Once-Monthly Dosing! New Therapy Approved by U.S. FDA Reduces Risk of Early Symptomatic Alzheimer's Disease Progression by 39%

1 hour agoMedical New Line NetworkPublished in Shanghai

In the TRAILBLAZER-ALZ 2 Phase III study, Kisunla showed the best results in patients at the earliest stage of disease progression.

On July 2, 2024, the U.S. Food and Drug Administration (FDA) approved Kisunla™ (donanemab-azbt, 350 mg/20 mL intravenous infusion once monthly), Eli Lilly and Company's (NYSE: LLY) Alzheimer's disease (AD) therapy for the treatment of adults with early symptomatic AD, including patients with mild cognitive impairment (MCI) and those with mild dementia-stage AD with confirmed amyloid pathology.¹^,2Kisunla is the first and only therapy with evidence to support stopping treatment after clearing amyloid plaques, which can reduce treatment costs and decrease the number of infusions.³^-6

"Kisunla is highly significant for patients with early-stage Alzheimer's disease, who are in urgent need of effective treatment options. We know that when people receive treatment early in the course of the disease, it can maximize the potential benefits of these drugs. We are working with other partners to improve the detection and diagnosis of Alzheimer's disease," said Anne White, Executive Vice President of Eli Lilly and Company and President of Lilly Neuroscience. "We sincerely thank the patients and their families who participated in our clinical programs, as well as the Lilly scientists and partners who have been conducting research for decades. Each year, more and more people face the risk of this disease, and we are committed to improving their lives."

Amyloid is a protein naturally produced by the body, which can clump together to form amyloid plaques. The excessive accumulation of amyloid plaques in the brain may lead to memory and thinking problems associated with Alzheimer's disease.⁷^,8Kisunla can help the body clear excessive accumulation of amyloid plaques and slow down the conditions that may lead to the inability to remember new information, important dates and meetings, plan management, cooking, using household appliances, managing finances, and the decline of independent self-care abilities.¹^{, 7-9}

In the TRAILBLAZER-ALZ 2 Phase III study, Kisunla showed the best effect in patients at the earliest stage of disease progression. During the 18-month trial period, participants were divided into two groups for analysis: one group with earlier disease progression (having low to moderate levels of tau protein) and the overall population, including subjects with low, moderate, and high tau levels.¹^,10,11Treatment with Kisunla significantly slowed clinical decline in both groups.¹In patients with earlier disease progression, those treated with Kisunla showed a 35% significant reduction in the rate of decline on the integrated Alzheimer's Disease Rating Scale (iADRS), which includes memory, thinking, and daily functioning, compared to placebo. According to the iADRS scale, in the overall population, drug treatment significantly slowed decline by 22%.^1,12In the two groups of subjects, those treated with Kisunla showed up to a 39% reduction in the risk of disease progression to the next clinical stage compared to those receiving a placebo.¹³

In the overall subject population, compared to the start of the study, Kisunla use reduced amyloid plaques by an average of 61% at 6 months, 80% at 12 months, and 84% at 18 months.¹^,14One therapeutic goal of the study is to reduce amyloid plaques to levels consistent with visually negative amyloid positron emission tomography (PET). If it is confirmed that a participant has reached this level, Kisunla treatment will be completed and switched to placebo for the remainder of the study.

Kisunla may cause imaging abnormalities associated with amyloid plaque-targeting therapies ("ARIA"), a potential side effect that usually does not cause symptoms. It can be detected through magnetic resonance imaging (MRI) scans and, when it occurs, may present as temporary swelling in areas of the brain, which typically resolves over time, or as small spots of bleeding within or on the surface of the brain. Occasionally, bleeding in larger areas of the brain may occur.¹^,2ARIA may be severe and have life-threatening effects. Kisunla may also cause certain types of allergic reactions, some of which may be severe and life-threatening, usually occurring during the infusion or within 30 minutes after the infusion. Headache is another common side effect. For more information, see the following.Indications and Safety Summary with Warnings。

"This approval marks another step forward in advancing the standard treatment for Alzheimer's patients, which will ultimately include a range of novel therapies, offering much-needed hope to the Alzheimer's community. As a physician, I am encouraged by the potential for a finite course of treatment that may reduce out-of-pocket costs and infusion burdens for eligible patients," said Howard Fillit, M.D., Co-Founder and Chief Science Officer of the Alzheimer’s Drug Discovery Foundation (ADDF). "The ability to diagnose and treat Alzheimer's earlier than we currently can could significantly slow disease progression, buying patients precious time to remain independent longer."

