The Ministry of Health, Labour and Welfare of Japan has approved Kisunla™ (donanemab-azbt, 350 mg/20 mL injection for IV infusion every four weeks), Eli Lilly and Company’s (NYSE: LLY) treatment for early symptomatic Alzheimer’s disease (AD). This includes patients with mild cognitive impairment (MCI) and those in the mild dementia stage of AD with confirmed amyloid pathology.
Japan is now the second major market to approve Kisunla. By 2030, Japan is projected to have over 5 million dementia patients, with Alzheimer’s disease being the leading cause, responsible for over 67% of dementia cases. The number of AD patients is expected to increase significantly in comparison to other forms of dementia.
“Lilly scientists have dedicated over 35 years to Alzheimer’s research, and this approval is a testament to their innovation, persistence, and commitment to helping people with this disease,” said Ilya Yuffa, executive vice president and president of Lilly International, Eli Lilly and Company. “Kisunla demonstrated meaningful results for those with early symptomatic Alzheimer’s by significantly slowing cognitive and functional decline in our TRAILBLAZER-ALZ 2 study, which included Japanese participants. This approval is a critical step toward providing patients access to these first-of-its-kind amyloid therapies, which may give them more time to do what matters most to them.”
Amyloid is a naturally occurring protein that can form plaques in the brain, contributing to memory and thinking problems associated with Alzheimer’s disease. Kisunla helps remove these plaques, potentially slowing the decline in memory, daily functioning, and other cognitive abilities such as organizing, managing finances, and preparing meals.
“With Japan’s rapidly aging population, Alzheimer’s disease presents a significant healthcare challenge. We are thrilled to bring Kisunla to Japan as a new treatment option for early symptomatic AD,” said Yanping Wang, senior vice president of Drug Development and Medical Affairs at Eli Lilly Japan. “Patients treated with Kisunla may stop treatment once amyloid plaques are cleared, which could help reduce the burden of ongoing infusions for eligible patients.”
TRAILBLAZER-ALZ 2 Phase 3 Study Results
The approval in Japan is based on data from the TRAILBLAZER-ALZ 2 Phase 3 clinical study, which assessed the efficacy and safety of Kisunla.
In this study, participants at earlier stages of the disease showed the strongest response to Kisunla. Over 18 months, two groups were analyzed: those with low to medium levels of tau protein (an indicator of disease progression) and the overall population, which also included participants with high tau levels. In both groups, Kisunla significantly slowed clinical decline.
In those with less advanced disease, Kisunla slowed decline by 35% compared to placebo, measured by the integrated Alzheimer’s Disease Rating Scale (iADRS), which evaluates memory, thinking, and daily function. In the overall population, a 22% slowing of decline was observed, also statistically significant. Additionally, participants treated with Kisunla had up to a 39% lower risk of progressing to the next clinical stage of the disease compared to those on placebo.
Kisunla reduced amyloid plaques by an average of 61% at six months, 80% at 12 months, and 84% at 18 months. A key goal of the study was to achieve minimal amyloid levels based on amyloid PET scans. Once participants reached these levels, they were eligible to switch from Kisunla to placebo for the remainder of the study. In the TRAILBLAZER-ALZ 2 study, 66% of participants achieved plaque clearance at one year.
Potential Side Effects
Kisunla may cause amyloid-related imaging abnormalities (ARIA), a known side effect of amyloid plaque-targeting therapies. ARIA can be detected via MRI and often presents as temporary brain swelling, which typically resolves over time, or as small spots of bleeding in or on the surface of the brain. In rare cases, larger areas of bleeding may occur. While ARIA is usually asymptomatic, it can be serious, and life-threatening events are possible. Kisunla can also cause allergic reactions, including serious and potentially life-threatening reactions that may occur during or shortly after the infusion.
