[New Wave] On the Eve of the Era of Alzheimer's Treatment Opening

Biogen's Alzheimer's dementia treatment 'Aducanumab (brand name Aduhelm)' [Image source=AP Yonhap News]

Recently, the U.S. Food and Drug Administration (FDA) granted conditional approval for Aducanumab, an Alzheimer's treatment jointly developed by Biogen and Eisai. Until now, only four Alzheimer's drugs?Donepezil, Rivastigmine, Galantamine, and Memantine?had received FDA approval. This marks the first approval of an Alzheimer's treatment in 18 years since Memantine was last authorized in 2003.

The drugs approved so far have been used to improve symptoms rather than provide a fundamental cure for Alzheimer's. Various approaches based on mechanisms such as viruses, bacteria, and inflammation have been explored to address the root causes of Alzheimer's. Aducanumab is significant as a 'true therapeutic agent' that can effectively remove insoluble amyloid-beta proteins from brain tissue, thereby inhibiting disease progression or preventing onset.

The FDA approval process for Aducanumab resembled a rollercoaster. It attracted industry attention in 2016 when it was designated as a 'Fast Track' by the FDA, but after announcing the failure of Phase 3 clinical trials in 2019, the company reversed its statement following further analysis, claiming clinical success. Biogen applied for FDA approval based on clinical trials showing that patients receiving high doses experienced 22% less worsening of dementia symptoms on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale compared to placebo and low-dose groups.

At one point, 8 out of 11 FDA advisory committee members opposed recognizing efficacy, leading to predictions of failure. However, the FDA prioritized market supply through 'accelerated approval,' a process for drugs with high patient demand but no existing treatments, granting conditional approval on the premise of demonstrating clinical significance through post-marketing Phase 4 studies. Meanwhile, concerns were raised not only about efficacy but also about the high annual treatment cost of approximately 60 million KRW, which some considered excessive relative to its benefits.

Despite these controversies, Aducanumab is significant for presenting a turning point as a causal treatment for Alzheimer's, one of humanity's most burdensome diseases. Since 1998, over 120 global new drug development projects have targeted Alzheimer's, but only five drugs, including Aducanumab, have been approved.

With population aging, the number of Alzheimer's patients is rapidly increasing. This imposes unimaginable direct and indirect social costs not only in South Korea but also in many countries. The U.S. President's Council of Advisors on Science and Technology warned that without innovative Alzheimer's treatments, the U.S. could face annual social costs of 1,000 trillion KRW.

Domestic companies are also focusing on developing global new drugs targeting diseases with large 'unmet needs.' Since passing through the FDA gateway is essential for global drug recognition, the Aducanumab approval case should be re-recognized as a need to adopt approaches targeting rare and intractable diseases with significant unmet needs in new drug development strategies.

Given the efficacy controversies surrounding Aducanumab, multifaceted efforts to overcome these challenges will also be necessary. This could present opportunities for capable domestic Alzheimer's treatment developers to conduct research that effectively removes amyloid by crossing the vascular-brain barrier or to propose collaborative clinical studies that enhance therapeutic efficacy through combination therapies with existing drug candidates.

Jung Yuntaek, Director of the Pharmaceutical Industry Strategy Research Institute