LEQEMBI™ Alzheimer's Disease Monoclonal Antibody Clinical Trials, Efficacy, Indication, Side Effects
LEQEMBI™ (lecanemab-irmb) is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody (mAb) directed against aggregated soluble ("protofibril")* and insoluble forms of amyloid beta (Aβ) for the treatment of Alzheimer's disease (AD). LEQEMBI is not an AD vaccine but is a mAb infusion therapeutic. Treatment with LEQEMBI should only be initiated in patients with mild cognitive impairment or mild dementia stage of disease and confirmed presence of Aβ pathology. After the first infusion, 38% of LEQEMBI-treated patients had transiently decreased lymphocyte counts to <0.9 x109/L compared to 2% on placebo, and 22% of LEQEMBI-treated patients had transiently increased neutrophil counts to >7.9 x109/L compared to 1% on placebo.
On October 25, 2023, Eisai presented LEQEMBI® Interim Study Results and Clinical Improvement Data - Investigational Subcutaneous Formulation Clears 14% More Plaque Than IV, Pharmacokinetics (AUC) 11% Higher, And Similar ARIA Rates To IV; 76% Of Patients Showed No Decline And 60% Showed Clinical Improvement At 18 Months in Low-Tau Subpopulation in Additional Analysis of Clarity AD; Dual-Acting LEQEMBI Supports Brain Neuron Function by Removing Highly Toxic Proteins (Protofibrils) That Can Continue to Cause Neuronal Injury and Death Even After Plaque Removal, Offering Early AD Patients the Opportunity for Continued Benefit.
LEQEMBI was granted Accelerated Approval Pathway (BAN2401) on January 7, 2023, by the U.S. Food and Drug Administration (FDA). The FDA accepted Eisai's supplemental Biologics License Application (sBLA) on March 6, 2023, for LEQEMBI™ 100 mg/mL injection for intravenous use, supporting the conversion of the accelerated approval of LEQEMBI to a traditional approval. In addition, the LEQEMBI application has been granted Priority Review with a Prescription Drug User Fee and as Fast Track, Priority Review, and Breakthrough Therapy designations. The FDA's Advisory Committee discussed the 761269/s-001 application on June 9, 2023. FDA's PERIPHERAL AND CENTRAL NERVOUS SYSTEM DRUGS ADVISORY COMMITTEE MEETING BRIEFING DOCUMENT - LEQEMBI® (lecanemab-irmb). The FDA converted Leqembi to traditional approval on July 6, 2023. On June 10, 2024, the company announced that the FDA had accepted Eisai's sBLA for less frequent monthly lecanemab-irmb intravenous maintenance dosing. A Prescription Drug User Fee Act action date is January 25, 2025. Additionally, Eisai initiated the rolling submission of a BLA to the FDA for the Leqembi subcutaneous autoinjector for weekly maintenance dosing after the FDA granted it Fast Track designation in May 2024.
Eisai and Biogen have collaborated on the joint development and commercialization of AD treatments since 2014. Eisai leads lecanemab development and regulatory submissions globally, with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority. BioArctic has the right to commercialize lecanemab in the Nordic region, pending European approval, and Eisai and BioArctic are currently preparing for joint commercialization in the area.
LEQEMBI Availability 2024
On September 25, 2023, BioArctic AB's Eisai announced that LEQEMBI® Intravenous Infusion" (200 mg, 500mg, lecanemab) was approved in Japan. LEQEMBI is now approved in the UAE, U.S., China, and Israel., and applications have been submitted for review in the European Union, Australia, Brazil, Canada, Hong Kong, Great Britain, India, Russia, Saudi Arabia, South Korea, Taiwan, Singapore, and Switzerland.
LEQEMBI Indication
The U.S. FDA-approved LEQEMBI for people living with AD. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of the disease. Providers should obtain a recent brain MRI before starting treatment. There are no safety or effectiveness data on initiating treatment at earlier or later stages of AD than were studied. This indication is approved under accelerated approval based on a reduction in AB plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
According to the Alzheimer's Association's 2022 Alzheimer's Disease Facts and Figures, an estimated 6.5 million Americans aged 65 and older live with dementia due to AD. LEQEMBI is indicated for the treatment of Alzheimer's disease. Eisai estimates that there are 17 million patients with MCI or mild dementia due to AD in China.
LEQEMBI Dosage
The recommended dosage of LEQEMBI is 10 mg/kg, administered intravenously once every two weeks to eligible patients with confirmed presence of Aβ pathology before initiating treatment. Each solution contains 100 mg of lecanemab-irmb and arginine hydrochloride, histidine, histidine hydrochloride monohydrate, polysorbate 80, and water for Injection at an approximate pH of 5.0. In addition, Eisai continues to pursue a less frequent maintenance dosing regimen for LEQEMBI.
