Lilly's Kisunla (donanemab-azbt) showed growing benefit over three years in early symptomatic Alzheimer's disease

Lilly's Kisunla (donanemab-azbt) showed growing benefit over three years in early symptomatic Alzheimer's disease

Findings from the TRAILBLAZER-ALZ 2 long-term extension study highlight Kisunla continued to demonstrate slowing of decline, with most participants having completed treatment

Data underscores the value of early intervention and supports a limited duration dosing approach with sustained long-term benefits

INDIANAPOLIS, July 30, 2025 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) announced results from the long-term extension (LTE) of the Phase 3 TRAILBLAZER-ALZ 2 study showing that participants treated with Kisunla (donanemab-azbt) demonstrated slowing of decline, a benefit that continued to grow over three years compared to an untreated external cohort from the Alzheimer's Disease Neuroimaging Initiative (ADNI).¹

Participants in the study who started treatment later still saw benefit. However, earlier initiation of Kisunla in study participants significantly reduced the risk of progression to the next stage of the disease compared to those who received Kisunla treatment later.¹ These data were shared as a late breaking 2025 Alzheimer's Association International Conference (AAIC) presentation in Toronto.

"The TRAILBLAZER-ALZ 2 long-term extension reaffirms that Kisunla delivered sustained clinical benefit that continued to increase over three years and a consistent safety profile," said Mark Mintun, M.D., group vice president, Neuroscience Research & Development, Eli Lilly and Company. "Participants continued to show meaningful outcomes, reinforcing the long-term value of early intervention."

The TRAILBLAZER-ALZ 2 LTE study was a Phase 3, double-blind extension of the original TRAILBLAZER-ALZ 2 trial, evaluating the efficacy and safety of Kisunla in individuals with early symptomatic Alzheimer's disease.¹ Participants originally treated with Kisunla either continued treatment or were switched to placebo, while those initially on placebo began Kisunla in a blinded manner. An external comparator group from ADNI was used to assess outcomes against a matched, untreated population.

Key preliminary results from the TRAILBLAZER-ALZ 2 LTE study include:

• Kisunla benefit continued to grow over three years for participants treated in the study compared to those in the matched ADNI group. Kisunla reduced cognitive decline by -0.6 at 18 months and then -1.2 at 36 months on the Clinical Dementia Rating Sum of Boxes (CDR-SB) in patients initially treated with Kisunla in the core study compared to the ADNI group.
• Earlier initiation of Kisunla reduced the risk of progression to the next stage of disease by 27% on the Clinical Dementia Rating-Global Score (CDR-G) compared to a delayed initiation Kisunla group.
• More than 75% of participants treated with Kisunla reached amyloid clearance within 76 weeks of starting treatment.
• After up to 2.5 years of observed data in participants who had completed treatment, amyloid plaque reaccumulation remained slow at a rate of approximately 2.4 CL/year, consistent with prior observations and modeling.
• No new safety signals were observed in the LTE over the three years, further reinforcing the established safety profile for Kisunla.

Amyloid-related imaging abnormalities (ARIA) with edema/effusion (ARIA-E) and with hemorrhage/with hemosiderin deposition are side effects within the class of amyloid targeting therapies that do not usually cause any symptoms, but serious and life-threatening symptoms can occur. ARIA can be fatal. Carriers of one or two copies of the apolipoprotein E ε4 (ApoE4) gene may be at higher risk of developing Alzheimer's disease and experiencing ARIA. Patients should discuss any safety concerns with their healthcare providers. 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.^2,3 Headache is another commonly reported side effect. See the Indication and Safety Summary with Warnings below for additional information.

About TRAILBLAZER-ALZ 2 Long-Term Extension (LTE) Study
Participants in the TRAILBLAZER-ALZ 2 (core) study who completed the 76-week placebo-controlled period were eligible to continue into the participant- and investigator-blinded LTE period, lasting an additional 78 weeks.

The LTE study included multiple treatment arms:

• Participants (n=550) initially treated with Kisunla in the main study either continued treatment in the LTE or were switched to placebo after meeting pre-defined amyloid clearance thresholds. These participants were followed in the LTE period to assess long-term Kisunla safety and durability of treatment effects.
• Participants receiving placebo in the main study switched to Kisunla at the start of the LTE period in a blinded manner to evaluate delayed treatment outcomes. These delayed start participants (n= 657) received Kisunla with the same dosing, administration and stopping criteria as the TRAILBLAZER-ALZ 2 trial. In the study, if the amyloid plaque level was <11 Centiloids on a single positron emission tomography (PET) scan or 11 to <25 Centiloids on 2 consecutive PET scans, the patient was eligible to be switched to placebo. For reference, <24.1 Centiloids on an amyloid PET scan is consistent with a negative visual read.

About TRAILBLAZER-ALZ 2 Study and the TRAILBLAZER-ALZ Program
TRAILBLAZER‐ALZ 2 (NCT04437511) is a multicenter, randomized, double-blind, placebo-controlled (PC) Phase 3 trial designed to assess the efficacy and safety of donanemab in participants with early symptomatic Alzheimer's disease.

