[100-Year Brain Health③] Fierce Competition in Developing Treatments for Alzheimer's of Unknown Cause

First-ever FDA Conditional Approval of 'Aduhelm'
EMA Rejects Approval... Insufficient Conclusion in Korea Too
Clinical Improvement Difficult to Confirm, Side Effects Also a Concern

Unclear Pathogenesis Causes Diverse Research Directions
Active Development Attempts Underway Domestically

Biogen-Eisai's Alzheimer's treatment 'Aduhelm (generic name Aducanumab)'

[Asia Economy Reporter Chunhee Lee] The U.S. Food and Drug Administration (FDA) granted the first-ever approval of Aduhelm (generic name aducanumab) as a treatment for Alzheimer's dementia, but the dream of conquering Alzheimer's, which had shown hope, has once again been dashed. However, with the approval of a treatment drug, the door to the Alzheimer's treatment market has opened wide, and competition to develop follow-up treatments is heating up.

‘First Treatment’ Raised Expectations but

Aduhelm, an Alzheimer's treatment jointly developed by Biogen and Eisai, received the world's first conditional approval from the FDA for a dementia treatment in June last year. However, in December, the European Medicines Agency (EMA) rejected its approval, citing difficulties in confirming clinical improvement and concerns about side effects. In Korea, the Central Pharmaceutical Affairs Deliberation Committee concluded last month that the Phase 3 clinical trial was "insufficient to be considered confirmatory clinical evidence." One committee member who attended stated, "While a reduction in amyloid beta (Aβ) was confirmed during use, the results were so minimal that the drug was judged ineffective for dementia treatment."

This controversy is also attributed to the fact that the cause of Alzheimer's dementia has not been clearly identified. The primary suspected causes of Alzheimer's have long been Aβ and tau proteins. The theory is that removing the increase of Aβ protein plaques or the misfolding and tangling of tau proteins in the brain could enable dementia treatment. However, various hypotheses such as neuronal cell death and neuroinflammation have been proposed, and as Aduhelm, which targets Aβ, has faced setbacks, demand for other mechanisms is gradually increasing.

Unclear Pathogenesis... Diverse Development Directions

Globally, as of January, 172 clinical trials are underway targeting 143 candidate substances. Disease-modifying therapy (DMT) candidates number 119, with various targets including 20 for Aβ, 13 for tau, 23 for anti-inflammatory agents, and 19 for synaptic plasticity and neuroprotective agents.

Biogen and Eisai, who developed Aduhelm, are once again leading the way. In May, Biogen applied to the FDA for approval of ‘lecanemab,’ a follow-up drug with an Aβ mechanism. However, the Phase 3 clinical trial has not been fully completed, and the final clinical results are expected this fall. Other Aβ-targeting treatments such as Eli Lilly’s ‘donanemab’ and Roche’s ‘gantenerumab’ are also competing to complete Phase 3 trials within the year.

In Korea, various companies including GemVax, Aribio, GNT Pharma, and Mediphron have embarked on developing dementia treatments. Most pursue mechanisms that remove neuroinflammation or involve complex mechanisms rather than targeting Aβ or tau. GemVax is advancing Phase 3 trials domestically and Phase 2 trials in the U.S. for ‘GV1001.’ It targets a mechanism that views Aβ and tau as symptoms and aims to remove the fundamental cause?neuroinflammation?by inducing antioxidant and anti-aging effects in brain nerve cells.

Aribio, which completed Phase 2 U.S. trials last year for the oral drug ‘AR1001,’ plans to enter Phase 3 trials in the U.S. soon. Its multi-action mechanism includes dilating cerebral blood vessels to improve blood flow, inhibiting neuronal cell death, and activating proteins involved in long-term memory formation and brain cell proliferation.

GNT Pharma’s ‘crisdesalazine’ has completed Phase 1b dosing. This ingredient is commercialized as ‘Zedacure’ for canine cognitive dysfunction syndrome (CDS). GNT Pharma CEO Byungjoo Kwak explained, "When reactive oxygen species and inflammation occur, Aβ and tau increase and neuronal cells die," adding, "We will verify this mechanism in humans as well."