July 23, 2024

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5 Alzheimer’s Disease Clinical Trials to Watch in 2024

5 Alzheimer’s Disease Clinical Trials to Watch in 2024



5 Alzheimer’s Disease Clinical Trials to Watch in 2024

Alzheimer’s Disease (AD) is one of the primary types of dementia, affecting millions worldwide. This disease deprives patients of their memory and autonomy, significantly impacting their lives.

It has spurred global efforts from scientists and researchers to relentlessly seek and develop new treatment methods aimed at slowing down or reversing its adverse effects.

In recent years, there have been significant breakthroughs in AD treatment. The US FDA has approved two monoclonal antibodies targeting beta-amyloid protein for market release.

Among them, lecanemab received full FDA approval in July last year. Donanemab by Eli Lilly and Company is currently under FDA review, with results expected to be announced early this year.

In addition to the aforementioned AD therapies, more are in the pipeline. A recent article published by industry media BioSpace noted that as of January 2023, a total of 187 clinical trials were evaluating 141 drugs for treating Alzheimer’s disease, offering hope for more treatment options for AD patients.

The article highlighted five clinical trials expected to yield positive data in 2024 and worthy of attention. In this piece, we’ll share insights on each, drawing from publicly available information.

5 Alzheimer's Disease Clinical Trials to Watch in 2024


Drug Name: AL002

  • Developing Companies: Alector Therapeutics, AbbVie
  • Therapy Type: Monoclonal Antibody
  • Target: TREM2
  • Trial Phase: Phase 2 Clinical Trial

AL002, developed by Alector Therapeutics, is a humanized monoclonal antibody targeting Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), a significant genetic risk factor for sporadic AD. TREM2, a transmembrane receptor, is expressed on some innate immune cells and selectively on microglia, constituting the brain’s immune system. Reduced TREM2 function may lead to Alzheimer’s disease and other forms of dementia. AL002 works by activating the TREM2 signal to improve cell survival and proliferation and increase microglial activity, counteracting this functional decline. The clinical benefits of this activity are yet to be fully understood and are the focus of AL002 clinical trials.

In October 2017, Alector Therapeutics entered an agreement with AbbVie to jointly develop AL002. Currently, AL002 is undergoing testing in a Phase 2 clinical trial. Alector Therapeutics plans to announce the safety and efficacy data of AL002 in the fourth quarter of 2024, which will determine the future of the project. If the results are compelling enough, AbbVie will choose to advance AL002 into Phase 3 clinical trials.

Drug Name: Fosgonimeton

  • Developing Company: Athira Pharma
  • Therapy Type: Small Molecule Drug
  • Target: HGF
  • Trial Phase: Phase 2/3 Clinical Trial

Fosgonimeton, developed by Athira Pharma, is a potential first-in-class small molecule drug that enhances the activity of the HGF/MET signaling pathway. This pathway mediates natural repair mechanisms in the healthy nervous system. By targeting the neural pathway repair mechanism, fosgonimeton has the potential to improve neuronal function and change the course of the disease. Furthermore, fosgonimeton is expected to be used in combination with anti-amyloid or anti-tau therapies.

Currently, fosgonimeton is being tested in a Phase 2/3 clinical trial for its efficacy in treating patients with mild to moderate Alzheimer’s disease. The trial has completed patient enrollment and is expected to obtain topline results in the second half of 2024. Previously, encouraging results were obtained from Phase 2 clinical trials of fosgonimeton for the treatment of dementia associated with Parkinson’s disease and Lewy body dementia, supporting the modulation of the neurotrophic HGF system as a potential therapeutic approach for neurodegenerative diseases.

Drug Name: ALZ-801

  • Developing Company: Alzheon
  • Therapy Type: Small Molecule Drug
  • Target: Beta-amyloid Protein
  • Trial Phase: Phase 3 Clinical Trial

ALZ-801, a oral small molecule drug developed by Alzheon, is a precursor drug to tramiprosate. ALZ-801 at Phase 3 clinical doses can inhibit the formation of neurotoxic beta-amyloid oligomers, potentially altering the course of Alzheimer’s disease. The therapy was granted Fast Track designation by the FDA in 2017.

Previously released Phase 2 clinical data showed that at 52 weeks, ALZ-801 caused a significant 41% decrease in plasma P-tau181 protein compared to baseline (p=0.032). Neuroimaging analysis also showed preserved hippocampal volume in patients compared to the control group, indicating the drug’s potential neuroprotective effect on brain structure. Additionally, at months 3, 6, and 12, patients’ memory test scores were higher than baseline, consistent with observed biomarker levels and brain impact results. ALZ-801 demonstrated good safety in over 2000 Alzheimer’s disease patients, consistent with previous trial results, with no observed cases of vasogenic brain edema (a side effect sometimes seen with other anti-amyloid therapies). The drug is currently undergoing testing in Phase 3 clinical studies, with data expected in the mid-year.

