A new drug for people with Alzheimer's disease. Results of a two-year study presented.
- On July 30, Eisai Co., Ltd. and Biogen Inc. announced that results from a two-year real-world clinical trial conducted in the United States with lecanemab, an antibody directed against amyloid beta (Aβ) protofibrils, were presented at this year's Alzheimer's Association International Conference (AAIC), held in Toronto, Canada, and remotely.
- Only lekanemab addresses the cause of Alzheimer's disease in two ways - by acting in a targeted manner on both amyloid plaques and protofibrils, which may also affect the processes occurring in the tau protein pathway
- In July 2023, lekanemab was approved for marketing in the United States under the standard procedure for the treatment of early-stage Alzheimer's disease.
- This retrospective study was conducted to evaluate lecanemab therapy in a real-world clinical setting at 15 medical centers in the United States, and the final report is expected to be published at the end of the third quarter of Eisai's fiscal year ending March 31, 2026. This presentation represents an interim report as of July 1, 2025.
In an interim analysis, information was collected from 178 individuals with early-onset Alzheimer's disease from nine medical centers in the United States using a standardized case report form. Patients had mild cognitive impairment (MCI) due to Alzheimer's disease at baseline, 57.6%, and mild Alzheimer's disease (42.4%). The mean age of the patients was 74.2 (±6.6) years, with a male-to-female ratio of 44.6 to 55.4.
The mean duration of lecanemab treatment was 375.4 days (± 182.8 days). The mean time from diagnosis to first treatment was 224.2 days (± 295.4 days), and the mean number of lecanemab treatment administrations was 24.8 (± 11.5). At the time of reporting, 87.4% of patients (152 patients) continued treatment with lecanemab. Adverse reactions leading to treatment discontinuation included ARIA-E (ARIA-edema/effusion) in two patients (1.1%), ARIA-H (ARIA-cerebral microhemorrhages, cerebral hemorrhage, and superficial hemosiderin deposits) in two patients (1.1%), and concomitant ARIA-E and ARIA-H in one patient (0.6%). Three patients (1.7%) discontinued treatment due to adverse events other than ARIA. Additionally, 11 patients (6.3%) reported that they discontinued treatment for personal reasons or on the advice of a physician or their own decision.
In this study, 83.6% of patients remained in the same clinical stage or improved from mild dementia to MCI (stable: 76.9%, improved: 6.7%). Furthermore, at the time of the interim data release, 86.7% of patients who received at least 40 doses over 18 months remained in a stable condition or showed clinical improvement (stable: 66.7%, improved: 20.0%).
Among 178 patients, ARIA was observed in 23 (12.9%). ARIA-E was observed in 14 (7.9%), of whom 12 (6.7%) were asymptomatic. ARIA-H occurred in 11 patients (6.2%), all asymptomatic. Infusion-related reactions occurred in four patients (2.2%). In addition, no serious bleeding events or deaths were reported.
Of the 178 patients included in the study, 12 were excluded due to unknown status. Of the remaining 166 patients, 30 (18.1%) were APOE ε4 homozygotes, 84 (49.4%) were heterozygotes, and 54 (32.5%) were negative for the apolipoprotein E ε4 (ApoE ε4) gene. Generally, the homozygote rate among individuals with Alzheimer's disease is considered to be at least 15%.
The incidence of ARIA was 20.0%, 9.8%, and 14.8% in homozygous carriers, heterozygous carriers, and non-carriers, respectively (45.0%, 19.0%, and 13.0%, respectively, in the 18-month Clarity AD Phase 3 pivotal study). The incidence of ARIA-E and ARIA-H was 13.3% and 10.0%, respectively (32.6% and 39.0% in the Clarity AD homozygote cohort), which is within the range approved by the FDA. Most ARIA cases were asymptomatic. The incidence of adverse events leading to treatment discontinuation was 16.7% in homozygotes, 2.4% in heterozygotes, and 5.6% in non-carriers.
In 73.3% of homozygous patients, clinical status remained stable or improved (stable: 66.6%, improved: 6.7%), 88.0% of heterozygous patients remained stable or improved (stable: 83.0%, improved: 4.9%), and in 85.2% of non-carrier patients, clinical status remained stable or improved (stable: 75.9%, improved: 9.3%).
In Alzheimer's disease, blood-based biomarkers (BBMs) are being developed to identify Aβ pathological changes in the brain, with the intention of using them in screening (triage) and for confirmatory diagnosis. Of the 178 study participants, BBM diagnosis was performed in 49 patients (27.5%). In some cases (11 patients, 6.1%), they were also used for confirmatory diagnosis. Data collected from clinical practice showed that the number of BBM tests doubled every 4–8 months, with the fastest increase in the number of BBM tests using the p-tau217 biomarker.
