Leqembi (lecanemab), a therapy that directly removes the pathogenic protein driving Alzheimer's disease and slows disease progression, is opening a new treatment paradigm in a super-aged society.

Unlike existing drugs that primarily focused on symptomatic relief, Leqembi has demonstrated disease-modifying potential, signaling broad changes across clinical practice and policy.

Dailypharm spoke with Professor Min-young Chun, neurologist at Yongin Severance Hospital, regarding Leqembi’s long-term evidence, real-world clinical implications, and the importance of early diagnosis and early intervention in Alzheimer's disease.

“Leqembi delays disease progression by one year, which is a significant extension in the survival period”

Leqembi is the first disease-modifying treatment to emerge in the field of Alzheimer's disease, which had seen no new drugs for over 20 years.

Since the 1990s and early 2000s, there have been almost no new drugs developed for Alzheimer's disease, resulting in a prolonged 20-year innovation gap without any new drug approvals.

While existing drugs focus on symptom relief, Leqembi is drawing attention for its mechanism that directly removes amyloid beta to slow the fundamental progression of the disease.

Professor Chun stated, “Leqembi is the first treatment option that directly targets amyloid beta to slow the fundamental progression of the disease, marking a significant advancement that ends the 20-year gap in new drug development.”

She further explained, “In the recently published 4-year long-term analysis, the Leqembi treatment group showed a delay in disease progression of approximately one year compared to the natural decline in Alzheimer's disease. Based on the CDR-SB score, it was 1.75 points lower versus ADNI and 2.17 points lower versus BioFINDER.”

Furthermore, no new safety concerns were observed during the 4-year OLE study, and the ARIA incidence rate decreased after the initial 12 months of treatment and remained stable without significant change over the 4 years.

Professor Chun emphasized, “Some may underestimate a one-year delay, but just as a 6-month survival gain in oncology is considered a meaningful outcome, delaying the time when independent daily living becomes impossible by even one year holds immense value.”

Lower ARIA rate in Asians…Will also strengthen domestic monitoring system

As Leqembi has not been released in Korea for long, sufficient data has not yet accumulated to yield statistically significant results.

Concerns also exist regarding the management of amyloid-related imaging abnormalities (ARIA), the most notable adverse reaction requiring caution during Leqembi treatment.

On this, Professor Chun explained, “ARIA-E occurred in 6.2% and ARIA-H in 14.4% of Asian patients %, lower than the overall population. This could be attributed to complex factors like differences in APOE ε4 gene frequency or drug dosage variations due to body weight.”

She further noted, “South Korea has well-established imaging infrastructure, including MRI and PET, enabling systematic monitoring before and after administration. This environment supports the safe use of new drugs like Leqembi.”

According to Professor Chun, the Asian subgroup analysis of Leqembi’s Phase III Clarity AD clinical trial showed an ARIA-E incidence rate of 6.2% in Asians, lower than the 12.6% rate in the overall population. The ARIA-H incidence rate was also lower in Asians at 14.4%, compared to 17.3% in the overall population.

She added, “Adverse reactions are being closely managed through regular monitoring. When they occur, treatment is guided by established medication-related guidelines. Currently, multiple institutions are compiling and analyzing Leqembi treatment data, and clearer results are expected as early as the beginning of next year.

Regarding the approval of the subcutaneous (SC) maintenance therapy formulation in the U.S., Professor Chun noted, “The Leqembi SC formulation offers similar efficacy to the intravenous (IV) formulation while having a lower incidence of infusion-related adverse events. This allows patients or caregivers to administer the drug themselves, offering significant advantages in terms of accessibility and compliance.”

“Early diagnosis and treatment of Alzheimer's reduces socioeconomic burden”

With South Korea entering a super-aged society, dementia has emerged as a socioeconomic challenge beyond an individual disease. Professor Chun emphasized that advancing the timing of treatment is key to reducing the national burden.

She stated, “Domestic dementia care costs approximately KRW 25 trillion annually. Delaying progression to severe stages through early diagnosis and treatment can significantly reduce long-term care and medical expenditure.”

Long-term simulation data showed Leqembi confirmed such an effect. Leqembi delayed progression to mild-and-moderate stages by 2.7 years and 2.9 years, respectively — supporting meaningful savings in healthcare costs.

Regarding this, Professor Chun explained, “These results can enhance the efficiency of the dementia management system and positively impact national healthcare finances.”

Institutional challenges remain. The treatment remains non-reimbursed, and while MRI scans are covered, amyloid PET scans remain non-reimbursed, resulting in patient out-of-pocket costs.

Professor Chun noted, “Beyond amyloid, the long-term therapeutic effect of new drugs like Leqembi is more pronounced in patients with lower tau protein accumulation. As Alzheimer's disease progresses, tau protein accumulation increases. Therefore, I believe it would be efficient to prioritize coverage for the early stages when tau levels are lower.”

Professor Chun further explained, “We are conducting amyloid PET scans to compare how much amyloid is removed before and after Leqembi administration, but this process incurs significant cost burdens. If amyloid PET scans were covered, it would greatly aid patients in receiving early diagnosis and treatment.”

Finally, Professor Chun reiterated the necessity of early intervention for Alzheimer's disease.

Professor Chun added, “Early detection and intervention are paramount for Alzheimer's disease, yet some delay hospital visits due to fear of dementia diagnosis. The sooner diagnosis and treatment occur, the greater the effect. If treatments become reimbursed, it would alleviate household medical expenses and could positively impact socioeconomic aspects and reduce national healthcare costs in the long term.”