Eli Lilly and Company (NYSE: LLY) announced today that the U.S. Food and Drug Administration(FDA) has approved a label update with a new recommended titration dosing schedule for Kisunla (donanemab-azbt), Lilly's once-monthly amyloid-targeting therapy for adults with early symptomatic Alzheimer's disease (AD), which includes people with mild cognitive impairment (MCI) as well as people in the mild dementia stage of AD, with confirmed amyloid pathology..

礼来公司(NYSE: LLY) 今天宣布美国食品药品监督管理局（FDA）已批准更新Kisunla（donanemab-azbt）的标签，纳入了新的推荐滴定剂量方案。这是礼来公司每月一次针对早期症状性阿尔茨海默病（AD）成人患者的淀粉样蛋白靶向疗法，适用于经证实存在淀粉样蛋白病理的轻度认知障碍（MCI）患者以及处于阿尔茨海默病轻度痴呆阶段的人群。

In the TRAILBLAZER-ALZ 6 study, the modified titration schedule significantly lowered the incidence of amyloid-related imaging abnormalities with edema/effusion (ARIA-E) versus the original dosing schedule at 24 and 52 weeks, while still achieving similar levels of amyloid plaque removal and P-tau217 reduction..

在TRAILBLAZER-ALZ 6研究中，与原始剂量方案相比，改良的滴定方案在24周和52周显著降低了与淀粉样蛋白相关的影像学异常伴水肿/渗出（ARIA-E）的发生率，同时仍实现了相似水平的淀粉样蛋白斑块清除和P-tau217降低。

'We are confident that this label update for Kisunla will significantly aid healthcare professionals in evaluating appropriate treatment options for their patients,' stated

“我们相信，Kisunla的这一标签更新将大大帮助医疗专业人员评估患者的适当治疗方案，”

Brandy Matthews

白兰地·马修斯

, MD, FAAN, Lilly's Vice President of Global & US Medical Affairs for Alzheimer's Disease. 'This update underscores our unwavering commitment to patient safety and the advancement of Alzheimer's disease treatment by potentially mitigating the risk of ARIA-E.'

医学博士，FAAN，礼来公司全球及美国阿尔茨海默病医学事务副总裁。'此次更新强调了我们对患者安全和推进阿尔茨海默病治疗的坚定承诺，有可能降低ARIA-E的风险。'

The new recommended dosing regimen involves a more gradual titration, and the TRAILBLAZER-ALZ 6 study significantly lowered the incidence of ARIA-E by 41% at 24 weeks and by 35% at 52 weeks versus the original dosing schedule. ARIA-E is a side effect of amyloid plaque-targeting therapies, including Kisunla.

新的推荐剂量方案涉及更为渐进的滴定，与原始剂量计划相比，TRAILBLAZER-ALZ 6 研究在第24周显著降低了ARIA-E的发生率41%，在第52周降低了35%。ARIA-E 是靶向淀粉样蛋白斑块疗法（包括Kisunla）的一种副作用。

ARIA-E is usually asymptomatic, although serious and fatal events can occur. The new dosing recommendation differs from the original dosing by shifting a single vial from the first dose to the third dose, delivering the same amount of Kisunla by week 24. This resulted in lower rates of ARIA-E without compromising Kisunla's ability to reduce amyloid plaque or Kisunla's once-monthly dosing with the potential for limited-duration treatment based on amyloid plaque removal to minimal levels..

ARIA-E 通常无症状，尽管也可能发生严重和致命的事件。新的剂量建议将第一剂的一小瓶药转移到第三剂，与原始剂量不同，在第24周时仍提供相同量的Kisunla。这降低了ARIA-E的发生率，同时没有影响Kisunla减少淀粉样蛋白斑块的能力，也没有改变Kisunla每月一次的给药方案，且有可能根据淀粉样蛋白斑块降至最低水平进行有限疗程的治疗。

Key findings from the TRAILBLAZER-ALZ 6 study, which supports this label update, included:

支持这一标签更新的TRAILBLAZER-ALZ 6研究的主要发现包括：

The primary endpoint of the study was the proportion of participants with any occurrence of ARIA-E by week 24. The results showed the incidence of ARIA-E was 14% in patients receiving the modified titration compared with 24% for those receiving the original dosing regimen, a 41% lower relative risk..