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.

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On July 2, 2024, the U.S. Food and Drug Administration (FDA) approved Kisunla™ (donanemab-azbt, 350 mg/20 mL intravenous infusion once monthly), Eli Lilly and Company's (NYSE: LLY) Alzheimer's disease therapy for the treatment of adults with early symptomatic Alzheimer's disease (AD), including patients with mild cognitive impairment (MCI) and patients with mild dementia-stage AD with confirmed amyloid pathology.¹^,2Kisunla is the first and only therapy with evidence to support stopping treatment after clearing amyloid plaques, which can reduce treatment costs and decrease the number of infusions.³^-6

"Kisunla is highly significant for patients with early-stage Alzheimer's disease, who are in urgent need of effective treatments. We know that when people receive treatment early in the course of the disease, it can maximize the potential benefits of these drugs. We are working with other partners to improve the detection and diagnosis of Alzheimer's disease," said Anne White, Executive Vice President of Eli Lilly and Company and President of Lilly Neuroscience. "We sincerely thank the patients and their families who participated in our clinical programs, as well as the Lilly scientists and partners who have conducted research for decades. Each year, more and more people face the risk of this disease, and we are committed to improving their lives."

Amyloid is a protein naturally produced by the body that can clump together to form amyloid plaques. Excessive accumulation of amyloid plaques in the brain may lead to memory and thinking problems associated with Alzheimer's disease.⁷^,8Kisunla can help the body clear excessive accumulation of amyloid plaques and slow down the conditions that may lead to people being unable to remember new information, important dates and meetings, plan management, cooking, using household appliances, managing finances, and the decline of independent self-care abilities.¹^{, 7-9}

In the TRAILBLAZER-ALZ 2 Phase III study, Kisunla showed the best results in patients at the earliest stage of disease progression. Over the 18-month trial period, participants were divided into two groups for analysis: one group with earlier disease progression (having low to moderate levels of tau protein) and the overall population, including subjects with low, moderate, and high tau levels.¹^,10,11Treatment with Kisunla significantly slowed clinical decline in both groups.¹In patients with earlier disease progression, those treated with Kisunla showed a 35% significant reduction in the rate of decline on the integrated Alzheimer's Disease Rating Scale (iADRS), which includes memory, thinking, and daily functioning, compared to placebo. According to the iADRS scale, in the overall population, the drug treatment significantly slowed decline by 22%.^1,12Among the two groups of subjects, those treated with Kisunla showed up to a 39% reduction in the risk of disease progression to the next clinical stage compared to those receiving a placebo.¹³

In the overall subject population, compared to the start of the study, the use of Kisunla reduced amyloid plaques by an average of 61% after 6 months, 80% after 12 months, and 84% after 18 months.¹^,14One therapeutic goal of the study is to reduce amyloid plaques to levels consistent with visually negative amyloid positron emission tomography (PET). If it is confirmed that a participant has reached this level, Kisunla treatment will be completed and switched to placebo for the remainder of the study.

Kisunla may cause imaging abnormalities associated with amyloid plaque-targeting therapies (or "ARIA"), a potential side effect that usually does not cause symptoms. It can be detected through magnetic resonance imaging (MRI) scans, and when it occurs, it may present as temporary swelling in areas of the brain, which typically resolves over time, or as small spots of bleeding within or on the surface of the brain. Occasionally, bleeding in larger areas of the brain may occur.¹^,2ARIA may be severe and have life-threatening effects. Kisunla may also cause certain types of allergic reactions, some of which may be severe and life-threatening, usually occurring during the infusion or within 30 minutes after the infusion. Headache is another common side effect. For more information, see the following.Indications and Safety Summary with Warnings。

"This approval marks another step forward in advancing the standard treatment for Alzheimer's patients, which will eventually include a range of novel therapies, providing much-needed hope for the Alzheimer’s community. As a physician, I am encouraged by the potential for treatment over a defined course, which may reduce out-of-pocket costs and infusion burdens for eligible patients," said Howard Fillit, M.D., Co-Founder and Chief Science Officer of the Alzheimer's Drug Discovery Foundation (ADDF). "The ability to diagnose and treat Alzheimer’s earlier than we currently do could significantly slow disease progression, buying patients precious time to remain independent longer."