Research Highlights from Padmaja Genesh August 2021

Published: Aug 13, 2021

FDA Limits Aduhelm’s Use to People With Mild Disease

The U.S. Food and Drug Administration (FDA) has pulled back the controversial and sweeping approval recently given to Aduhelm (aducanumab), a drug used to slow the progression of Alzheimer’s disease. The FDA has since restricted the treatment therapy to only early-stage Alzheimer’s patients rather than all with this disease.

Aduhelm, jointly developed by Biogen and Eisai, was approved under the FDA’s accelerated approval pathway based on data from a Phase 3 clinical trial showing that the medication could reduce levels of beta-amyloid plaques — the protein clumps in the brain that are characteristic of Alzheimer’s, in persons with mild cognitive impairment due to Alzheimer’s disease.

The FDA’s original June 2021 approval indicated simply that Aduhelm could be used for the treatment of Alzheimer’s disease. The new label reads,  “Treatment with Aduhelm should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials”.

Its development has been tumultuous, and its approval contentious. The controversy is continuing, even with Aduhelm’s more restrictive new label. The updated label was welcomed by the Alzheimer’s Association, a patient advocacy organization that had pushed for the FDA to approve Aduhelm.



Phase 3 Trial of Lecanemab Seeks People at Risk of Alzheimer’s Disease

The University of Wisconsin School of Medicine and Public Health is recruiting participants for a Phase 3 trial that will test the efficacy and safety of Lecanemab (BAN2401) in those who are at risk of developing symptoms of Alzheimer’s disease.

The global AHEAD (NCT04468659) study seeks to enroll 1,165 participants in North America to test Lecanemab in a larger group of people, after encouraging data in previous Phase 1 and 2 trials.

Developed by Eisai and Biogen, Lecanemab is an antibody designed to bind to a soluble, damaging version of the amyloid-beta protein that clumps into toxic plaques in the brain, contributing to Alzheimer’s. By binding to this form of amyloid-beta, the antibody is expected to “tag” it as harmful, promoting its clearance by the immune system before it clumps and forms toxic plaques. As such, it could potentially slow Alzheimer’s progression.

The AHEAD trial is the first of its kind to recruit people as young as 55 years who are at risk of developing Alzheimer’s as they age. The study will also test Lecanemab in patients from diverse communities that are typically underrepresented in clinical studies, specifically communities of color, which are known to have a higher incidence of Alzheimer’s.



Trial to Test Donanemab in People With Alzheimer’s Signs, Not Symptoms

A new Phase 3 trial, a collaboration between Eli Lilly and the Banner Alzheimer’s Institute, is planned to evaluate the potential of Donanemab in preventing  the cognitive and functional decline related to Alzheimer’s disease.

Called TRAILBLAZER-ALZ 3, the study will enroll people with brain changes of Alzheimer’s disease, but no clinical symptoms. Those with and without the ApoE4 gene variant, a known genetic risk factor for Alzheimer’s disease, are eligible to participate.

Donanemab, an antibody, is designed to recognize a harmful form of the beta-amyloid protein that clumps into toxic plaques in the brains of Alzheimer’s patients. By binding to this toxic form of beta-amyloid protein, Donanemab works to trigger an immune response that helps to clear these plaques, which might slow disease progression.

Data from the TRAILBLAZER-ALZ study, a Phase 2 trial (NCT03367403), showed that Donanemab was able to clear amyloid plaques from the brain, slow cognitive decline and the loss of daily life abilities when compared with a placebo.

Two other clinical trials — the long-term extension TRAILBLAZER-EXT (NCT04640077) study, and the global Phase 3 TRAILBLAZER-ALZ-2 (NCT04437511) study — are currently assessing the safety and efficacy of Donanemab in patients with early Alzheimer’s.



Alzheon Fully Enrolls Phase 2 Biomarkers Study of Oral ALZ-801

Patient enrollment is now complete for Alzheon’s Phase 2 clinical trial evaluating the effects of ALZ-801 on disease-related biomarkers in people with early Alzheimer’s, who have 2 copies of APOEE4 gene.

