FDA Approves Donanemab-Azbt for Early Symptomatic Alzheimer Disease

Updated on July 2, 2024, at 4:40 pm to include Alzheimer’s Drug Discovery Foundation statement.

The FDA has approved donanemab-azbt (Kisunla; Eli Lilly and Company) for the treatment of early symptomatic Alzheimer disease, including individuals with mild cognitive impairment and those in the mild dementia stage of AD who have confirmed amyloid pathology. Donanemab-azbt is a once monthly intravenous infusion and is the first and only amyloid plaque targeting therapy that supports stopping therapy when the plaque is removed.¹

"This approval marks another step forward in evolving the standard of care for people living with Alzheimer disease that will ultimately include an arsenal of novel treatments, providing much needed hope to the Alzheimer 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," Howard Fillit, MD, co-founder and chief science officer at the Alzheimer's Drug Discovery Foundation (ADDF), said in a news release. "Diagnosing and treating Alzheimer sooner than we do today has the potential to meaningfully slow disease progression, giving patients invaluable time to maintain their independence for longer."¹

The approval is based on results from the TRAILBLAZER-ALZ 2 (NCT04437511) study, which found that the drug significantly slowed clinical progression at 76 weeks. The study results, published in JAMA, showed that of the 24 outcomes evaluated, 23 outcomes were statistically significant.²

The study was a phase 3, randomized, double-blinded, placebo-controlled trial that included 277 sites in 8 countries. There were 1736 individuals enrolled from June 19, 2020, to November 5, 2021. Individuals included were aged 60 to 85 years with early symptomatic Alzheimer disease, and treatment was randomized with either donanemab 700 mg for the first 3 doses followed by 1400 mg or the placebo. Both regimens were administered intravenously every 4 weeks for up to 72 weeks, according to the study authors.²

The primary end point included change in Integrated Alzheimer Disease Rating Scale score from baseline to 76 weeks in the low to medium tau population and the combined low to medium and high tau populations. In the low to medium tau population, 1182 individuals were included.²

For the primary outcome, the least-squares mean change from baseline for the low to medium population was –6.02 in the donanemab group compared with –9.27 for the placebo group, demonstrating an approximate 35.1% slowing of disease progression. In the combined population the change was –10.19 and –13.11, respectively, showing a 22.3% slowing of disease progression.²

The incidence of death was approximately 1.9% in the donanemab group and 1.1% in the placebo group. Further, the incidence of serious adverse events was 17.4% and 25.8%, respectively. For amyloid-related imaging abnormalities of edema/effusion, microhemorrhages, and hemosiderin deposits, events occurred in 26.8% and 14.9% of patients, respectively. Infusion related reactions were reported by 8.7% and 0.5% of individuals, respectively.²

About the Trial

Trial Name: A Study of Donanemab (LY3002813) in Participants With Early Alzheimer's Disease (TRAILBLAZER-ALZ 2)

ClinicalTrials.gov ID: NCT04437511

Sponsor: Eli Lilly and Company

Completion Date (Estimated): August 2025

The cost of treatment at 6 months, 12 months, and 18 months is expected to be approximately $12,522, $32,000, and $48,696, respectively. The total cost will be based on when patients complete treatment, especially because the FDA states that prescribers can stop the dosing of the drug based on removal of amyloid plaque levels. This has the potential to reduce out-of-pocket costs and require fewer transfusion compared to other therapies.¹

“More patients start out in an asymptomatic phase, and it's thought that they'll start to develop pathology in the brain accumulation of proteins normally 20 to 30 years before they start showing symptoms, which is why risk factor modification needs to start in midlife, so around our 50s, and then some patients will progress on to mild cognitive impairment,” Nicole Purcell, DO, MS, a neurologist and senior director of Clinical Practice at the Alzheimer’s Association said in a session at the Academy of Managed Care Pharmacy Nexus 2023 conference. “We have more work to do with making sure that the medications that are being approved are being evaluated in diverse populations that they're intended to serve.”³

In a statement from the ADDF, the approval of the drug is a breakthrough that moves the field closer to treating Alzheimer disease through combination therapy and precision medicine.⁴

“We are no longer asking whether or not we can diagnose Alzheimer, but, rather, how early can we detect the disease?” Fillit said in the statement. “With the validation of new biomarkers, especially blood tests, we can now diagnose the disease with ease and intervene earlier than ever, including in the preclinical phase, opening the door prevention. We can finally deliver the right drugs to the right patients at the right time.”⁴

According to the Foundation, the pipeline is saturated and ready to deliver medications in the next few years, with 75% of drugs focused on amyloid and tau targets. Advanced biomarkers can help to facilitate drug development, which the organization stated is evident with this drug, using AmyvidPET scan and PrecivityAD, a C2N blood test. The organization added that the TRAILBLAZER-ALZ 2 utilized drug development and biomarker development, which resulted in more efficient clinical trials.⁴

“This milestone will not only catalyze the next generation of therapies, but also reframe how we deliver treatments. It’s promising to see that some patients essentially enter remission, where they achieve full amyloid clearance with no resurgence in substantial plaque buildup for several years to follow," Fillit said in the statement.⁴

FDA Approves Donanemab-Azbt for Early Symptomatic Alzheimer Disease

About the Trial

References

1. Lilly's Kisunla (donanemab-azbt) approved by the FDA for the treatment of early symptomatic Alzheimer's disease. News release. Eli Lilly. July 2, 2024. Accessed July 2, 2024. https://investor.lilly.com/news-releases/news-release-details/lillys-kisunlatm-donanemab-azbt-approved-fda-treatment-early

2. 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

3. Gallagher A. Experts Highlight Need for Increased Screening for Dementia, Alzheimer Disease. Pharmacy Times. October 19, 2023. Accessed July 2, 2024. https://www.pharmacytimes.com/view/experts-highlight-need-for-increased-screening-for-dementia-alzheimer-disease

4. ADDF STATEMENT ON FDA’S TRADITIONAL APPROVAL OF KISUNLA (Donanemab). News release. Alzheimer’s Drug Discovery Foundation. July 2, 2024. Accessed July 2, 2024. Email.