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FDA approves Kisunla™ (donanemab-azbt) for Alzheimer’s disease

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On July 2, 2024, the U.S. Food and Drug Administration (FDA) approved Kisunla™ (donanemab-azbt, 350 mg/20 mL once-monthly injection for IV infusion) for adults with early symptomatic Alzheimer’s disease (AD) and people with the mild dementia stage of AD, with confirmed amyloid pathology. Donanemab (LY3002813) is a humanized IgG1k monoclonal antibody that targets Ab(p3-42), a pyroglutamate form of amyloid beta that is aggregated in amyloid plaques. Donanemab was granted Breakthrough Therapy designation by FDA for the treatment of AD.

FDA’s approval was based in part on results from the TRAILBLAZER-ALZ 2 Phase 3 study in which 1736 patients with early symptomatic AD with amyloid and low/medium or high tau pathology were randomized 1:1 to receive IV donanemab (n=860) or placebo (n=874) Q4W for 72 weeks. [1] 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. Treatment with Kisunla significantly slowed clinical decline in both groups, with people who were the least advanced in the disease experiencing the strongest results with Kisunla.

  1. Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J, Wessels AM, Shcherbinin S, Wang H, Monkul Nery ES, 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.

FDA approves Leqembi (lecanemab-irmb) for the treatment of Alzheimer’s disease

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On January 6, 2023, the U.S. Food and Drug Administration approved Leqembi (lecanemab-irmb) via the Accelerated Approval pathway for the treatment of Alzheimer’s disease. The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials. The approved dose of lecanemab is 10 milligram/kilogram every two weeks.

Lecanemab (BAN2401) is a humanized anti-amyloid beta protofibril IgG1k antibody initially developed by BioArctic Neuroscience. BAN2401 was licensed to Eisai in a collaboration agreement, allowing the jointly development of lecanemab as a treatment for Alzheimer disease (AD). Under an agreement with Biogen, Eisai and Biogen co-commercialize and co-promote lecanemab.

The accelerated approval was supported by data from Study 201 (NCT01767311), which assessed the clinical efficacy of lecanemab at multiple doses (2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, 10 mg/kg biweekly) or placebo and explored the dose response of lecanemab using a composite clinical score (ADCOMS) in 856 patients with mild cognitive impairment due to AD and mild AD with confirmed presence of amyloid pathology. Patients receiving the treatment had significant dose- and time-dependent reduction of amyloid beta plaque, with patients receiving the approved dose of lecanemab, 10 milligram/kilogram every two weeks, having a statistically significant reduction in brain amyloid plaque from baseline to Week 79 compared to the placebo arm, which had no reduction of amyloid beta plaque.

Lecanemab is also being evaluated in the Clarity AD Phase 3 study (NCT03887455), which is designed to evaluate the efficacy, long-term safety, and tolerability of 10 mg/kg IV lecanemab administered every 2 weeks in 1795 patients with early AD. The primary outcome measurement was the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months of treatment. In September 2022, Eisai Co and Biogen Inc announced positive topline results from Clarity AD Phase 3 trial where lecanemab met the primary endpoint by reducing by 27% the clinical decline on the CDR-SB compared with placebo at 18 months. All key secondary endpoints were also met. Based on results of the study, Eisai may file for traditional approval in the US and for marketing authorization applications in Japan and Europe.

Aduhelm (aducanumab) approved for the treatment of Alzheimer’s disease.

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On June 7, 2021, the U.S. Food and Drug Administration approved Aduhelm (aducanumab) for the treatment of Alzheimer’s disease. Developed by Biogen, aducanumab is a human IgG1 antibody that targets anti-amyloid b. Biogen licensed the worldwide rights to aducanumab from Neurimmune in 2007, and has collaborated with Eisai on the global development and commercialization of aducanumab since 2017.

The late-stage development program for Aduhelm consisted of two Phase 3 clinical trials. One study met the primary endpoint, showing reduction in clinical decline. The second trial did not meet the primary endpoint.  In all studies in which it was evaluated, Aduhelm reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion.  The reduction in amyloid  plaque is considered a surrogate for a reduction in clinical decline. Aduhelm was approved using FDA’s accelerated approval pathway, which can be based on the drug’s effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. A post-approval trial to verify that the drug provides the expected clinical benefit is required.

Need help keeping up to date on US and EU approvals?

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.