[Science World] The Endless Battle in Developing New Drugs for Alzheimer’s Disease

Dementia completely destroys the lives of families. Moreover, there is currently no effective treatment for Alzheimer’s-type dementia. The cause of Alzheimer’s is the accumulation of a toxic substance called beta-amyloid (Aβ) in the brain, but the most commonly used drug, Aricept (generic name donepezil), is unrelated to beta-amyloid. Instead, it manages a neurotransmitter called acetylcholine to improve cognitive function. A complete cure is difficult to expect, and the progression of the disease cannot be fundamentally stopped.

However, since 2021, dementia drug development has entered a new phase. A drug called Aduhelm (generic name aducanumab), which prevents the accumulation of beta-amyloid, was introduced. It was jointly developed by the American company Biogen and the Japanese company Eisai. The U.S. Food and Drug Administration (FDA) conditionally approved this drug, stating, “Market it first while additionally verifying efficacy and safety.” However, the actual effect was not very good, and sales were sluggish. Eventually, clinical trials and sales of Aduhelm were completely halted at the end of January this year.

Although it failed, Aduhelm did open the door for new Alzheimer’s drug development. The Biogen-Eisai alliance developed a follow-up drug called Leqembi (generic name lecanemab), which also prevents the aggregation of beta-amyloid in the brain. It received formal approval last July and is performing well in the market. Sales in the first quarter of this year exceeded $19 million (about 26.2 billion KRW). This drug was also approved domestically on May 24. It is expected to be available for hospital prescriptions around the end of the year.

Another new drug has also emerged. The multinational pharmaceutical company Eli Lilly’s new drug, Kisunla (generic name donanemab), was approved by the FDA on the 2nd (local time). This drug not only prevents the aggregation of beta-amyloid but also has the effect of removing it. In other words, unlike previous drugs, it allows some hope for patient recovery. However, since it cannot restore destroyed brain cells, it is still too early to expect dramatic improvement in symptoms for patients with severe conditions.

Kisunla can be discontinued once beta-amyloid in the brain is completely removed after a certain period of administration. This increases patient convenience and reduces the financial burden of treatment. Such new drugs cost several tens of millions of KRW annually. According to the manufacturer, 69% of clinical trial participants were able to stop taking the drug within 18 months.

Will a drug surpassing Kisunla emerge in the future? Surprisingly, it might come from Korea. The domestic new drug company Aribio is developing a dementia drug called AR1001 (development code name), which acts in various ways in the human brain. It increases blood flow and reduces inflammatory substances. It inhibits the production of reactive oxygen species to prevent brain tissue damage, activates brain signaling pathways, and helps the process of neural reconnection and reorganization. This means some recovery of damaged nerves can be expected. It has the effect of removing beta-amyloid and, in addition, lowers another causative substance of dementia called tau protein. Because no drug has had such diverse mechanisms simultaneously, it has attracted considerable attention in the academic community. Phase 3 clinical trials are currently underway.

Even if AR1001’s clinical trials succeed and sales begin, the battle between Alzheimer’s and humans will not end. The emergence of more effective drugs must continue, and the challenge must persist endlessly. Facing this endless battle, a phrase resurfaces. It was the slogan Pfizer, a vaccine development company, used during the height of the COVID-19 pandemic in 2020: “Science will win.”

Jeon Seung-min, Science and Technology Writer · Editor-in-Chief of Popular Science