Results of a survey on physician, patient, and caregiver satisfaction with lecanemab therapy are presented. The survey was conducted using questionnaires and interviews with nine US physicians and assessed the treatment from multiple perspectives, including its efficacy, safety, and impact on quality of life (QOL).
According to physicians, the average level of satisfaction with the effectiveness and safety of treatment (on a scale of up to 10 points) was 8.7. The assessment criteria included: cognitive function – 8.1, daily functioning – 8.1, behavioral/neuropsychiatric symptoms – 7.9, and QOL – 8.0. The level of patient satisfaction assessed by physicians was 8.8, and the level of caregiver satisfaction – 8.2. These results indicate a positive assessment of the effectiveness and safety of lekanemab in real-world clinical practice and confirm its therapeutic value.
Attention:
Retrospective studies conducted in real-world settings can be very valuable, providing additional information to complement clinical trial data. However, they have a number of limitations:
- Possibility of systematic errors
- Data completeness and consistencyBecause data are collected from different patient profiles at independent centers, they may be collected inconsistently.
Data inconsistency is eliminated by providing centers with access to standard electronic case report forms.
- Lack of a control groupInterpretation of the data may be limited because real-world studies do not use placebo control groups.
- Confounding factorsThere is no way to control for confounding factors that may affect the relationship between product exposure and treatment outcome.
Eisai leads the development and global regulatory submission process for lecanemab, with Eisai and Biogen jointly marketing the product and Eisai having final decision-making authority.
Protofibrils are believed to be the most toxic form of Aβ, contributing to the brain damage seen in Alzheimer's disease, and they play a significant role in cognitive decline in this progressive, devastating disease. Protofibrils can cause damage to neurons and synapses in the brain, which in turn can negatively impact cognitive function through multiple mechanisms.1 The mechanism by which this damage occurs has been described to involve not only increased development of insoluble Aβ plaques but also greater direct impairment of signaling between neurons and other cells. It is thought that reducing protofibrils may reduce brain neuronal damage and cognitive dysfunction, potentially preventing the progression of AD.
Lekanemab is the result of a strategic research collaboration between Eisai and BioArctic. It is a humanized immunoglobulin gamma (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). Protofibrils are believed to contribute to the brain damage seen in Alzheimer's disease and are considered the most toxic form of Aβ, playing a major role in cognitive decline in this progressive, devastating disease.
Protofibrils cause damage to neurons in the brain, which in turn can negatively impact cognitive function through multiple mechanisms, not only by increasing the development of insoluble Aβ plaques but also by increasing direct damage to neuronal cell membranes and the connections that transmit signals between nerve cells or nerve cells and other cells.
It is believed that reducing protofibrils may slow the progression of Alzheimer's disease by reducing damage to neurons in the brain and lowering cognitive dysfunction.
Lekanemab has been approved in 46 countries and is currently under regulatory review in 10 countries. In January 2025, a supplemental biologics license application (BLA) for intravenous maintenance therapy with lekanemab was approved in the United States. After an 18-month initial phase with once-every-two-week dosing, a transition to a maintenance dosing regimen of 10 mg/month every four weeks or continuation at 10 mg/month once every two weeks can be considered. Additionally, in January 2025, the U.S. Food and Drug Administration (FDA) accepted Eisai's Biologics License Application (BLA) for weekly maintenance therapy with lekanemab as a subcutaneous injection (auto-injector). The FDA set a decision deadline of August 31, 2025, under the Prescription Drug User Fee Act (PDUFA).
A Phase 3 clinical trial (AHEAD 3-45) has been underway since July 2020 in people with preclinical Alzheimer's disease, meaning they are clinically healthy and have intermediate or elevated levels of amyloid in their brains. The AHEAD 3-45 trial is being conducted through a public-private partnership between the Alzheimer's Clinical Trial Consortium, which provides infrastructure for academic clinical research in Alzheimer's disease and related dementias in the United States and is funded by the National Institute on Aging, part of the National Institutes of Health, and Eisai and Biogen. Since January 2022, the Tau NexGen clinical trial for dominantly inherited Alzheimer's disease (DIAD) has been ongoing, led by the Dominantly Inherited Alzheimer's Disease Network Unit (DIAN-TU) led by Washington University School of Medicine in St. Louis, with lecanemab as the primary anti-amyloid therapy.
Eisai and Biogen have been collaborating on the development and commercialization of a treatment for Alzheimer's disease since 2014. Eisai leads the development and global regulatory submission of lecanemab, with both companies co-marketing the product and Eisai having final decision-making authority.
Eisai and BioArctic have had a long-term collaboration in the development and commercialization of treatments for Alzheimer's disease since 2005. Eisai obtained the global rights to research, develop, manufacture, and commercialize lecanemab for the treatment of Alzheimer's disease under an agreement with BioArctic in December 2007. In May 2015, an agreement was signed to support the development and commercialization of lecanemab.
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