Eli Lilly and Company's Kisunla™ (donanemab-azbt) has been approved by China's National Medical Products Administration (NMPA) for the treatment of early symptomatic Alzheimer's disease in adults, including those with mild cognitive impairment (MCI) and mild dementia with confirmed amyloid pathology. This marks the fourth major market approval for Kisunla, following the United States, Japan, and Great Britain.
Alzheimer's Disease in China
In China, it is estimated that nearly 6% of individuals over 65 years old are affected by Alzheimer's disease and related dementias. Projections indicate that this number could rise to almost 11% by 2050. The approval of Kisunla offers a crucial new treatment option for this growing patient population.
"Bringing Alzheimer's disease treatment options to the people facing its devastating effects is critical," said Ilya Yuffa, executive vice president and president of Lilly International, Eli Lilly and Company. "Patients and their families want and deserve access to treatment with amyloid targeting therapies, which could give them more time to do the things that matter most to them in the early symptomatic stage of the disease."
TRAILBLAZER-ALZ 2 Phase 3 Study
The NMPA's approval was primarily based on efficacy and safety data from the TRAILBLAZER-ALZ 2 Phase 3 clinical study (NCT04437511). The study involved 1,736 participants with early symptomatic Alzheimer's disease across eight countries. Results published in the Journal of the American Medical Association (JAMA) demonstrated that Kisunla significantly slowed clinical decline, particularly in participants with low to medium levels of tau protein.
Specifically, individuals treated with Kisunla who had less advanced disease showed a 35% slowing of decline compared to placebo, as measured by the integrated Alzheimer's Disease Rating Scale (iADRS). The iADRS assesses memory, thinking, and daily functioning. Furthermore, these participants had up to a 39% lower risk of progressing to the next clinical stage of the disease.
In the overall study population, Kisunla reduced amyloid plaques by an average of 61% at 6 months, 80% at 12 months, and 84% at 18 months compared to 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). Impressively, 66% of patients achieved plaque clearance within one year, allowing them to switch to placebo for the remainder of the study.
Kisunla Mechanism and Safety
Kisunla (donanemab-azbt) is an amyloid plaque-targeting therapy designed to remove the excessive buildup of amyloid plaques in the brain, which are associated with the cognitive decline seen in Alzheimer's disease. It is administered intravenously every four weeks, with an initial dose of 700 mg for the first three infusions, followed by 1400 mg thereafter.
However, Kisunla can cause amyloid-related imaging abnormalities (ARIA), a potential side effect common to amyloid plaque-targeting therapies. ARIA may manifest as temporary brain swelling or small spots of bleeding, detectable via MRI scans. While often asymptomatic, ARIA can, in rare cases, lead to serious and life-threatening events. Allergic reactions and infusion-related reactions are also potential side effects. Regular MRI monitoring is essential to manage ARIA effectively.
Ongoing Research
Eli Lilly continues to investigate donanemab in various clinical trials, including TRAILBLAZER-ALZ 3 (preclinical AD), TRAILBLAZER-ALZ 5 (registration trial in China, Taiwan, Korea, Australia, and the UK), and TRAILBLAZER-ALZ 6 (ARIA understanding). Additionally, Lilly is partnering with the DIAN-TU team to evaluate remternetug's potential in slowing or preventing amyloid plaque accumulation in early Alzheimer's disease.