研究的主要终点是到第24周时出现任何ARIA-E的参与者比例。结果显示，接受改良滴定的患者ARIA-E的发生率为14%，而接受原始剂量方案的患者为24%，相对风险降低了41%。

At week 52, the incidence of ARIA-E was 16% in patients receiving the modified titration compared with 25% for those receiving the original dosing regimen, a 35% lower relative risk.

在第52周时，接受调整后滴定方案的患者中ARIA-E的发生率为16%，而接受原剂量方案的患者为25%，相对风险降低了35%。

Including asymptomatic radiographic events at week 52, ARIA, ARIA-E, and ARIA-H were observed in 29%, 16%, and 25% of patients receiving the modified titration dosing. ARIA-E and ARIA-H are different types of amyloid-related imaging abnormalities (ARIA). ARIA with edema is characterized as ARIA-E and ARIA with hemosiderin deposition is characterized as ARIA-H..

在第52周包括无症状的影像学事件，接受改良滴定剂量的患者中，有29%、16%和25%分别观察到ARIA、ARIA-E和ARIA-H。ARIA-E和ARIA-H是不同类型的淀粉样蛋白相关影像学异常（ARIA）。伴有水肿的ARIA被定义为ARIA-E，而伴有含铁血黄素沉积的ARIA被定义为ARIA-H。

Patients on the modified titration experienced a reduction of amyloid plaque and P-tau217 comparable to patients receiving the original dosing regimen. As observed using amyloid PET at the primary endpoint of 24 weeks, amyloid plaque levels in patients on the modified titration of donanemab in TRAILBLAZER-ALZ 6 were reduced on average 67% from baseline compared to 69% for patients on the original dosing regimen..

接受改良滴定方案的患者淀粉样蛋白斑块和P-tau217的减少程度与接受原始剂量方案的患者相当。通过在24周主要终点时的淀粉样蛋白PET观察，TRAILBLAZER-ALZ 6试验中接受改良滴定方案的donanemab治疗的患者，其淀粉样蛋白斑块水平较基线平均减少了67%，而接受原始剂量方案的患者减少了69%。

7,8

7,8

No new adverse reactions were identified in this study, although higher rates of hypersensitivity reactions and infusion-related reactions were observed.

本研究未发现新的不良反应，但观察到较高的超敏反应和输注相关反应发生率。

'This updated dosing strategy is a meaningful advancement for patients and their care teams,' said Elly Lee, MD, Chief Medical Officer and Principal Investigator,

“这种更新的剂量策略对患者及其护理团队来说是一个有意义的进步，”医学博士Elly Lee（首席医疗官兼首席研究员）表示。

Irvine Center for Clinical Research

欧文临床研究中心

. 'By significantly reducing the risk of ARIA-E, we can offer patients and care teams greater confidence in the safety of Kisunla while preserving its ability to reduce amyloid.'

“通过显著降低ARIA-E的风险，我们可以在保持Kisunla减少淀粉样蛋白能力的同时，为患者和护理团队提供更大的安全保障。”

The

The

U.S.

美国

FDA approved Kisunla in

FDA 批准了 Kisunla

July 2024

2024年7月

based on the TRAILBLAZER-ALZ 2 Phase 3 clinical trial data. The study demonstrated that Kisunla significantly slowed cognitive and functional decline in patients who were less pathologically advanced in their disease by up to 35% and by 22% in the overall study population compared to placebo at 18 months..

基于TRAILBLAZER-ALZ 2 III期临床试验数据。研究表明，与安慰剂相比，Kisunla在18个月内显著减缓了病理进展较轻的患者的认知和功能下降达35%，在整个研究人群中则减缓了22%。

Kisunla reduced the risk of progressing to the next clinical stage of disease by 37% over the same period.

基苏拉在同一时期将疾病进展到下一临床阶段的风险降低了37%。

Cognitive and functional decline was characterized by more severe memory and thinking problems, more trouble with daily activities, and a greater need for help from caregivers.

认知和功能下降的特征是更严重的记忆和思维问题、日常活动更困难，以及对照顾者帮助的需求更大。

for Kisunla is dedicated to assisting patients throughout their treatment journey with Kisunla. This free program provides essential services, including coverage determination assistance, care coordination, nurse navigator support, and personalized resources. For more information about Lilly Support Services and Kisunla, visit .