LEQEMBI Side Effects
On April 13, 2023, a case report that Science obtained showed a patient's history and autopsy "strongly suggests that lecanemab infusions were a catalyst leading to the events resulting in her death," says Vanderbilt University pathologist Hannah Harmsen.
LEQEMBI Price
Leqembi will cost about $20,438 per patient per year in Japan, based on a December 2023 ruling by a Japanese health ministry panel. On July 6, 2023, CMS.gov announced that broader Medicare coverage is now available for Leqembi (the brand name for lecanemab). Eisai Co., Ltd. announced on March 13, 2023, that the U.S. Veterans' Health Administration is providing coverage of LEQEMBI to veterans living with early stages of AD. Actual annualized pricing may vary by patient in the U.S.
LEQEMBI News
July 12, 2024 - Leqembi's approval in Israel is based on the large global Phase 3 Clarity AD study. In the Clarity AD study, Leqembi met its primary endpoint and all key secondary endpoints with statistically significant results.
May 14, 2024 - Eisai initiated the rolling submission of a Biologics License Application to the U.S. FDA for lecanemab-irmb (LEQEMBI®) subcutaneous autoinjector for weekly maintenance dosing.
January 9, 2024 - BioArctic AB's partner, Eisai, announced that Leqembi® was approved in China.
October 25, 2023 - Eisai Co., Ltd. and Biogen Inc. announced that Eisai presented new data for LEQEMBI® (lecanemab-irmb) 100 mg/mL injection for intravenous use in the Late Breaking Symposium 4 "Lecanemab for Early Alzheimer's Disease: Long-Term Outcomes, Predictive Biomarkers, and Novel Subcutaneous Administration."
July 6, 2023 - Eisai Co., Ltd. announced that the U.S. FDA had approved the sBLA supporting the traditional approval of LEQEMBI® 100 mg/mL injection for intravenous use, making LEQEMBI the first and only approved treatment shown to reduce the rate of disease progression and to slow cognitive and functional decline in adults with AD.
March 13, 2023 - Biogen welcomes the U.S. Veterans Health Administration's decision to provide coverage of LEQEMBI for veterans living with early stages of Alzheimer's disease.
March 5, 2023 - Eisai Co., Ltd. and Biogen Inc. announced today that the U.S. FDA accepted Eisai's supplemental Biologics License Application for LEQEMBI™ 100 mg/mL injection for intravenous use, supporting the conversion of the accelerated approval of LEQEMBI to a traditional approval.
January 6, 2023 - Based on the human health care concept, Eisai Co., Ltd. published its product pricing.
January 5, 2023 - The NEJM published a CONCLUSIONS: Lecanemab use in early Alzheimer's disease resulted in moderately less decline in measures of cognition and function than placebo at 18 months but was associated with adverse events. Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer's disease and are funded by Eisai and Biogen.
LEQEMBI Clinical Trials
Leqembi's approval in China in 2024 was based on the extensive global Phase 3 Clarity AD study. In the Clarity AD study, Leqembi met its primary and key secondary endpoints with statistically significant results. In November 2022, the results of the Clarity AD study were published in the New England Journal of Medicine journal.
In Eisai's confirmatory Clarity AD study, lecanemab demonstrated the consistency of results across scales of cognition and function and subgroups (race, ethnicity, comorbidities). Lecanemab treatment showed a 31% lower risk of converting to the next stage of disease by Global CDR assessment (Hazard Ratio: 0.69). A slope analysis using CDR-SB based on observed data and extrapolation to 30 months showed that lecanemab takes 25.5 months to reach the same level as the placebo at 18 months, indicating a 7.5-month slowing of progression. Modeling simulations based on the phase 2 trial data suggest that lecanemab may slow the rate of disease progression by 2.5-3.1 years and has the potential to help people remain in the earlier stages of AD for a more extended period. In addition, it was shown to maintain the health-related quality of life and reduce the burden on caregivers (23-56% reduction in score worsening). The convergence of evidence across cognition and function, disease progression, health-related quality of life, and caregivers demonstrates that lecanemab treatment may benefit patients, their care partners, physicians, and society.
On January 5, 2023, the NEJM published an ORIGINAL ARTICLE - Lecanemab in Early Alzheimer's Disease - that Lecanemab reduced markers of amyloid in early AD and resulted in moderately less decline in measures of cognition and function than placebo at 18 months but was associated with adverse events in phase 3 clinical trial. Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer's disease.
