Korean Dementia Association Addresses Leqembi Safety Concerns, Cites Lower Side Effect Incidence in East Asians
Key Insights
The Korean Dementia Association addressed concerns over Leqembi's safety, emphasizing that side effects like brain hemorrhage and edema are rare, particularly in East Asians.
Phase 3 trial data involving Korean participants showed a lower incidence of amyloid-related imaging abnormality-edema (ARIA-E) at 5.6%, compared to 12.6% overall.
Leqembi, co-developed by Eisai and Biogen, received approval in South Korea for treating mild cognitive impairment and early-stage Alzheimer's disease, despite EU and Australian rejections.
The Korean Dementia Association has moved to allay safety concerns surrounding the Alzheimer’s treatment Leqembi (lecanemab), which is slated for domestic release in South Korea. According to the association, the side effects associated with the drug are not significant enough to warrant major concern.
At a press conference coinciding with the Fall Academic Conference of the Korean Dementia Association, Chairperson Choi Sung-hye (professor of neurology at Inha University Hospital) acknowledged concerns about potential side effects such as brain hemorrhage and cerebral edema. However, she emphasized that such occurrences are rare.
Leqembi, developed through a collaboration between Eisai and Biogen, is an amyloid beta antibody treatment designed to slow the progression of Alzheimer’s disease (search). It functions by targeting and preventing the accumulation of neurotoxic amyloid beta protein (search) in the brain.
Leqembi's Clinical Trial Results and Regulatory Approvals
Phase 3 clinical trial results (Clarity AD) indicated that Leqembi delayed Alzheimer’s progression by 27%. Based on these findings, South Korea’s Ministry of Food and Drug Safety (MFDS) approved the drug in May for adults experiencing mild cognitive impairment and early-stage Alzheimer’s. Leqembi, administered biweekly via intravenous injection, has also secured approval in the U.S., Japan, and China.
Safety Concerns and International Regulatory Scrutiny
Despite approvals in several countries, the European Union (EU) and Australia have declined to approve Leqembi, raising safety questions. The European Medicines Agency (EMA) recommended against market authorization due to amyloid-related imaging abnormalities (ARIA) observed in MRI scans during clinical trials, indicating temporary brain swelling. The EMA reported instances of brain hemorrhages requiring hospitalization and three deaths linked 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 safety risks, particularly ARIA cases.
Korean Experts Address Safety and Efficacy
Chairperson Choi addressed these concerns, stating that the incidence of side effects like brain hemorrhage or cerebral edema is low, and even lower among East Asians. In the Phase 3 trial involving 1,795 participants, 26.4% experienced allergic reactions overall, 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.
Cost and Access Considerations
Chairperson Choi also voiced concerns about the high cost of Leqembi due to the absence of insurance coverage. In Japan, the annual treatment cost is approximately 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."
Korean Phase 3 Results: Fewer Side Effects
Professor Park Ki-hyung (Gachon University Gil Medical Center) presented Phase 3 trial results specific to Korean participants, marking the first disclosure of data for this subgroup. The data indicated that while results were generally consistent with other groups, side effects were less frequent in Koreans. The incidence of amyloid-related imaging abnormality-edema (ARIA-E) was notably lower.
In the Phase 3 trial, adverse drug reactions were observed in 26.4% of all participants, but only 13% of Koreans and 10% of Japanese participants experienced these reactions. Professor Park noted that most cases in Koreans were Grade 1, resolving 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 stated.
For ARIA-H, which includes microhemorrhages and hemosiderosis, the incidence in Koreans was lower than the overall group, with no symptomatic cases reported. Professor Park suggested that the reasons for this trend are unclear and require further investigation, possibly due to the relatively small sample size of the Korean population.