Korean Dementia Association: “Leqembi's Side Effects Are Not Significant”

The Korean Dementia Association has addressed safety concerns related to the upcoming domestic release of the Alzheimer’s treatment Leqembi (ingredient: lecanemab), stating that the side effects are not significant enough to be worrisome.

At a press conference held on the 2nd in conjunction with the Fall Academic Conference of the Korean Dementia Association at the Baekbeom Kim Koo Memorial Hall, Chairperson Choi Sung-hye (professor of neurology at Inha University Hospital) noted, “While there are concerns about side effects such as brain hemorrhage and cerebral edema, these cases are rare.”

Leqembi, co-developed by Eisai and Biogen, is an amyloid beta antibody treatment designed to slow the progression of Alzheimer’s by preventing the accumulation of neurotoxic amyloid beta protein in the brain.

Phase 3 clinical trial results (Clarity AD) showed that Leqembi delayed Alzheimer’s progression by 27%. Recognizing these findings, Korea’s Ministry of Food and Drug Safety (MFDS) approved the drug in May for the treatment of adults with mild cognitive impairment and early-stage Alzheimer’s disease. Administered biweekly as an intravenous injection, Leqembi has also been approved in the U.S., Japan, and China.

However, concerns over its safety arose when the European Union (EU) and Australia declined to approve it. In July, the European Medicines Agency (EMA) recommended against its market authorization due to amyloid-related imaging abnormalities (ARIA) seen in MRI scans during clinical trials, which showed temporary brain swelling. According to the EMA, some patients experienced brain hemorrhages severe enough to require hospitalization, and there were three additional deaths due to brain hemorrhage and edema during trials. Australia’s Therapeutic Goods Administration (TGA) also denied approval, citing that the drug’s efficacy did not outweigh its safety risks, particularly mentioning ARIA cases.

Criticism also surfaced in South Korea regarding the MFDS’s decision to approve the drug without a review by the Central Pharmaceutical Affairs Advisory Committee, adding to the scrutiny as Leqembi nears its domestic launch.

Addressing these concerns, Chairperson Choi stated, “There are not many cases of side effects like brain hemorrhage or cerebral edema, and in East Asians, the incidence of side effects was about half.”

According to Choi, in the Phase 3 trial involving 1,795 participants, 26.4% experienced allergic reactions, but the rate was only 12.4% among Asians, including 128 Korean participants. The incidence of cerebral edema was 12.6% overall, but only 6.5% among Asian participants.

Chairperson Choi expressed concern over the drug’s high cost due to the lack of insurance coverage. In Japan, for example, annual treatment costs around KRW 27 million (USD 20,300).

“Besides the high price, domestic experts have limited experience with the drug, which may raise questions about its effectiveness,” Choi added. “While the association considers these factors, we will support the smooth introduction of this first-of-its-kind treatment in Korea.”

Initial Disclosure of Korean Phase 3 Results for Leqembi: Fewer Side Effects Observed in Koreans

During the conference, Professor Park Ki-hyung (Gachon University Gil Medical Center) presented the results of the Phase 3 trial involving Korean participants. This marked the first disclosure of data specific to the Korean subgroup.

According to the data, while results were generally consistent with other groups, side effects appeared less frequently in Koreans. Notably, the incidence of amyloid-related imaging abnormality-edema (ARIA-E), characterized by vascular swelling and effusion outside the blood vessels, was lower, suggesting the need for further research.

In the Phase 3 trial, adverse drug reactions were observed in 26.4% of participants overall, but only 13% of Koreans and 10% of Japanese participants experienced these reactions. Professor Park stated, “Most cases in Koreans were Grade 1, meaning issues could resolve on their own or with treatment within 24 hours.”

The incidence of ARIA-E was 12.6% overall, but only 5.6% among Korean participants. “There was a trend of ARIA-E being less common in Asians, and symptoms were generally mild,” Park noted.

For ARIA-H, which includes microhemorrhages and hemosiderosis (excess iron deposition), the incidence in Koreans was lower than the overall group, with no symptomatic cases reported.

On these findings, Professor Park remarked, “It is difficult to determine the exact reason for this trend, and further research is necessary. It may be due to the relatively small sample size of the population.”