-amyloid plaques in the brain and slowed cognitive decline a bit. However, some clinicians aren’t sure whether these changes are noticeable and whether they outweigh some of the risks associated with the drug.
Eli Lilly’s anti-amyloid drug donanemab also made a huge hubbub. Researchers presented positive results from Phase 2 and Phase 3 clinical trials and submitted data to the FDA, which will decide whether to approve the drug later this year.
However, many other biotechnology and drug companies have also made significant announcements and progressed in developing other kinds of drugs to treat Alzheimer’s. Here are the updates you might have missed.
More drugs targeting amyloid
Companies are developing drugs in the form of vaccines, pills, and antibodies which target beta-amyloid plaques in some way to treat mild cognitive impairment and early-stage Alzheimer’s.
Vaccines
Several companies are developing vaccines that train the body’s immune system to fight off beta-amyloid. AC Immune and Vaxxinity have both received FDA fast-track designations for their vaccines, which will speed up the review of these drugs in the future.
- AC Immune’s ACI-24.060: In a Phase 1b/2 trial, the drug was shown to be a safe way to activate the immune system.
- Araclon Biotech’s ABvac40: In a Phase 2 trial, the drug produced an immune response in participants but did not affect cognition.
- Vaxxinity’s UB-311: Vaxxinity published the results from its Phase 2 trial, finding that the drug was safe and induced an immune response. The trial did not find that the drug significantly slowed cognitive decline. The company is looking for a Phase 3 clinical trial partner.
Small-molecule drugs
Other companies are developing small-molecule drugs, pills or capsules that don’t require intravenous infusion.
- Alzheon’s ALZ-801: This drug prevents healthy forms of beta-amyloid from turning toxic and sticking together. Its Phase 2 study suggests that the drug may slow the progression of Alzheimer’s and, importantly, is safe for people carrying the APOE4 Alzheimer’s gene who are otherwise at risk of brain bleeds from anti-amyloid drugs like Leqembi. The drug is currently being tested in Phase 3 trials.
- Cognition Therapeutics’ Elayta: The company announced that they are recruiting participants for a Phase 2 trial of its Elayta, which prevents beta-amyloid proteins from sticking to brain cells.
More antibodies
True Binding developed an antibody-based drug that prevents beta-amyloid from aggregating by targeting the protein that allows beta-amyloid plaques to stick together. It presented some Phase 2 data suggesting that the drug may slow cognitive decline.
Dementia Biomarkers 101: What Does Beta-Amyloid Do In the Brain?
Teeing up tau as the next target
Several companies target tau protein tangles in the brain — which are considered major drivers of cognitive decline.
Most of these drugs are aimed at treating mild cognitive impairment and the early stages of Alzheimer’s.
- Johnson & Johnson/AC Immune’s ACI-35.030: This vaccine teaches the body’s immune system how to fight off tau proteins. The company announced that they will test their drug in a Phase 2 trial of 500 participants who have tau and are at risk of developing Alzheimer’s.
- Axon Neurosciences AADvac1: The company presented Phase 2 data for its AADvac1 tau vaccine. The vaccine may have slowed cognitive decline in one subset of patients.
- Biogen’s BIIB080: This drug is one of the first gene therapies in development for Alzheimer’s disease. It works by “silencing” the tau gene so that tau tangles do not form. Biogen will be moving this drug to Phase 2 trials.
- Bristol Meyer Squibb/Prothena’s PRX005: The drug is a monoclonal antibody designed to target tau proteins in the brain. It attaches to tau and tells the immune system to destroy the pathological protein. Data presented in 2023 by Prothena suggests that the drug is safe.
- Oligomerix’s OLX-07010: Oligomerix began testing its small-molecule drug OLX-07010, which prevents tau proteins from sticking together, in Phase 1 trials this year.
Drugs targeting inflammation and cell death
Many other drugs, in one way or another, target the brain to modify the immune system, reduce inflammation and protect brain cells from dying.
- Anavex Life Sciences’ blarcamesine: The company presented data from the Phase 2b/Phase 3 trial of its neuroprotective drug, showing it may slow cognitive decline by over 48 weeks.
- BioVie Pharma’s NE3107: The company announced its drug failed the Phase 3 trial of its immune-modulating drug. The company wrote in its press release that the failure occurred partly because 15 of its 39 clinical trial sites did not follow study protocol and violated good clinical practice.
- Cassava Sciences’ simufilam: The company presented more data from its Phase 2 trial of simufilam. This was overshadowed by allegations of misconduct and an investigation of one of the lead researchers behind the drug. A Phase 3 trial is ongoing.
- COYA Therapeutics’ COYA 301: The company’s injectable drug, which stimulates T-regulatory immune cells, was found safe and potentially promising in a cohort of 8 patients in various stages of Alzheimer’s disease.
- Longeveron’s lomcel-B: In Phase 2 trials of the drug, made out of bone marrow stem cells, researchers found it was safe and could slow cognitive decline.
- Synaptogenix’s bryostatin-1: The company presented Phase 2 data of the company’s immune-modulating drug in patients with moderate and severe Alzheimer’s. The data suggests the drug might only slow decline in severe patients.
- T3D Therapeutics’ TD-359: The drug acts like “insulin for the brain” and helps prevent brain cells from starving. Its Phase 2 trial in patients with mild Alzheimer’s disease was not positive. The researchers found one subgroup, defined after the trial, did appear to benefit.
- Cognito Therapeutics: The company developed a wearable device that uses specific sounds and wavelengths of light to stimulate a specific form of brain activity called gamma oscillations. Its Phase 2 trial suggests that the device may slow cognitive decline and prevent brain shrinkage in patients with mild to moderate Alzheimer’s.
