Upcoming Alzheimer's Treatments: 5 Key Data Releases in 2024

The quest for effective Alzheimer's treatments has been a long and challenging journey, marked by numerous setbacks. However, recent developments suggest that the horizon is brightening with the potential of two groundbreaking therapies. Biogen and Eisai's Leqembi received full regulatory approval last July, and Eli Lilly's donanemab might soon follow suit, with a decision anticipated before the year's end.

The journey in the anti-amyloid domain has been tumultuous, especially after the contentious approval of Aduhelm in 2021. Despite this, Biogen has ceased sales of this therapy and halted the post-approval study. Yet, this has not deterred other companies from advancing their experimental drugs.

Graig Suvannavejh, a senior analyst in biopharmaceuticals and biotechnology equity research at Mizuho Americas, remarks that the field of Alzheimer's treatment is still in its infancy. Many of the drugs under development are targeting specific aspects of the disease, such as TREM2 and the hepatocyte growth factor (HGF) system. Suvannavejh envisions a future where a combination therapy, akin to those used in cancer treatments, will become the norm.

Here are five promising Alzheimer's drugs with anticipated data releases in 2024 that have captured Suvannavejh's interest:

Alector/AbbVie's AL002: This monoclonal antibody developed by Alector Therapeutics is aimed at TREM2, a receptor whose dysfunction is linked to Alzheimer's and other dementias. AL002 is designed to activate TREM2 signaling to enhance cell survival and function. Currently in Phase II trials, the data from the fourth quarter of 2024 will be crucial for the program's continuation, with AbbVie holding opt-in rights for Phase III development if the results are promising.

Athira Pharma's fosgonimeton: This novel therapy is intended to regulate the HGF system, activating neuroprotective and anti-inflammatory pathways. Despite an initial setback in a Phase II trial for Parkinson's disease dementia, a significant cognitive improvement was observed when the study population was narrowed. Athira has completed enrollment for a Phase II/III trial for mild-to-moderate Alzheimer's, with results expected later this year. Suvannavejh finds fosgonimeton intriguing, highlighting the unique drug target HGF.

Alzheon's ALZ-801: This oral treatment from Alzheon could be the first to modify the disease's course by preventing the formation of amyloid oligomers, the precursors to amyloid plaques. ALZ-801 is being tested on patients with the APOE4 gene variant, who are more prone to amyloid-beta accumulation. Phase II trial results indicated that ALZ-801 preserved the hippocampus without increasing the risk of ARIA, a side effect associated with anti-amyloid therapies. ALZ-801 is now in Phase III trials, with results expected mid-year.

Prothena's PRX012: With the FDA's Fast Track designation, Prothena's anti-amyloid antibody has the potential to be a best-in-class drug. PRX012 is administered subcutaneously, offering a more convenient alternative to intravenous treatments. Despite being in Phase I, investor interest was evident last year, driven by the drug's formulation, efficacy, and potential to avoid ARIA. However, clinical readouts have been delayed.

Axsome Therapeutics' AXS-05: Unlike the other treatments, AXS-05 is a symptomatic therapy, not a disease-modifying one. Axsome is testing a repurposed antidepressant for Alzheimer's-related agitation, a common issue affecting about 70% of Alzheimer's patients. With positive Phase II and III data, Axsome's pivotal Phase III study results are expected in the second quarter of 2024. Suvannavejh notes that if successful, AXS-05 would be the only treatment for Alzheimer's agitation without a black box warning for elderly patients with dementia-related psychosis.

As of January 2023, there were numerous trials underway for Alzheimer's disease, with many more expected in 2024. Suvannavejh expresses excitement for the innovation in Alzheimer's disease treatment, indicating a promising future for patients.