The simulation model powered by Eisai’s Phase III Clarity AD trial data shows that lecanemab has improved long-term health outcomes compared to the standard of care (SoC) alone. The simulation suggests that patients with mild cognitive impairment due to Alzheimer’s disease (AD) have a slower rate of disease progression and remain in early AD stages longer.
The Phase III trial (NCT03887455) results replaced the previous simulation of long-term health outcomes that were based on data from a Phase IIb trial (NCT01767311).
An AD Archimedes condition-event (ACE) model was used to evaluate the effects of lecanemab on disease progression. AD ACE is a patient-level simulator that captures the management and pathophysiology of the disease. It simulates disease progression based on alterations in underlying markers, such as CSF Aβ and T-tau protein levels, brain cell metabolic activity, and hippocampal volume.
The model estimated that lecanemab slows down the progression of AD to moderate and severe stages. Patients with early AD that are treated with lecanemab and SoC gained 0.71 quality-adjusted life-years (QALY) and a 2.95-year delay in mean time to AD dementia progression. The analysis also showed a reduction of 0.11 years in institutional care and additional 1.07 years in community care.
Authors of the article that analyzed the simulation outlined that the key strengths of the simulation were that individual patient characteristics were used to better capture participant heterogeneity instead of using mean cohort characteristics.
However, the authors noted that the simulation may have certain limitations, as the study was based on amyloid PET levels, which were measured as a surrogate endpoint. The estimated mean time of disease progression from early AD to more severe states and QALY might be biased, “leading to an underestimation of uncertainty”.
Lecanemab received FDA’s accelerated approval in January 2023 based on Phase II data. It is currently marketed as Leqembi. The same month, Eisai submitted a supplemental Biologics License Application (sBLA) for traditional FDA approval. The agency accepted the sBLA and lecanemab was granted Priority Review with a Prescription Drug User Fee Act (PDUFA) date in June 2023. FDA plans to hold an Advisory Committee meeting to discuss the application but has not yet publicly announced the meeting date.
2022 was a chaotic year for AD clinical pipeline as the year was marked by the controversial approval of Aduhelm. Clinical Trials Arena reviewed AD drug development and what to look out for in 2023, as well as investigated the hunt for vaccines as a potential treatment for AD.