LEQEMBI™ Alzheimer's Disease March 2023
LEQEMBI™ (lecanemab-irmb) is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody (mAbs) directed against aggregated soluble ("protofibril")* and insoluble forms of amyloid beta (Aβ) for the treatment of Alzheimer's disease (AD). 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.
LEQEMBI is not a vaccine but is a mAbs-administered infusion therapeutic. 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.
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 Act action date of July 6, 2023. The FDA is planning to hold an Advisory Committee to discuss this application but has not publicly announced the meeting date.
The FDA approved using LEQEMBI under the Accelerated Approval Pathway on January 7, 2023. The development code: BAN2401. The FDA granted this application Fast Track, Priority Review, and Breakthrough Therapy designations. And it was designated for Priority Review by the National Medical Products Administration in China on February 27, 2023. In addition, 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.
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.
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.
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.
Based on the human health care concept, Eisai is committed to improving patients' health outcomes and quality of life, simplifying care delivery, increasing health system efficiency, and spurring future investments in AD. This approach includes clinical outcome assessments of our medicines and the benefits we deliver to patients, their families, and caregivers as the "clinical value" and the projected "social value" that helps improve patients' and caregivers' quality of life and productivity.
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.
In addition, Eisai continues to pursue a less frequent maintenance dosing regimen for LEQEMBI, such as monthly instead of the current biweekly regimen, upon significant amyloid beta clearance to prevent re-accumulation of amyloid beta biomarkers while maintaining clinical efficacy. This could lower the yearly cost of LEQEMBI during the maintenance dosing phase, for example, from $26,500 to potentially about half of this figure, given less amount of drugs.
LEQEMBI News 2023
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 reduced markers of amyloid in early Alzheimer's disease and 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 Eisai's large 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 caregiver burden demonstrate that lecanemab treatment may benefit patients, their care partners, physicians, and society.