Advancements in Alzheimer’s Disease Drug Innovation and Funding Programs in 2024

Alzheimer’s disease (AD) is a progressive neurodegenerative brain condition resulting in cognitive decline and dementia. Despite some patients surviving up to 20 years post-diagnosis, they typically experience severe disability and require caregiver assistance. Currently, over a hundred therapeutic drugs are undergoing clinical trials aimed at slowing disease progression. 

Advancing Anti-Aβ Therapies in Alzheimer’s Disease

AD’s physiological mechanisms include abnormal β-amyloid protein (Aβ) deposition, tau protein phosphorylation, reduced acetylcholine activity, glutamate toxicity, autophagy, inflammatory responses, and mitochondrial dysfunction.  Current and future therapies will prioritize developing anti-Aβ and anti-tau proteins, targeting mitochondria, and creating multi-target drugs.

In 2023, the U.S. Food and Drug Administration (FDA) approved the anti-Aβ drug LEQEMBI (lecanemab-irmb), jointly developed by Eisai and Biogen, using the accelerated approval pathway. Patients in early-stage Alzheimer’s with mild cognitive impairment or mild dementia showed reduced Aβ plaque deposits in the brain after 18 months of treatment.

Moving into 2024, Eisai expanded their FDA approval for monthly intravenous maintenance doses through a supplemental biologics license application (sBLA). Additionally, Eisai attained FDA Fast Track Designation (FTD) in May 2024, initiating submissions for weekly maintenance doses of LEQEMBI in a subcutaneous auto-injector format, expected to become a primary treatment method.

Most recently, the latest approval by the FDA of Eli Lilly and Company’s Kisunla (donanemab-azbt) has been well received. Here, a once-monthly intravenous injection for adults with early symptomatic AD, including mild cognitive impairment and mild dementia with confirmed amyloid pathology showcases a big step forward in the treatment of AD. This treatment is the first therapy targeting amyloid plaques, supported by studies demonstrating its potential to slow disease progression.

Advancements in Anti-Aβ Therapies Reveal Promising Candidates and Novel Mechanisms in AD Research

Within the landscape of anti-Aβ drugs, alongside LEQEMBI and Kisunla, other promising candidates are emerging. Hoth Therapeutics is advancing HT-ALZ, an orally soluble film formulation, providing patient convenience and certain distinct characteristics that set it apart from existing products.

Preclinical studies demonstrate that HT-ALZ significantly reduces Aβ plaque deposition in mice compared to placebo-treated animals and baseline Aβ levels. Targeting the P/Neurokinin 1 receptor pathway, HT-ALZ offers a novel approach to combating neuroinflammation and cognitive deficits associated with Alzheimer’s disease. By specifically antagonizing NK1 receptors, HT-ALZ not only lowers soluble Aβ levels in brain interstitial fluid but also markedly reduces anxiety behaviors in preclinical models while enhancing cognitive function.

In addition to these anti-Aβ therapies, several drugs with new mechanisms are actively under development. For instance, ALX-001, a first-in-class drug, is preparing to enter Phase II clinical trials. This small molecule oral therapy targets synapses, modifies disease progression, and effectively penetrates brain tissue. ALX-001 functions as a silent allosteric modulator, selectively blocking pathogenic receptor activation while preserving essential glutamate signaling for normal cognitive function.

Expert Consultation on AD Drug Development and Funding Programs

The Alzheimer’s Drug Discovery Foundation (ADDF) and Harrington Discovery Institute jointly established the ADDF-Harrington Scholar Award to foster and identify potential Alzheimer’s therapies advancing from academic research to clinical development. This initiative provides funding and drug development support aimed at treating or preventing Alzheimer’s disease, dementia, and age-related cognitive decline. It offers commercialization guidance, clinical development suggestions, intellectual property (IP) review, and project management support. By encouraging collaboration beyond traditional biotech or pharmaceutical company silos, this program aims to accelerate research and clinical applications in neurodegenerative diseases.

In 2024, significant strides in AD drug innovation and funding underscore a dynamic landscape poised for breakthroughs. Multiple therapeutic approaches, including anti-Aβ and anti-tau proteins targeting β-amyloid deposition, tau protein phosphorylation, and neuroinflammation, advance through clinical trials. FDA approvals of LEQEMBI and Kisunla mark pivotal milestones for reducing Aβ plaques in early-stage AD. Emerging therapies like HT-ALZ and ALX-001 introduce innovative mechanisms, potentially reshaping AD treatment. Collaborative efforts such as the ADDF-Harrington Scholar Award promote integrated research, aiming to mitigate cognitive decline and neuroinflammation while bolstering patient outcomes through diverse strategies and robust funding. These advancements promise to redefine neurodegenerative disease management, bringing renewed hope to patients and caregivers alike.

Original article authored by Ula Yang

Author

Bernice Lottering