The anti-amyloid drug Leqembi and diabetes drug liraglutide take center stage at AAIC 2024.
During the Alzheimer’s Association International Conference in Philadelphia last week, researchers and drug companies presented data on a range of different Alzheimer’s drugs. Amidst all the jargon and data visualizations were some disappointments, some wins, and some generally interesting findings for the future of Alzheimer’s treatment. Here are the highlights:
- Ongoing studies have found that Leqembi should be taken long-term. After 18 months, patients may go down from biweekly to monthly infusions of the drug without additional risk of side effects.
- The diabetes drug liraglutide, similar to Wegovy, appears to ease the cognitive symptoms of Alzheimer’s and slow brain shrinkage.
Disease-modifying small molecule drugs
Anavex Life Sciences’ Blarcamesine: Blarcamesine is an experimental Alzheimer’s pill that activates a protein called the sigma-1 receptor in brain cells, turning on the cells’ maintenance and cleaning pathway. This process, called autophagy, helps brain cells get rid of brain build-ups of amyloid, tau, and other junk. The Phase 2/3 trial, which took place over 11 months, suggests the drug might slow cognitive decline and brain shrinkage. This data was initially shared a few years ago, but the company had to redo their statistical analysis to be more in line with U.S. regulators. Anavex plans to file for approval in Europe this year and is in conversation with the FDA but has not shared a timeline for filing for U.S. approval.
Biomed Industries’ NA-831: NA-831 is a pill that helps brain cells regrow and protect themselves from damage. In a Phase 2 trial, the drug appeared to boost cognition in patients with mild cognitive impairment, as well as mild and moderate Alzheimer’s, rather than just slowing the course of cognitive decline.
Liraglutide: Liraglutide is a GLP-1 agonist, like Wegovy or Ozempic, that’s approved for treating diabetes and obesity in the U.S. It works by mimicking the GLP-1 hormone which affects the brain’s metabolism. In a Phase 2 trial in Alzheimer’s patients, the drug slowed cognitive decline and brain shrinkage over the course of a year.
T3D Therapeutics’ T3D-959: In Alzheimer’s disease, brain cells start to starve themselves. T3D-959 is designed to treat the disease by helping the brain feed itself again. In a Phase 2 trial of mild-to-moderate Alzheimer’s, participants who received the drug daily for 24 weeks did not appear to slow cognitive decline, but it did appear to lower the levels of amyloid and tau. The company intends to move forward with a Phase 3 trial of the drug in the near future.
Disease-modifying biologics: Antibodies, vaccines, cell infusions and more
Biogen’s BIIB080: BIIB080 is a gene-silencing therapy that reduces tau build-up in the brain by blocking signals and lessening production of the protein. In the Phase 1b trial, the drug reduced the levels of tau protein. It may slow cognitive decline, but future trials are needed. BIIB080 is currently in a Phase 2 trial with results expected by 2027.
Eisai and Biogen’s Leqembi: An analysis suggests that brain shrinkage caused by Leqembi isn’t associated with worse cognitive outcomes in the short term. In addition, researchers provided evidence suggesting that patients should continue to work with their doctor to stay on Leqembi for the long term with a reduction in infusion frequency after 18 months.
Longeveron’s Lomecel-B: This drug is made from mesenchymal stem cells taken from a patient’s bone marrow. A Phase 2a trial showed that the treatment may reduce brain shrinkage and slow cognitive decline. Since the study was small and only lasted 39 weeks, the company’s presenter noted that a longer trial with more participants is needed to know for certain. The company has received fast-track designation in the U.S. which speeds up the process of reviewing the company’s drug applications in the future. Longeveron has not yet registered any additional Phase 2 trials for Alzheimer’s.
NKGen Biotech’s SNK01: SNK01 is an experimental Alzheimer’s treatment made out of a powerful type of immune cell, called Natural Killer cells. In a small study of 10 patients, the treatment slowed or stabilized cognitive decline, and reduced the levels of biomarkers associated with cognitive impairment in most participants. The company received FDA clearance this year to run a Phase 2 trial in the U.S.
Drugs for psychiatric symptoms
As many as half of people who develop Alzheimer’s dementia experience agitation. Others develop anxiety or depression. Some drugmakers are working on treatments to ease or alleviate these behavioral symptoms for patients in the later stages of the disease.
Axsome Therapeutics’ AXS-05: This drug is a combination of two antidepressant medications, already approved for treatment of depression in the U.S. Researchers presented data from a Phase 3 trial that tested the drug in people with Alzheimer’s who had symptoms of agitation. Patients who took the drug were about three times less likely to experience a relapse in agitation symptoms than patients who received the placebo.
Escitalopram: Escitalopram is an antidepressant drug approved in many countries for treating the symptoms of anxiety and depression. Researchers presented data that suggested the drug was not effective at treating agitation in people with Alzheimer’s.
