Alzheimer Disease Drugs Show Double the Impact in Long-Term Extension Results
Patients with early Alzheimer disease (AD) treated with lecanemab (Leqembi; Eisai Co. and Biogen Inc.) and donanemab (Kisunla; Eli Lilly and Company) experienced a higher degree of reduced cognitive decline in clinical trial extension studies compared with 18-month results from the core trials. Researchers presented 3- and 4-year data at the recent Alzheimer’s Association International Conference in Toronto, Canada.
In the long-term extension (LTE) of the phase 3 TRAILBLAZER-ALZ 2 study, patients with early symptomatic AD continuously treated with donanemab, as well as those switched to donanemab from placebo in the core trial, demonstrated slowing of cognitive decline compared with an untreated external cohort from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
Compared with a 0.6-point drop vs placebo on the Clinical Dementia Rating Sum of Boxes (CDR-SB) at 18 months, patients who continued donanemab in the LTE showed a 1.2-point decrease at 36 months vs the untreated ADNI group. Earlier initiation of donanemab in participants reduced the risk of progression to the next stage of disease by 27% on the Clinical Dementia Rating-Global Score compared with patients who started donanemab later, Eli Lilly and Company reported.
>>NEWS: Multiple Sclerosis May Increase Risk for Alzheimer Disease
In the phase 3 Clarity AD core study of patients with early AD, the 18-month mean change in CDR-SB between the lecanemab group and the placebo group was -0.45 points.
“To provide context, a change from 0.5 to 1 on the CDR score domains of memory, community affairs, and home/hobbies reflects a shift from mild impairment to loss of independence,” Eisai and Biogen explained in a news release. “This can affect a person’s ability to be left alone safely, recall recent events, participate in daily activities, manage household tasks, and engage in hobbies and intellectual interests.”
In the open-label extension, patients continuously treated with lecanemab through the core and OLE demonstrated a 1.01-point drop on the CDR-SB at 36 months compared with the ADNI cohort. At 48 months, the benefit was even more pronounced: a 1.75-point drop compared with the ADNI cohort.
Compared with patients with mild cognitive impairment from the BioFINDER cohort, lecanemab showed a 1.40-point decrease at 36 months and a 2.17-point decrease at 48 months, Eisai and Biogen reported.
Among Clarity AD participants with low baseline levels of tau accumulation in the brain, 69% showed no decline and 56% showed improvement on the CDR-SB at 48 months with lecanemab.
References
