NeurologyLive® Year in Review 2023: Top Stories in Alzheimer Disease and Dementia

In 2023, the NeurologyLive^® staff was a busy bunch, covering clinical news and data readouts from around the world across a number of key neurology subspecialty areas. From major study publications and FDA decisions to societal conference sessions and expert interviews, the team spent all year bringing the latest information to the website's front page.

Among our key focus areas is Alzheimer disease and dementia, a field that experienced massive shifts in the therapeutic paradigm in the past 12 months, among other progress. Although major news items often appear among the top pieces our team produces, sometimes smaller stories reach those heights for other reasons—clinical impact and interest, or concerns about the small- or big-picture parts of care, for example. Whatever the reason for the attention these stories got, their place here helps provide an understanding of the themes in this field over the course of 2023.

Here, we'll highlight some of the most-read content on NeurologyLive^® this year. Click the buttons to read further into these stories.

1. CT1812’s Impact on Alzheimer-Related Biomarkers Suggests Altering Disease Effect

Announced results from a meta-analysis of a portion of the phase 2 SHINE study (NCT03507790) and the complete dataset from the phase 1b SPARC trial (NCT03493282) showed that CT1812, an oral sigma-2 (S2R) receptor modulator, had statistically significant impacts on Alzheimer disease-related biomarkers. Above all, the findings highlight a prominent role of CT1812 in regulating synaptic and amyloid-ß biology, the study investigators concluded.

2. New 12-Month Findings Highlight ALZ-801’s Clinical Effect on Alzheimer Biomarkers, Hippocampal Atrophy

In new 12-month data, ALZ-801 (Alzheon), an investigational oral amyloid oligomer inhibitor, continued to demonstrate its potential as a disease-modifying therapy for Alzheimer disease, represented by reductions in plasma phosphorylated-tau (p-tau)181, slowing of hippocampal atrophy, and stabilization of cognition. The final 24-month data will be released later this year.

3. FDA Approves Brexpiprazole as First Therapy for Alzheimer Agitation

The FDA approved an expanded indication for brexpiprazole (Rexulti; Otsuka/Lundbeck) to include the treatment of agitation associated with dementia becasue of Alzheimer disease. With the approval, it becomes the first marketed drug specific to treat Alzheimer disease agitation.

4. FDA Grants Traditional Approval to Lecanemab as Therapy for Early-Stage Alzheimer Disease

According to an announcement, the FDA granted traditional approval to Eisai’s Alzheimer disease medication lecanemab (Leqembi), a major step in enabling broader access and coverage of the therapy to the aging population. It originally received FDA approval under the accelerated approval pathway in January.

5. Donanemab Demonstrates Slowing of Alzheimer Disease Progression in Phase 3 TRAILBLAZER-ALZ 2 Trial

At the 2023 Alzheimer’s Association International Conference (AAIC), held June 16-20, in Netherlands, Amsterdam, full data from the pivotal, phase 3 TRAILBLAZER-ALZ 2 trial (NCT04437511) highlighted donanemab’s (Eli Lilly) impact on disease progression in individuals with early symptomatic Alzheimer disease.

6. Multiple Frameworks Better Interpret Alzheimer Trial Results to Meaningful Benefits

In an analysis of published research, presented at the 2023 Alzheimer’s Association International Conference, July 16-20, in Amsterdam, the Netherlands, results show that multiple frameworks better represent and translate findings from clinical trials in Alzhiemer disease. This finding suggests that there should be more expanded data, analyses, and frameworks for effectively defining and translating clinically meaningful patient-centered benefit for providers and patients in the Alzheimer disease field.

7. Epigenetic Therapy Demonstrates Efficacy in APOE Reduction for Alzheimer Disease

A study using an epigenome therapy strategy, the candidate demonstrated efficacy in editing of apolipoprotein (APOE) and APOE e4 expressions in human induced pluripotent stem cells (hiPSC) -derived neurons and the human isogenic APOEe4 organoids, ultimately reducing the levels of APOE-mRNA and the protein in both models. These findings provided in vitro and in vivo proof-of-concept of the therapy’s efficacy and suggests the candidate's ability to fine-tune APOE expression is translational toward the development of a therapeutic approaches to prevent or delay late-onset Alzheimer disease.

8. CMS Expands Coverage of PET Imaging for Confirmation of Alzheimer Diagnosis

After proposing coverage determination earlier in the summer, the Centers for Medicare and Medicaid Services (CMS) announced they will cover PET imaging for the diagnosis of Alzheimer disease, a major step toward ensuring access to novel treatments for patients who may be eligible.

9. Alzheimer Agent Simufilam Not Associated With ARIA-E, Phase 3 Reports Show

Interim data from REFOCUS-ALZ, a global phase 3 study NCT05026177), showed that treatment with simufilam (Cassava Sciences), an investigational agent in development for Alzheimer disease, was not associated with amyloid-related imaging abnormality (ARIA)-edema emergence. Final MRI data is expected at the conclusion of the study.

10. Phase 3 Findings Demonstrate Impacts of NE3017 in Alzheimer Cognition, Function

Announced topline data from a phase 3 study (NCT04669028) of BioVie’s Alzheimer agent NE3107 showed beneficial treatment effects over placebo that were potentially equal to or greater than data reported from previously approved antiamyloid therapies. In addition, patients on the permeable anti-inflammatory insulin sensitizer saw an average of more than 5 years of age deceleration in comparison with placebo, becoming the first such agent to demonstrate this impact on DNA methylation, according to the company.