Eiasi's approach to US pricing for Leqembi, a treatment for early Alzheimer's disease.

We consider a holistic approach in assessing value and making decisions that may affect patient access, so that our Leqembi pricing approach can maximize value for all stakeholders (patients, families, caregivers, healthcare providers, payers, employees and shareholders. According to a report from the Alzheimer's Association, "Changing the Trajectory of Alzheimer's Disease: How a Treatment by 2025 Saves Lives and Dollars", the total costs of care in the U.S. from all payers (i.e., Medicare, Medicaid, out-of-pocket and other payers), would increase from $267 billion in 2020 to $451 billion in 2030 if no treatment exists to delay the disease.

Social Impact of AD in the U.S: A recent 2022 study, "Projecting the Long-term Societal Values of Disease-Modifying Treatment for Alzheimer's Disease in the United States", quoted as many as 10 to 14 million Americans living with MCI (Mild Cognitive Impairment) of any etiology, the very mild symptomatic stage before onset of dementia stages, in which 55% have AD as the underlying pathology. In this study, the lifetime value of a disease-modifying treatment in Early AD (MCI due to AD and mild dementia stage of AD) from a U.S. societal perspective assuming a treatment effect of 30% relative decline in progression rates from MCI to mild dementia and from mild to moderate dementia was estimated at $134,418 per person.

Value of Leqembi Adoption to U.S. Society; Leqembi is indicated for the treatment of AD, and treatment with Leqembi should be initiated in patients with MCI or mild dementia stage of AD after confirmation of amyloid beta pathology (Early AD). In the U.S., we estimate that the diagnosed eligible Early AD population will reach approximately 100,000 individuals by year 3 representing a measured initial attainment in the real world and will increase gradually over the mid-to-long term given the time required to advance new screening and diagnostic technologies such as blood-based biomarkers to confirm amyloid beta pathology.

Published findings in a peer-reviewed journal(van Dyck. C, et al) from the confirmatory Phase III Clarity AD study in patients with Early AD demonstrate that Leqembi treatment resulted in less decline on measures of cognition and function than placebo at 18 months (27% slowing over 18 months measured by CDR-SB) and was associated with adverse events that were within expectation. Clarity AD results were consistent with that from the Phase II trial (Study 201) that was the basis for the FDA's accelerated approval and has been submitted to the FDA for review for traditional approval.

Leqembi's clinical data show that it could help patients maintain cognition, preserve activities of daily living and maintain functional ability for longer, and therefore, Leqembi's clinical efficacy could potentially translate into impactful outcomes for these patients and their families.

A simulation study using an established, validated disease model called Alzheimer’s disease Archimedes condition event (AD ACE), which is an individual patient-level model with a focus on predicting the trajectory of cognitive decline and simulating the effects of early interventions in AD, helped assess the potential lifetime value and economic impact of Leqembi in patients with Early AD based on clinical trial populations and findings. The results of this simulation study based on Study 201 of Leqembi were published in a peer-reviewed journal, and the model has been recently updated with data from the Clarity AD trial showing consistent outputs.

Per Patient Societal Value of Leqembi at $37,600 per Year in the U.S. by AD ACE Model; In the updated AD ACE simulation study using Clarity AD data, Leqembi treatment was projected to delay disease progression, resulting in an increase in patient's expected time in Early AD while reducing the time in more advanced severe states. Slowing of clinical decline in patients treated with Leqembi is estimated to delay disease progression by nearly 3 years on average (delay progression mainly from MCI to mild AD and from mild to moderate AD) compared to standard-of-care (SOC). Leqembi's impact on the disease trajectory is then modeled into an annual per-patient value to the U.S. society based on four components according to the following equation: a) quality-adjusted life-years (QALY) gains compared to SOC; b) willingness-to-pay (WTP) threshold; c) cost offsets compared to SOC; and d) time on treatment, all in present value term. Note that the costs, benefits and time on treatment need to be adjusted for the values between present time and future times using discounting in a health economic evaluation. Annual per patient value = (QALY gained ×WTP threshold)+ Cost offsets)/Time on treatment.

