FDA Approves Donanemab for Early Alzheimer Disease

The FDA granted approval for donanemab-azbt for the treatment of adults with early symptomatic Alzheimer disease.¹

The novel agent, which will be marketed as Kisunla, was developed by Eli Lilly and Company and is the first and only amyloid plaque-targeting therapy approved for early Alzheimer disease.

Amyloid is a naturally occurring protein in the body that can aggregate to form amyloid plaques. Excessive accumulation of these plaques in the brain is linked to memory and cognitive problems seen in Alzheimer disease. Donanemab aids in clearing these amyloid plaques, potentially slowing the decline that impairs abilities such as remembering new information, important dates, and appointments; planning and organizing tasks; preparing meals; using household appliances; managing finances; and maintaining independence.

According to the Alzheimer's Association, about 6.9 million (1 in 9) Americans 65 years and older have received a diagnosis of Alzheimer disease, 73% of whom are 75 years or older.² Almost two-thirds of patients with Alzheimer are women, and Black Americans are twice as likely to develop Alzheimer disease or other dementias at some point in their lives compared with White Americans. The organization predicts that Alzheimer disease prevalence among people in the US will grow to 12.7 million by 2050.

“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…. Each year, more and more people are at risk for this disease, and we are determined to make life better for them," said Anne White, executive vice president and president of Lilly Neuroscience, Eli Lilly and Company.¹

The approval was based on a comprehensive data package, including phase 3 results that were published in JAMA.³ In the multicenter, randomized, double-blind, placebo-controlled phase 3 trial (NCT04437511) spanning from June 2020 to November 2021, researchers evaluated the efficacy and safety of donanemab in 1736 participants with early symptomatic Alzheimer disease. Participants received either donanemab or placebo intravenously every 4 weeks for 72 weeks. Primary outcomes were assessed using the integrated Alzheimer Disease Rating Scale (iADRS) and Clinical Dementia Rating Scale (CDR-SB).

Results showed statistically significant improvements in multiple outcomes, including a reduction in iADRS score change at 76 weeks (−6.02 with donanemab vs −9.27 with placebo; P < .001) and CDR-SB score change (1.20 with donanemab vs 1.88 with placebo; P < .001) in the low/medium tau pathology population. Similar benefits were observed in the combined population of low/medium and high tau pathology. However, adverse events such as amyloid-related imaging abnormalities and infusion-related reactions were more frequent with donanemab.

The researchers concluded that donanemab demonstrated significant efficacy in slowing clinical progression among participants with early symptomatic Alzheimer disease and amyloid and tau pathology, highlighting its potential as a treatment option in this challenging disease context.

Previously, in January 2023, the FDA declined to give accelerated approval of donanemab in a complete response letter.⁴ In the letter, the agency requested additional data from at least 100 patients who had undergone a full year of treatment with donanemab, noting no other deficiencies.

In March 2024, the FDA pushed back its Q1 2024 approval deadline for the product, with Lilly reporting that the FDA planned to call a last-minute meeting of its outside advisors to review donenemab’s safety and efficacy data.⁵

The news comes after Biogen discontinued aducanumab after the drug's controversial accelerated approval in January 2023 for the treatment of Alzheimer disease.⁶ The drug was heralded as the first medicine shown to reduce disease progression and the first drug approval for Alzheimer disease in 2 decades; however, the FDA's decision drew staunch criticism from patient and provider communities over the quality of Biogen's data.⁷

The approval of donanemab could restore hope around the future of Alzheimer disease treatment.

"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," Howard Fillit, MD, cofounder and chief science officer at the Alzheimer's Drug Discovery Foundation, said in Lilly's statement on the approval.¹ "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."

References

1. Lilly's Kisunla (donanemab-azbt) approved by the FDA for the treatment of early symptomatic Alzheimer's disease. News release. Eli Lilly and Company; 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. Alzheimer’s disease facts and figures. Alzheimer’s Association. Accessed July 2, 2024. https://www.alz.org/alzheimers-dementia/facts-figures#:~:text=Nearly%207%20million%20Americans%20have,older%20(10.9%25)%20has%20Alzheimer's

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. FDA declines to give accelerated approval of donanemab in early symptomatic Alzheimer disease. AJMC^®. January 20, 2023. Accessed July 2, 2024. https://www.ajmc.com/view/fda-declines-to-give-accelerated-approval-of-donanemab-in-early-symptomatic-alzheimer-disease

5. What we’re reading: FDA delays decision on donanemab; weight loss drug costs; effective RSV treatment. AJMC. March 8, 2024. Accessed July 2, 2024. https://www.ajmc.com/view/what-we-re-reading-fda-delays-decision-on-donanemab-weight-loss-drug-costs-effective-rsv-treatment

6. Joszt L. Biogen abandons aducanumab, pivots focus to lecanemab for Alzheimer disease. AJMC. January 31, 2024. Accessed July 2, 2024. https://www.ajmc.com/view/biogen-abandons-aducanumab-pivots-focus-to-lecanemab-for-alzheimer-disease

7. Melillo G. How Biogen’s Aduhelm approval marks a precipitous turning point for the FDA. AJMC. July 14, 2021. Accessed July 2, 2024. https://www.ajmc.com/view/how-biogen-s-aduhelm-approval-marks-a-precipitous-turning-point-for-the-fda