A best-case analysis indicated that, for amyloid-positive patients diagnosed with MCI due to AD or mild AD dementia, lecanemab plus standard of care provided an additional gain of 0.75 in quality-adjusted life years.
Using the AD Archimedes condition-event (ACE) disease stimulation model, investigational agent lecanemab (BAN2401; Eisai) was estimated to slow the rate of disease progression, resulting in an extended duration of mild cognitive impairment (MCI) due to Alzheimer disease (AD) and mild AD dementia and shortened duration in moderate and severe AD dementia. After gaining fast track designation in June 2021, Eisai still anticipates completing lecanemab’s rolling submission of a biologics license application in the first quarter of the company’s fiscal year, which began April 1, 2022.1,2
Compared with standard of care (SoC) alone, the proportion of patients on lecanemab plus SoC who progressed to mild AD, moderate AD, and severe AD were reduced by 7%, 13%, and 10%, respectively. The model also predicted a 25% lifetime probability of needing institutional care for those who received the combination of treatments vs 31% for those on SoC alone.
"The findings from the simulation model suggest early treatment with lecanemab may delay progression to the more severe stages of AD, potentially giving people living with early AD and their loved ones more time together and possibly reducing healthcare costs,” Ivan Cheung, chairman and senior vice president, and president, Neurology Business Group and Global Alzheimer’s Disease Officer, Eisai, said in a statement.1 “These predicted and simulated long-term health outcomes provide insights for healthcare decision-makers regarding the potential clinical and socioeconomic value of lecanemab."
The analysis was of Study 201 (NCT01767311), a phase 2b proof-of-concept trial that originally showed a reduction in brain amyloid in lecanemab-treated patients. Those findings, as well as consistent reductions observed across several clinical and biomarker end points, were the basis for the FDA granting breakthrough therapy designation for the agent in June 2021.3
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In the current analysis, investigators aimed to measure the lifetime health outcomes of lecanemab in delaying the onset of AD dementia or clinical worsening in patients with early AD. The AD ACE disease equations developed from analyses of longitudinal patient-level data from the AD Neuroimaging Initiative (ADNI) dataset were used to model the natural history progression of AD for patients managed according to SoC. The model used Clinical Dementia Rating–Sum of Boxes (CDR-SB) thresholds to define AD severity levels for patients, as their predicted cognition level deteriorates over time.
All bast-case results were generated on the basis of a lifetime simulation of 2000 patients sampled from the ADNI patient profiles. At the end of the analysis, the mean time-to-event outcomes all increased for patients in the lecanemab plus SoC group vs SoC alone by increments of 2.51 years for mild AD, 3.13 years for moderate AD, and 2.34 years for severe AD. Of those alive, the incremental median times to mild and moderate AD were 0.87 and 3.44, respectively, although the median time was not reached for severe AD and institutional care.2
Treatment with lecanemab plus SoC resulted in an estimated 11.6 more years in community care and 0.13 fewer years in institutional care compared with those solely on SoC. This translated to an overall incremental survival of 1.03 years (lecanemab + SoC: 8.40 years; SoC: 7.37 years). When accounting for health discount, the model predicted incremental total life years (LYs) and quality-adjusted LYs (QALY) of 0.73 and 0.75, respectively, for lecanemab plus SoC vs SoC only.
In scenario analyses, initiating lecanemab in patients with early AD with a median baseline age of 65 years resulted in an additional QALY gain of 0.23 over a lifetime and a slight delay in progression to moderate AD dementia.
"Ongoing phase 3 studies will soon be able to inform the model inputs and refine the findings. As part of Eisai's commitment to our human healthcare mission and transparency, we will continue to publish data and information about lecanemab,” Cheung added.1
The ongoing phase 3 AHEAD 3-45 trial (NCT04468659), in conjunction with the Alzheimer’s Clinical Trials Consortium, aims to enroll 1400 participants with preclinical AD who will be treated with lecanemab for 216 weeks. In that program, patients undergo a common screening period followed by randomization to 1 of 2 trials: A3 and A45. The first of the trials, A45, will use change from baseline in the Preclinical Alzheimer Cognitive Composite 5 (PACC5) as the primary end point, whereas in A3, investigators will assess change in brain amyloid levels as measured by amyloid PET.4