• 25 Sep 2024
• Admin
• News Article

Eli Lilly's Kisunla Receives Japanese Approval for Alzheimer's Disease

Eli Lilly's Kisunla receives Japanese approval for the treatment of early symptomatic Alzheimer's disease

Overview

The Ministry of Health, Labour and Welfare Japan has approved Kisunla (donanemab-azbt, 350 mg/20 mL every four weeks injection for IV infusion), Eli Lilly and Company's Alzheimer's treatment for adults with early symptomatic Alzheimer's disease (AD), which includes people with mild cognitive impairment (MCI) as well as people with the mild dementia stage of AD, with confirmed amyloid pathology.

2nd Biggest Market Approval

• Japan is the second major market in which Kisunla has been approved for use. 
• In Japan, by 2030, the number of patients with dementia is estimated to be more than 5 million, and AD is the most common cause of dementia, accounting for more than 67% of cases. 
• The number of AD patients is expected to increase significantly compared with other dementias.

From the President: Lilly International

• "Lilly scientists have been dedicated to research in Alzheimer's disease for more than 35 years, and this news is testament to their ingenuity, perseverance, 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 very meaningful results for people with early symptomatic Alzheimer's disease by significantly slowing cognitive and functional decline in our TRAILBLAZER-ALZ 2 study, which included participants from Japan. People around the world want and deserve access to treatment options for this devastating disease.” 
• “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."

Amyloid Protein

• Amyloid is a protein produced naturally in the body that can clump together to create amyloid plaques. 
• The excessive buildup of amyloid plaques in the brain may lead to memory and thinking issues associated with Alzheimer's disease. 
• Kisunla can help the body remove the excessive buildup of amyloid plaques and slow the decline that may diminish people's ability to remember new information, important dates, and appointments; plan and organize; make meals; use household appliances; manage finances; and be left alone.

Statement from Eli Lilly Japan 

• "Alzheimer's disease is a significant healthcare burden in Japan due to the rapidly aging population. We are excited to make Kisunla available in Japan as a new treatment option for early symptomatic Alzheimer's disease," said Yanping Wang, senior vice president of drug development and medical affairs at Eli Lilly Japan. 
• "Patients treated with Kisunla may have the option to stop treatment once the amyloid plaques are removed, which could help reduce the infusion burden for eligible patients."
• The application to the PMDA was based on the efficacy and safety data from TRAILBLAZER-ALZ 2 phase 3 clinical study.

TRAILBLAZER-ALZ 2 Phase 3 Study

• In the TRAILBLAZER-ALZ 2 phase 3 study, people who were the least advanced in the disease experienced the strongest results with Kisunla. 
• Trial participants were analyzed over 18 months in two groupings: one group who was less advanced in their disease (those with low to medium levels of tau protein) and the overall population, which also included participants with high tau levels. 
• Treatment with Kisunla significantly slowed clinical decline in both groups.  
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• Those individuals treated with Kisunla who were less advanced in their disease showed a significant slowing of decline of 35% compared with placebo on the integrated Alzheimer's Disease Rating Scale (iADRS), which measures memory, thinking, and daily functioning. 
• In the overall population, the response to treatment was also statistically significant using the iADRS at 22%. 
• Among the two groups analyzed, participants treated with Kisunla had up to a 39% lower risk of progressing to the next clinical stage of disease than those taking placebo.  

The Outcomes 

• Among the overall population of participants, Kisunla reduced amyloid plaques on average by 61% at 6 months, 80% at 12 months, and 84% at 18 months compared to the start of the study. 
• One of the treatment goals of the study was to remove amyloid plaques to minimal levels consistent with a visually negative scan using amyloid positron emission tomography (PET).
• If participants were confirmed to have reached these levels, they were able to complete treatment with Kisunla and switch to placebo for the remainder of the study. 
• In the TRAILBLAZER-ALZ 2 study, 66% of patients achieved plaque clearance (based on above criteria) at one year.

Kisunla’s Potential Side Effects

• Kisunla can cause amyloid-related imaging abnormalities (ARIA), which is a potential side effect with amyloid plaque-targeting therapies that does not usually cause symptoms. 
• It can be detected via magnetic resonance imaging (MRI) scans and, when it does occur, may present as temporary swelling in an area or areas of the brain, which usually resolves over time, or as small spots of bleeding in or on the surface of the brain. 
• Infrequently, larger areas of bleeding in the brain can occur. ARIA can be serious, and life-threatening events can occur. 
• Kisunla can also cause certain types of allergic reactions, some of which may be serious and life-threatening, that typically occur during infusion or within 30 minutes post-infusion. 
• Headache is another commonly reported side effect.

About Kisunla

• Kisunla (donanemab-azbt) (pronounced kih-SUHN-lah) is an amyloid-targeting treatment for people with mild cognitive impairment (MCI) as well as people with mild dementia stage of early symptomatic Alzheimer's disease, with confirmed amyloid pathology. 
• Kisunla can cause serious side effects, including amyloid-related imaging abnormalities, or ARIA, and infusion-related reactions. 
• Kisunla is a prescription medicine administered intravenously every four weeks, 700 mg for the first three doses and 1400 mg thereafter.  

About the Trial

• TRAILBLAZER-ALZ 2 (NCT04437511) is a phase 3, double-blind, placebo-controlled study to evaluate the safety and efficacy of donanemab in participants with early symptomatic Alzheimer's disease (MCI or mild dementia due to Alzheimer's disease) with the presence of confirmed Alzheimer's disease neuropathology. 
• The trial enrolled 1,736 participants, across 8 countries, selected based on cognitive assessments in conjunction evidence of Alzheimer's disease pathology. 
• The phase 3 TRAILBLAZER-ALZ 2 study results were published in the Journal of the American Medical Association (JAMA).

Lilly Study on Donanemab

Lilly continues to study donanemab in multiple clinical trials, including TRAILBLAZER-ALZ 3, which is focused on preventing symptomatic Alzheimer's disease in participants with preclinical AD; TRAILBLAZER-ALZ 5, a registration trial for early symptomatic AD currently enrolling in China and Korea; and TRAILBLAZER-ALZ 6, which is focused on expanding our understanding of ARIA through novel MRI sequences, blood-based biomarkers, and different dosing regimens of donanemab.