Drug Name: PRX012

  • Developing Company: Prothena
  • Therapy Type: Monoclonal Antibody
  • Target: Beta-amyloid Protein
  • Trial Phase: Phase 1 Clinical Trial

PRX012 is a subcutaneously injected next-generation high-affinity anti-beta-amyloid antibody with the potential to become a best-in-class therapy. Due to its subcutaneous administration, it offers advantages over intravenous therapy, including ease of use and absence of amyloid-related imaging abnormalities (ARIA). Previously, the FDA granted PRX012 Fast Track designation for the treatment of AD.

In preclinical experiments, PRX012 has shown clearance of amyloid deposits mediated by microglia in brain tissue. Currently, PRX012’s Phase 1 clinical trial is progressing as planned, with updates expected later this year.

Drug Name: AXS-05

  • Developing Company: Axsome Therapeutics
  • Therapy Type: Small Molecule Drug
  • Target: N-Methyl-D-Aspartate (NMDA) Receptor
  • Trial Phase: Phase 3 Clinical Trial

AXS-05, developed by Axsome Therapeutics, is a novel oral NMDA receptor antagonist with multiple mechanisms of action intended for the treatment of major depressive disorder (MDD) and other central nervous system diseases. AXS-05 contains two active ingredients: dextromethorphan and bupropion. Dextromethorphan is a non-competitive NMDA receptor antagonist, while bupropion is used to enhance the bioavailability of dextromethorphan and is also a norepinephrine and dopamine reuptake inhibitor.

In August 2022, AXS-05 was approved by the FDA for the treatment of MDD in adult patients, becoming the “first” oral therapy for depression with a new mechanism of action in over 60 years. In addition to MDD, AXS-05 is currently being developed for the treatment of agitation symptoms in AD. According to data from Axsome Therapeutics, approximately 70% of AD patients experience agitation symptoms, which are associated with functional decline and increased mortality in AD patients. Previously, AXS-05 had received breakthrough therapy designation from the FDA for the treatment of MDD and agitation symptoms in Alzheimer’s disease.

Currently, research on AXS-05 for the treatment of agitation symptoms in AD has progressed to Phase 3 clinical trials. Previously released trial results showed that compared to placebo, AXS-05 reduced the risk of agitation symptom recurrence in Alzheimer’s disease patients by 3.6 times (HR: 0.275, p=0.014), while significantly reducing the recurrence rate of agitation symptoms in patients. The company is expected to announce data from the second pivotal Phase 3 clinical trial in the second quarter of this year. There is currently no therapy available for agitation symptoms in elderly AD patients with dementia-related psychiatric illnesses, and if approved, AXS-05 could fill this gap.

In addition to these 5 studies, we look forward to more therapies announcing positive clinical trial data to benefit AD patients as soon as possible!

5 Alzheimer’s Disease Clinical Trials to Watch in 2024

References:

[1] 5 Alzheimer’s Data Readouts to Watch in 2024. Retrieved February 6, 2024, from https://www.biospace.com/article/five-alzheimer-s-data-readouts-to-watch-for-in-2024/

[2] Alector Announces Completion of Enrollment in the INVOKE-2 Phase 2 Clinical Trial of AL002, a TREM2 Monoclonal Antibody, in Individuals With Early Alzheimer’s Disease. Retrieved February 6, 2024, from https://investors.alector.com/news-releases/news-release-details/alector-announces-completion-enrollment-invoke-2-phase-2

[3] Athira Pharma Completes Enrollment of Phase 2/3 LIFT-AD Clinical Trial of Fosgonimeton in Mild-to-Moderate Alzheimer’s Disease. Retrieved February 6, 2024, from https://investors.athira.com/news-releases/news-release-details/athira-pharma-completes-enrollment-phase-23-lift-ad-clinical

[4] ALZ-801 (valiltramiprosate) potentially the first oral disease-modifying treatment for Alzheimer’s disease. Retrieved February 6, 2024, from https://alzheon.com/pipeline/alzheon-alz-801/

[5] Prothena Provides Updates on PRX012, PRX123, Birtamimab and Portfolio Programs. Retrieved February 6, 2024, from https://www.businesswire.com/news/home/20240108622841/en

[6] what is alzheimer’s disease agitation? Retrieved February 6, 2024, from https://www.axsome.com/conditions/alzheimers-disease-agitation

(source:internet, reference only)


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