对于Kisunla，该计划致力于在整个治疗过程中为使用Kisunla的患者提供帮助。这个免费项目提供关键服务，包括覆盖范围确认协助、护理协调、护士导航支持以及个性化资源。如需更多关于Lilly支持服务和Kisunla的信息，请访问。

About Kisunla™ (donanemab)

关于Kisunla™（donanemab）

Kisunla™ (donanemab-azbt) (pronounced kih-SUHN-lah) is an amyloid-targeting therapy 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 (donanemab-azbt) injection for intravenous use is available as a 350 mg/20 mL single-dose vial.

Kisunla™（donanemab-azbt）（发音为 kih-SUHN-lah）是一种针对淀粉样蛋白的疗法，适用于患有轻度认知障碍（MCI）以及早期症状性阿尔茨海默病轻度痴呆阶段且确诊存在淀粉样蛋白病理的患者。Kisunla（donanemab-azbt）注射液用于静脉注射，提供350毫克/20毫升的单剂量瓶装形式。

Kisunla can cause serious side effects, including amyloid-related imaging abnormalities, or ARIA, and infusion-related reactions..

基苏努单抗可引起严重副作用，包括与淀粉样蛋白相关的影像学异常（ARIA）和输液相关反应。

About TRAILBLAZER-ALZ 6 study and the TRAILBLAZER-ALZ program

关于TRAILBLAZER-ALZ 6研究和TRAILBLAZER-ALZ项目

TRAILBLAZER-ALZ 6 (

TRAILBLAZER-ALZ 6 (

NCT05738486

NCT05738486

) is a Phase 3b, multicenter, randomized, double-blind study to investigate different dosing regimens and their effect on ARIA-E in adults with early symptomatic Alzheimer's disease. The trial enrolled 843 participants ages 60-85 selected based on cognitive assessments in conjunction with amyloid plaque imaging by PET scan..

）是一项针对早期症状性阿尔茨海默病成人患者的不同剂量方案及其对ARIA-E影响的IIIb期、多中心、随机、双盲研究。试验招募了843名年龄在60-85岁的参与者，这些参与者是通过认知评估结合PET扫描的淀粉样蛋白斑块成像选出的。

Alzheimer's and Dementia

阿尔茨海默病与痴呆症

About TRAILBLAZER-ALZ 2 study

关于TRAILBLAZER-ALZ 2研究

TRAILBLAZER-ALZ 2 (

TRAILBLAZER-ALZ 2 (

NCT04437511

NCT04437511

) is a Phase 3, randomized, 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 with evidence of Alzheimer's disease pathology.

）是一项三期、随机、双盲、安慰剂对照研究，旨在评估donanemab在早期症状性阿尔茨海默病（轻度认知障碍或由阿尔茨海默病引起的轻度痴呆）且经确认存在阿尔茨海默病神经病理学特征的参与者中的安全性和有效性。该试验在8个国家招募了1736名参与者，这些参与者通过认知评估并结合阿尔茨海默病病理学证据进行筛选。

The Phase 3 TRAILBLAZER-ALZ 2 study results were .

第三阶段TRAILBLAZER-ALZ 2研究结果是。

Journal of the American Medical Association

美国医学协会期刊

Lilly continues to study donanemab in multiple clinical trials, including TRAILBLAZER-ALZ 3, evaluating the potential to reduce the risk of progression to symptomatic AD in participants with preclinical AD; and TRAILBLAZER-ALZ 5, a registration trial for early symptomatic AD currently enrolling in

礼来公司继续在多项临床试验中研究donanemab，包括TRAILBLAZER-ALZ 3，评估其降低前临床AD参与者进展为有症状AD风险的潜力；以及TRAILBLAZER-ALZ 5，一个针对早期有症状AD的注册试验，目前正在招募中。

About Lilly

关于Lilly

Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases.

礼来是一家医药公司，将科学转化为治愈手段，以改善世界各地人们的生活。近150年来，我们一直致力于开创改变生命的发现，如今我们的药物已帮助全球数千万人。通过利用生物技术、化学和基因医学的力量，我们的科学家正在加速推进新的发现，以解决一些全球最重要的健康挑战：重新定义糖尿病护理；治疗肥胖症并遏制其最具破坏性的长期影响；推动对抗阿尔茨海默病的斗争；为一些最严重的免疫系统疾病提供解决方案；并将最难治疗的癌症转变为可管理的疾病。

With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit .

每迈向更健康的世界一步，我们都受到一个目标的激励：让数百万人的生活更美好。这包括开展反映世界多样性的创新临床试验，并努力确保我们的药品可及且负担得起。欲了解更多信息，请访问。