ALZ-801 is an oral  medication that prevents the formation and clustering of harmful proteins, such as beta amyloid and tau, that play a key role in Alzheimer’s disease. It has been given fast track status by the U.S. Food and Drug Administration (FDA) to support and speed its development.

While there is no single cause of Alzheimer’s, genetics is known to play a role in disease risk and progression. In particular, one APOE variant, known as the ε4 allele or APOE4, has been associated with an increased risk of Alzheimer’s, as well as with a higher risk of rapid disease progression. Estimates place around a quarter of all patients as having at least one copy of APOE4.

It is thought that people carrying two copies of APOE4 may benefit the most from an anti-amyloid therapy like ALZ-801.

Alzheon said it expects the first interim data from the study to be released in 2022.



New Study Will Test Cannabinoid-based Therapy for Agitation

SciSparc is set to start a Phase 2a study evaluating the safety and efficacy of SCI-110, its investigational cannabinoid-based therapy for Alzheimer’s disease and agitation and other behavioral disturbances.

People living with the disease often experience neuropsychiatric symptoms such as a lack of interest in activities (apathy), a lack of social relationships (social withdrawal), a lack of ability to sleep (insomnia), and a feeling of restlessness or worry (agitation).

While agitation occurs in about half of patients, there are, as of yet, no approved therapies for treating such symptoms in people with Alzheimer’s. SciSparc thinks a cannabinoid-based therapy could fill this unmet medical need.

SCI-110, formerly THX-110, combines two ingredients: dronabinol and palmitoyl ethanolamide. Dronabinol, a synthetic form of tetrahydrocannabinol (THC), the main active compound of cannabis, is approved by the U.S. Food and Drug Administration (FDA).

The second ingredient is CannAmide, the company’s oral tablet formulation of palmitoylethanolamide (PEA), a cannabinoid that is naturally produced by the body. It binds to the same receptors as compounds derived from cannabis.

SCI-110 is designed to inhibit the degradation of naturally produced cannabinoids while favoring the uptake of available dronabinol. The results of preclinical studies have shown that the SCI-110 combination is more efficient than dronabinol alone, thus enabling a lower dosage, causing fewer side effects.



Alzamend Seeks to Test AL001 as Dementia Therapy

Alzamend Neuro has requested approval from the U.S. Food and Drug Administration (FDA) to begin clinical trials to test AL001, its investigational lithium-based ionic cocrystal oral therapy for dementia related to Alzheimer’s disease.

The request was made in the form of an investigational new drug (IND) application that, if approved, will allow the start of Alzamend’s Phase 1 trial of AL001 evaluating AL001’s safety and appropriate dosing for future studies.

Using crystal engineering Alzamend has developed AL001, an ionic cocrystal of lithium. Ionic cocrystals are made up of an organic molecule and an inorganic salt, like lithium. This specific formulation of lithium is expected to be safer and therapeutically better than the existing lithium-based treatments.

Recent research has suggested that lithium can be beneficial for the treatment and prevention of Alzheimer’s. According to the company, findings from clinical studies suggested that lithium can preserve cognition and delay dementia, while reducing biomarkers linked with Alzheimer’s disease.

Alzamend also plans to develop its therapeutic vaccine, AL002, for the treatment of Alzheimer’s. The therapy is designed to stimulate the immune system and prevent harmful beta-amyloid buildup in the brains of people with Alzheimer’s. AL002 is currently in pre-clinical development.



New Mutations in Six Genes Found to Increase Alzheimer’s Risk

Researchers have identified new mutations in six genes that may increase the risk of developing Alzheimer’s disease.

Their study involved the genetic analysis of 19 families in Utah with higher-than-normal occurrence of the disease. The scientists found relevant mutations in the genes PELI3FCHO1, SNAP91COX6A2MUC16, and PIDD1.

The analysis also identified rare mutations in three other genes previously associated with increased Alzheimer’s risk — ABCA7, TTR, and NOTCH3.

These findings may help pinpoint new potential targets and therapeutic approaches for Alzheimer’s, according to Justin Miller, PhD, the study’s co-first author, and assistant professor at the University of Kentucky College of Medicine.


Compiled by Padmaja Genesh, Learning Specialist.