Lilly continues to study donanemab in multiple clinical trials, including TRAILBLAZER-ALZ 3, which is evaluating the safety and efficacy of donanemab in patients with preclinical Alzheimer's disease to determine if it reduces risk of progression to symptomatic Alzheimer's disease. TRAILBLAZER-ALZ 5 is a registration trial for early symptomatic Alzheimer's disease currently enrolling in China, Korea, Taiwan, and other geographies. The TRAILBLAZER-ALZ 6 study recently completed the 18-month final study endpoint. Data from the study showed that a modified titration dosing schedule reduced the risk of ARIA-E compared to the TRAILBLAZER-ALZ 2 dosing regimen. These findings supported the FDA approval of an update to the U.S. prescribing information for Kisunla. This data was also presented at AAIC.

INDICATION AND SAFETY SUMMARY WITH WARNINGS

Kisunla (donanemab-azbt), pronounced kih-SUHN-lah, is used to treat adults with early symptomatic Alzheimer's disease (AD), which includes mild cognitive impairment (MCI) or mild dementia stage of disease.

Warnings - Kisunla can cause Amyloid-Related Imaging Abnormalities or "ARIA." This is a common side effect that does not usually cause any symptoms, but serious symptoms can occur. ARIA can be fatal. ARIA is most commonly seen as temporary swelling in an area or areas of the brain that usually goes away over time. Some people may also have spots of bleeding on the surface of or in the brain and infrequently, larger areas of bleeding in the brain can occur. Although most people do not have symptoms, some people have headaches, dizziness, nausea, difficulty walking, confusion, vision changes and seizures.

Some people have a genetic risk factor (homozygous apolipoprotein E ε4 gene carriers) that may cause an increased risk for ARIA. Talk to your healthcare provider about testing to see if you have this risk factor.

You may be at higher risk of developing bleeding in the brain if you take medicines to reduce blood clots from forming (antithrombotic medicines) while receiving Kisunla. Talk to your healthcare provider to see if you are on any medicines that increase this risk.

Your healthcare provider will do magnetic resonance imaging (MRI) brain scans before and during your treatment with Kisunla to check you for ARIA. You should carry information that you are receiving Kisunla, which can cause ARIA, and that ARIA symptoms can look like stroke symptoms.

Call your healthcare provider or go to the nearest hospital emergency room right away if you have any of the symptoms listed above.

There are registries that collect information on treatments for Alzheimer's disease. Your healthcare provider can help you become enrolled in these registries.

Warnings - Kisunla can cause serious allergic and infusion-related reactions. Do not receive Kisunla if you have serious allergic reactions to donanemab-azbt or any of the ingredients in Kisunla. Symptoms may include swelling of the face, lips, mouth, or eyelids, problems breathing, hives, chills, irritation of skin, nausea, vomiting, sweating, headache, or chest pain. You will be monitored for at least 30 minutes after you receive Kisunla for any reaction. Tell your healthcare provider right away if you have these symptoms or any reaction during or after a Kisunla infusion.

Other common side effects

• Headache

Tell your healthcare provider right away if you have any side effects. These are not all of the possible side effects of Kisunla. You can report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch.

Before you receive Kisunla, tell your healthcare provider:

• About all medicines you take, including prescription and over-the-counter medicines, as well as vitamins and herbal supplements. Especially tell your healthcare provider if you have medicines to reduce blood clots from forming (antithrombotic medicines, including aspirin).
• About all of your medical conditions including if you are pregnant, breastfeeding, or plan to become pregnant or breastfeed. Kisunla has not been studied in people who were pregnant or breastfeeding. It is not known if Kisunla could harm your unborn or breastfeeding baby.

How to receive Kisunla
Kisunla is a prescription medicine given through an intravenous (IV) infusion using a needle inserted into a vein in your arm. Kisunla is given once every 4 weeks. Each infusion will last about 30 minutes.

Learn more
For more information about Kisunla, call 1-800-LillyRx (1-800-545-5979) or go to kisunla.lilly.com.

This summary provides basic information about Kisunla. It does not include all information known about this medicine. Read the information given to you about Kisunla. This information does not take the place of talking with your healthcare provider. Be sure to talk to your healthcare provider about Kisunla. Your healthcare provider is the best person to help you decide if Kisunla is right for you.

Please see full Prescribing Information including boxed warning for ARIA and Medication Guide for Kisunla.

Trademarks and Trade Names
All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are references in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company's or their rights thereto. We do not intend the use or display of other companies' trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

About 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. 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 Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY

Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Kisunla (donanemab-azbt) as a treatment for people with early symptomatic Alzheimer's disease, and regulatory approval and other milestones relating to Kisunla and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study findings to date, that Kisunla will receive additional regulatory approvals or that Kisunla will be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

References

1. Eli Lilly. A Study of Donanemab (LY3002813) in Participants With Early Alzheimer's Disease (TRAILBLAZER-ALZ 2). ClinicalTrials.gov identifier: NCT04437511. Updated May 4, 2025. Accessed September 30, 2024. https://clinicaltrials.gov/study/NCT04437511.
2. Kisunla (donanemab-azbt). Prescribing Information. Lilly USA, LLC.
3. Kisunla (donanemab-azbt). Medication Guide. Lilly USA, LLC.

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SOURCE Eli Lilly and Company