Recent developments in Alzheimer's drug research are increasingly focusing on expanding treatment targets to include tau protein and combination therapies. While anti-amyloid treatments have been shown to slow disease progression, they have not completely halted the disease, leading to a growing analysis of complementary treatment options.
According to industry reports, the abnormal accumulation of amyloid beta is considered one of the key pathologies of Alzheimer's disease. In South Korea, a monoclonal antibody treatment targeting amyloid protein is set to be introduced in 2024, marking the beginning of targeted therapies.
In the disease progression process, amyloid is identified as a relatively early pathology, while tau is recognized as a later pathology closely associated with neuronal damage and clinical symptoms. Recent advancements in tau positron emission tomography (PET) and fluid biomarker technologies have improved patient screening and treatment efficacy evaluation, providing a foundation for a combination approach targeting tau.
According to statistics from the Alzheimer's Association, a total of 158 Alzheimer's treatments are expected to be developed this year, with 192 clinical trials evaluating these treatments as of January.
Internationally, Biogen's tau generation inhibitor candidate, diranersen, has garnered attention. Although the primary endpoint was not met in the recently announced Phase 2 CELIA study, it demonstrated a reduction in total tau levels in cerebrospinal fluid by an average of 50-65%, and some cognitive improvement was observed in the low-dose group, indicating the potential for tau-targeted therapies.
Development strategies have diversified to include methods that inhibit the propagation of pathological tau, as well as antisense oligonucleotides (ASO) and small interfering RNA (siRNA). However, no tau-targeted therapies have been approved to date, and there is still insufficient evidence to prove their efficacy and safety compared to anti-amyloid treatments.
Professor Kang Dong-woo of the Department of Psychiatry at Seoul St. Mary's Hospital stated, "The fact that tau is located inside neurons, the heterogeneity of pathological tau forms, brain delivery, and the appropriate timing for treatment are still challenges that need to be addressed. Ultimately, it is likely that these therapies will develop into complementary treatments used in combination or sequentially rather than replacing amyloid treatments."
In South Korea, related drug development is also ongoing. Notable candidates include ADEL-Y01, co-developed by Oscotec and ADEL, and DA-7503 from Dong-A ST.
ADEL-Y01 is an antibody that selectively targets pathological acetylated tau, with initial safety and pharmacokinetic data secured, and it was licensed to Sanofi last year. However, its efficacy in existing patients has yet to be confirmed. DA-7503 has also completed Phase 1 clinical trials in healthy individuals, with efficacy validation still pending.
Professor Kang noted, "The domestic achievements are at an early stage, confirming the potential for clinical entry and global commercialization. It is crucial to demonstrate in future Phase 2 trials whether changes in tau PET and cerebrospinal fluid markers translate into delays in cognitive decline and daily functioning in patients."
* This article has been translated by AI.
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