New Analysis of Phase 3 Clarity AD Study Highlights Health and Economic Benefits From Lecanemab

Ivan Cheung

Recently published data using an evidence-based model developed to simulate the effects of lecanemab (Leqembi; Eisai) suggested that lecanemab plus standard of care (SoC) would improve health and humanistic outcomes and reduce economic burden for patients and caregivers in early Alzheimer disease (AD).^1,2

Over a lifetime time horizon, patients treated with lecanemab plus SoC gained an additional 0.62 years of life vs SoC alone (6.23 years vs 5.61 years). The mean time on lecanemab was 3.91 years, and the treatment was associated with an increase in patient quality-adjusted life years (QALYs) of 0.64 when both patient and caregiver utilities were considered.

Published in Neurology and Therapy, the previously developed model used interconnected predictive equations based on longitudinal clinical and biomarker data derived from the Alzheimer’s Disease Neuroimaging Initiative. Led by Amir A. Tahami, adjunct professor of epidemiology and biostatistics, McGill University, this model was updated using data from the phase 3 Clarity AD trial (NCT03887455) and published literature to compare lecanemab plus SoC vs SoC alone both from the US payer and societal perspectives.

When excluding drug acquisition costs, the total costs per patient on a combination of these therapeutic approaches decreased by $6263 from a payer perspective and $7451 from a societal perspective relative to SoC alone. Additional monitoring and amyloid-related imaging abnormality (ARIA) management costs totaled $1018 and $68, respectively. Above all, the model estimated that the annual societal value of lecanemab for the US payer perspective was $18,709 to $35,678 for the willingness-to-pay (WTP) threshold of $100,000 to $200,000 per QALY gained, respectively.

"The outcomes of this simulation quantitatively demonstrate the societal value of lecanemab, showing that lecanemab provides significant impact not only to people living with early AD and their caregivers, but also to society as a whole. While a broader range of values was considered, the severity-adjusted WTP threshold of $200,000 per QALY gained accurately reflects the societal value of lecanemab," Ivan Cheung, senior vice president, and Global Alzheimer’s Disease Officer, Eisai, said in a statement.¹ "Eisai will continue to transparently and expeditiously publish data and information about lecanemab in order to transparently discuss its societal value for people and countries around the globe."

Investigators conducted several scenario analyses as well, one of which showed that patients without symptomatic drug use at baseline had higher QALYs gained (payer: 0.68 vs 0.61; societal: 0.71 vs 0.64) compared with the overall population, yielding higher value estimates (payer: $37,069 vs $35,678; societal: $39,345 vs $37,351). When applying the treatment effect stratified by apolipoprotein e4 (APOE4) gene carrier status, a greater at-risk group, the estimated value decreased by 6% for carriers and increased by 8% for noncarriers compared with the base-case.²

READ MORE: P-Tau217 Continues to Show Benefit as Predictor of Cognitive Decline in Preclinical Alzheimer Disease

When dividing patients based on their baseline cerebrospinal fluid t-tau level, lecanemab produced better outcomes and a higher value in those with lower T-tau at baseline. The value changed from 25% to –19% and 29% to –22% from the lowest to highest quintile vs the best case for the payer and societal perspectives, respectively.

Tahami et al also explored the effect of treatment stopping rules and alternative treatment dosing. All told, the model predicted lower QALYs gained and lower values in 2 scenarios that used lecanemab for 1.5 years, 1 of which had treatment stopped with no residual benefit, and 1 of which achieved amyloid reduction that was maintained over a lifetime even after discontinuation. When patients were assumed to switch to a less frequent maintenance dosing schedule from biweekly dosing in the initial 1.5 years to once every 4 weeks in the maintenance phase assuming similar treatment effect to the base case, the estimated economic value increased by 44% for both payer and societal perspectives.

An antiamyloid therapy, lecanemab received FDA approval to treat early stages of AD in early January; however, there remain issues with accessing the medication, as the Centers for Medicare and Medicaid Services have not budged on their coverage stance for these agents. Originally approved under the accelerated approval pathway, Eisai is expected to hear a decision from the FDA on the traditional approval of lecanemab on July 6, 2023.³

REFERENCES
1. Eisai publishes societal value of lecanemab using phase 3 Clarity AD data in peer-reviewed neurology and therapy journal. Eisai. News release. March 19, 2023. Accessed March 24, 2023. https://www.prnewswire.com/news-releases/eisai-publishes-societal-value-of-lecanemab-using-phase-3-clarity-ad-data-in-peer-reviewed-neurology-and-therapy-journal-301775674.html
2. Monfared AAT, Ye W, Sardesai A, et al. Estimated societal value of lecanemab in patients with early Alzheimer’s disease using simulation modeling. Neurol and Ther. Published online March 16, 2023. doi:10.1007/s40120-023-00460-1
3. FDA Accepets Eisai’s filing of a supplemental biologics license application and grants priority review for traditional approval of Leqembi (lecanemab-irmb) for the treatment of Alzheimer’s disease. News release. Eisai. March 5, 2023. Accessed March 24, 2023. https://www.prnewswire.com/news-releases/fda-accepts-eisais-filing-of-a-supplemental-biologics-license-application-and-grants-priority-review-for-traditional-approval-of-leqembi-lecanemab-irmb-for-the-treatment-of-alzheimers-disease-301762846.html