With regard to a) QALY gains, since health is a function of length of life and quality of life, this measure combines both attributes into one single index, with one QALY gain representing one additional year of a person's life at perfect health. Leqembi treatment was predicted to offer an additional 0.64 QALYs compared to SOC for an Early AD patient over lifetime by improving outcomes for both the patient and caregiver. With regard to b) WTP threshold per QALY gained, conventionally, the WTP threshold is based on 1 to 3 times country's per capita gross domestic product (GDP). In the U.S., as a result, a WTP threshold of $50,000 to $150,000 is referenced as the cost-effectiveness threshold, but a higher WTP threshold is often considered to account for the gravity of conditions with greater burden, and interventions that exhibit wider societal benefits, such as AD with substantial impacts on caregivers. A modified societal perspective at $200,000 WTP threshold per QALY gained is used in the U.S. when societal cost of the disease is large such as AD. With regard to c) cost offsets, avoidance of both direct medical/non-medical costs for AD management, as well as indirect costs of caregivers including family members totaling $7,415 over the lifetime for each Early AD patient, was predicted with Leqembi treatment compared to SOC. Direct costs contain cost of medications, medical visits, hospitalizations, living accommodations and community services for the patients. Indirect costs of caregivers, including family members, consider the monetary value for hours spent on caregiving activities. With regard to: d) time on treatment, Leqembi was modeled to be stopped upon transition to moderate AD dementia or worse. The average treatment duration in this Early AD population was estimated to be approximately 3.6 years with consideration of discounting to present value. Taking all four components together in present value term, for a) 0.64 QALYs gained b) at WTP threshold of $200,000 per QALY gained plus c) cost offsets of $7,415 over d) 3.6 years on treatment, the yearly per-patient value of Leqembi from a societal perspective was quantified at approximately $37,600. ($37,600=((0.64 ×$200,000) + $7,415)/3.6).

This yearly estimate of $37,600 equals to approximately $135,000 (0.64 × $200,000 + $7,415) in lifetime value per patient to the U.S. society. Over 10 years cumulatively, the gradual adoption of Leqembi treatment among Early AD patients could potentially generate positive social impact of several tens of billion dollars to the U.S. society, in the form of "clinical value" that help patients delay their disease progression, projected "social value" that help improve patients' and caregivers' quality of life and productivity, and simulated "economic value" that help reduce demand for health service.

Leqembi U.S. Launch Pricing at $26,500 per Year; While we estimate the per-patient-per-year value of Leqembi treatment to the U.S. society to be $37,600, Eisai decided to price Leqembi below 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) aiming to promote broader patient access, reduce overall financial burden, and support health system sustainability. 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 current biweekly regimen, upon significant amyloid beta clearance to prevent re-accumulation of amyloid beta biomarkers while maintaining clinical efficacy. This could further 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.

Patient Affordability; Eisai believes patient affordability must be a key consideration to promote patient access and intended use and benefits of Leqembi. Among the eligible Early AD patient population in the U.S., once the patient's insurer covers Leqembi, we estimate that approximately 91% of individuals will be covered by Medicare with Medigap (supplemental insurance), Medicare Advantage (Medicare-approved plans from private companies with potential supplemental coverage), Medicaid, and Commercial (private insurance). For these patients, their out-of-pocket costs for Leqembi treatment could range from $0 to a few dollars per day. Remaining 9% of the individuals will fall into the category of Medicare without supplemental insurance, and hence will be responsible for 20% of the Leqembi cost as co-insurance under Medicare Part B. For these patients, their estimated out-of-pocket costs for Leqembi at the price of $26,500 per year will translate into about $14.50 per day. Across the entire eligible Early AD patient population, we estimate the weighted average out-of-pocket costs for Leqembi to be about $2 per day.