LEQEMBI™ Alzheimer's Disease Therapy
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 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.
LEQEMBI was granted Accelerated Approval Pathway (BAN2401) on January 7, 2023. The U.S. Food and Drug Administration (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, following a determination that a confirmatory trial verified clinical benefit.
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.
LEQEMBI Indication
The FDA-approved LEQEMBI for people living with AD. 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. 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.
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 International
On September 25, 2023, BioArctic AB's Eisai announced that LEQEMBI® Intravenous Infusion" (200 mg, 500mg, lecanemab) has been approved in Japan as a treatment for slowing the progression of mild cognitive impairment and mild dementia due to AD. And it was designated for Priority Review by the National Medical Products Administration in China on February 27, 2023.
LEQEMBI Price
On July 6, 2023, CMS.gov announced 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.
While the company estimated the per-patient-per-year value of LEQEMBI treatment to the U.S. society to be $37,600, Eisai decided to price LEQEMBI below the quantified societal value at the wholesale acquisition cost (WAC) of $26,500 per year (estimated annual price based on 10mg/kg IV biweekly for average U.S. patient weight of 75kg based on Study 201 and Clarity AD). As such, the WAC for the 200mg vial is $254.81, and the WAC for the 500mg vial is $637.02. Actual annualized pricing may vary by patient.
On August 11, 2023, the AP reported insurers selling coverage in North Carolina, Pennsylvania, and New York, among other states, won't cover Leqembi with insurance offered on the individual market and through employers.
LEQEMBI News 2023
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. Funded by Eisai and Biogen.
November 30, 2022 - Eisai Co., Ltd. and Biogen Inc. announced that the results from Eisasizeablearge global Phase 3 confirmatory Clarity AD clinical study of lecanemab were presented at the 2022 Clinical Trials on Alzheimer's Disease conference and virtually.
LEQEMBI Clinical Trials
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.
