Lilly’s Kisunla™ (donanemab-azbt) Approved By The FDA For The Treatment Of Early Symptomatic Alzheimer’s Disease

SOUTH CAROLINA – July 23, 2024 –  The U.S. Food and Drug Administration (FDA) approved Kisunla™ (donanemab-azbt, 350 mg/20 mL once-monthly injection for IV infusion), Eli Lilly and Company’s (NYSE: LLY) 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.^{1, 2} Once-monthly Kisunla is the first and only amyloid plaque-targeting therapy with evidence to support stopping therapy when amyloid plaques are removed, which can result in lower treatment costs and fewer infusions.^3-6 

“Kisunla demonstrated very meaningful results for people with early symptomatic Alzheimer’s disease, who urgently need effective treatment options. We know these medicines have the greatest potential benefit when people are treated earlier in their disease, and we are working hard in partnership with others to improve detection and diagnosis,” said Anne White, executive vice president and president of Lilly Neuroscience, Eli Lilly and Company. “Our deepest thanks to the patients and their loved ones for participating in our clinical programs and to Lilly scientists and collaborators persevering over decades of research. Each year, more and more people are at risk for this disease, and we are determined to make life better for them.”

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.^{7, 8} 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.^{1, 7-9}

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.^{1, 10, 11} Treatment with Kisunla significantly slowed clinical decline in both groups.¹ 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%.^1, 12 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.¹³

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.^{1, 14} 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.

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.^1, 2 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. See the Indication and Safety Summary with Warnings below for additional information. 

“This approval marks another step forward in evolving the standard of care for people living with Alzheimer’s disease that will ultimately include an arsenal of novel treatments, providing much needed hope to the Alzheimer’s community. As a physician, I am encouraged by the potential to stop treatment, which could reduce out-of-pocket costs and infusion burden for eligible patients,” said Howard Fillit, M.D., Co-Founder and Chief Science Officer at the Alzheimer’s Drug Discovery Foundation (ADDF). “Diagnosing and treating Alzheimer’s sooner than we do today has the potential to meaningfully slow disease progression, giving patients invaluable time to maintain their independence for longer.”

Cost and Coverage

In the TRAILBLAZER-ALZ 2 trial, people were able to complete treatment and switch to placebo at 6, 12, or 18 months after they achieved one of the study’s treatment goals, minimal levels of amyloid plaque consistent with a visually negative amyloid PET scan. In the overall population of people receiving Kisunla, 17% completed treatment at 6 months, 47% at 12 months, and 69% at 18 months based on an assessment of amyloid levels via an amyloid PET scan.¹ 

The total cost of Kisunla will vary by patient based on when they complete treatment. The FDA’s dosing instructions state that prescribers can consider stopping the dosing of Kisunla based on removal of amyloid plaques to minimal levels as observed on amyloid PET imaging. The potential to complete treatment after a limited-duration course of therapy, along with 30-minute infusions once per month, could result in lower patient out-of-pocket treatment costs and fewer infusions compared to other amyloid-targeting therapies.⁶ 

Patients’ out-of-pocket cost for treatment with Kisunla will depend on their length of treatment and their insurance. Coverage and reimbursement for Kisunla are now available for eligible patients on Medicare under a National Coverage Determination with Coverage with Evidence Development. Also, as of October 2023, broad coverage and reimbursement for amyloid PET scans are available for eligible patients on Medicare. More than 98% of eligible Medicare patients have coverage that eliminates, limits, or caps their annual out-of-pocket exposure.¹⁵ 

Lilly Support Services for Kisunla is a free support program committed to helping patients navigate treatment with Kisunla. The program includes offerings such as coverage determination assistance, care coordination, nurse navigator support, and customized support and resources. For more information about Lilly Support Services and Kisunla, visit www.Kisunla.Lilly.com or call 1-800-LillyRx (1-800-545-5979).

Lilly Donating to Lilly Cares Foundation
Lilly intends to donate Kisunla to the Lilly Cares Foundation, a separate nonprofit organization that makes medicines available at no cost to qualified Americans, including some Medicare beneficiaries, who meet financial eligibility and other criteria. This is consistent with Lilly’s long history of supporting access to our products to patients with financial need through medication donations to charitable organizations. Learn more about the Lilly Cares Foundation, including eligibility criteria, at www.lillycares.com. 

A media kit is available on Lilly.com with additional resources. 

About Kisunla™ (donanemab-azbt)
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 TRAILBLAZER-ALZ 2 Study and the TRAILBLAZER-ALZ Program
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 with 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 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.

References 

1. Kisunla (donanemab-azbt). Prescribing Information. Lilly USA, LLC. 
2. Kisunla (donanemab-azbt). Medication Guide. Lilly USA, LLC. 
3. Sims JR, Zimmer JA, Evans CD, et al. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. 2023;330(6):512-527. doi:10.1001/jama.2023.13239.
4. Ross EL, Weinberg MS, Arnold SE. Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease in the US. JAMA Neurol. 2022;79(5):478-487. doi:10.1001/jamaneurol.2022.0315.
5. Boustani M, Doty EG, Garrison LP Jr, et al. Assessing the Cost-effectiveness of a Hypothetical Disease-modifying Therapy With Limited Duration for the Treatment of Early Symptomatic Alzheimer Disease. Clin Ther. 2022;44(11):1449-1462. doi:10.1016/j.clinthera.2022.09.008.
6. Mattke S, Ozawa T and Hanson M. Implications of Treatment Duration and Intensity on the Value of Alzheimer’s Treatments. Clinical Trials on Alzheimer’s Disease. Oct. 24-27, 2023.
7. Porsteinsson AP, Isaacson RS, Knox S, et al. Diagnosis of early Alzheimer’s disease: clinical practice in 2021. J Prev Alzheimers Dis. 2021;8:371-386.
8. Alzheimer’s Association. 2023 Alzheimer’s disease facts and figures. Alzheimers Dement. 2023;19(4):1598-1695 
9. Wessels AM, Dennehy EB, Dowsett SA, et al. Meaningful clinical changes in Alzheimer disease measured with the iADRS and illustrated using the donanemab TRAILBLAZER-ALZ study findings. Neurol Clin Pract. 2023;13(2):e200127. doi:10.1212/CPJ.0000000000200127
10. Bucci M, Chiotis K, Nordberg A; Alzheimer’s Disease Neuroimaging Initiative. Alzheimer’s disease profiled by fluid and imaging markers: tau PET best predicts cognitive decline. Mol Psychiatry. 2021 Oct;26(10):5888-5898. doi: 10.1038/s41380-021-01263-2.
11. Boccalini C, Ribaldi F, Hristovska I, Arnone A, Peretti DE, Mu L, Scheffler M, Perani D, Frisoni GB, Garibotto V. The impact of tau deposition and hypometabolism on cognitive impairment and longitudinal cognitive decline. Alzheimers Dement. 2023 Aug 9. doi: 10.1002/alz.13355.
12. Data on File. Lilly USA, LLC. DOF-DN-US-0053.
13. Data on File. Lilly USA, LLC. DOF-DN-US-0055.
14. Data on File. Lilly USA, LLC. DOF-DN-US-0029. 
15. Naber J. Alzheimer’s disease: An analysis of the diagnosed population and out-of-pocket cost exposure. Milliman Brief. February 2024.