Eli Lilly has secured approval from the Ministry of Health, Labour and Welfare (MHLW) in Japan for Kisunla (donanemab-azbt) as a treatment for early symptomatic Alzheimer's disease. This includes patients with mild cognitive impairment (MCI) and those in the mild dementia stage, provided they have confirmed amyloid pathology. The approval marks Japan as the second major market for Kisunla, following the United States. This development offers a new therapeutic avenue for a nation grappling with an aging population and a growing prevalence of dementia.
TRAILBLAZER-ALZ 2 Study Results
The approval is underpinned by data from the Phase III TRAILBLAZER-ALZ 2 clinical study, a double-blind, placebo-controlled trial involving 1,736 participants with early symptomatic Alzheimer's across eight countries. The study assessed the efficacy and safety of donanemab, with findings indicating that patients in the earliest stages of the disease experienced the most significant benefits.
Participants were monitored over 18 months and divided into two cohorts: those less advanced in their disease progression (low to medium levels of tau protein) and the overall population, which included individuals with higher tau levels. Kisunla demonstrated a significant reduction in clinical decline in both cohorts. Specifically, in the less advanced group, the treatment reduced the risk of disease progression to the next clinical stage by 35% compared to placebo, as measured by the integrated Alzheimer's Disease Rating Scale (iADRS).
In the broader participant group, Kisunla reduced amyloid plaques by 61% at six months, 80% at 12 months, and 84% at 18 months from baseline. A key treatment goal was to reduce amyloid plaques to minimal levels, consistent with a visually negative scan using amyloid positron emission tomography (PET). In the TRAILBLAZER-ALZ 2 study, 66% of patients achieved plaque clearance at one year, allowing them to switch to placebo for the remainder of the study.
Clinical Implications and Safety Profile
Yanping Wang, senior vice president of Drug Development and Medical Affairs at Eli Lilly Japan, noted that patients treated with Kisunla may have the option to stop treatment once amyloid plaques are removed, potentially reducing the infusion burden. However, Kisunla is associated with potential side effects, including amyloid-related imaging abnormalities (ARIA) and infusion-related reactions, necessitating careful monitoring.
ARIA, a potential side effect of amyloid plaque-targeting therapies, may manifest as temporary brain swelling or small spots of bleeding, detectable via MRI scans. While often asymptomatic, ARIA can, in rare instances, lead to serious and life-threatening events. The prescribing information for Kisunla includes a boxed warning regarding the risk of ARIA, similar to other amyloid-targeting therapies like Leqembi.
Alzheimer's Disease in Japan
Alzheimer's disease poses a significant healthcare challenge in Japan, with estimates suggesting that over 5 million people will be living with dementia by 2030. Alzheimer's accounts for approximately 67% of dementia cases in the country, and its prevalence is expected to rise significantly with the aging population. The approval of Kisunla offers a crucial new treatment option for this growing patient population.
Ilya Yuffa, executive vice president and president of Lilly International, emphasized the importance of this approval, stating, "Today's news is another critical step in ensuring patients with Alzheimer's disease can receive treatment with these first class of amyloid therapies, which could give them more time to do what matters most to them."
