The Medical Frontline 'Dementia'... Can a Treatment Be Developed? [BioNOW]

Disease with Unclear Cause
'Aduhelm' Approved by FDA but Market Launch Blocked
Successful Further Development Could Enable 'Market Domination'

[Asia Economy Reporter Lee Chun-hee] Dementia affects one million people in South Korea alone, yet the cause of the disease remains unclear. If the cause is identified, it would explain why the pharmaceutical industry's competition to dominate the dementia treatment market is intensifying. Especially with Biogen-Eisai's 'Aduhelm' (generic name 'Aducanumab') becoming the first dementia treatment approved by the U.S. Food and Drug Administration (FDA), expectations for conquering dementia have grown even higher.

However, Aduhelm has yet to be properly launched in the market. Following the European Medicines Agency's (EMA) rejection of approval last December, the U.S. Medicare and Medicaid Services Center (CMS), which decides on insurance coverage, ruled that insurance would only apply to clinical trial participants, effectively deeming commercialization impossible. This decision was based on the fact that Aduhelm reduces 'amyloid beta protein,' which is likely the cause of dementia, but it has not been established whether this leads to clinical improvement in dementia symptoms, and the side effect known as 'ARIA' has also been problematic.

The biggest reason for Aduhelm's failure is that the cause of dementia has not yet been clearly identified. Until now, the most plausible cause of dementia was the amyloid beta hypothesis. It posits that amyloid beta protein in the patient's brain transforms into plaques and increases as symptoms worsen. However, with Aduhelm's setback, it has been confirmed that, besides amyloid beta, tau protein in the brain misfolds and tangles with each other, leading to attempts to develop various treatments targeting tau, synapses, immunity, and other mechanisms. Meanwhile, as aging increases, the estimated number of dementia patients aged 65 and older in South Korea alone is expected to reach 1.08 million by 2025 and 3.02 million by 2050, showing a steady rise in patient numbers.

A Larger Market Opens Instead

In particular, Aduhelm's failure is seen as an opportunity for other dementia treatment developers. Since there were no dementia treatments before, standards for approval were not properly established even if new drugs emerged, but with Aduhelm's appearance, a kind of 'standard' has been set. Moreover, since the effects shown by Aduhelm in clinical trials were not dramatic, if a drug can prove better efficacy in clinical trials, there is a possibility of gaining market dominance through FDA approval.

Overseas, competition to secure the second dementia treatment spot is intensifying. As of May last year, 152 clinical trials are underway worldwide for 126 candidate substances. Among these, 17 have entered Phase 3 clinical trials.

Among them, Biogen-Eisai is leading the competition again by applying for approval of a follow-up drug. Biogen recently submitted a Biologics License Application (BLA) for the follow-up drug 'Lecanemab' to the FDA and announced plans to continuously reduce Aduhelm's commercial infrastructure, effectively abandoning the Aduhelm business to focus on select priorities. Eli Lilly also revealed plans to soon apply for accelerated FDA approval of the Alzheimer's treatment 'Donanemab' and aims to complete FDA approval by next year.

In South Korea, various companies such as GemVax and Aribio are also rushing to develop dementia treatments. GemVax has completed the domestic Phase 3 and U.S. Phase 2 clinical trial plan approvals (IND) for 'GV1001' and is about to begin clinical trials soon. GV1001 targets the mechanism of removing neuroinflammation, the fundamental cause, by inducing antioxidant and anti-aging effects in brain nerve cells, viewing amyloid beta and tau proteins as symptoms. Aribio, which successfully completed the U.S. Phase 2 clinical trial of 'AR1001' last year, has announced plans to proceed with Phase 3 trials in the U.S. based on this.