An investigational subcutaneous autoinjector showed comparable efficacy and safety to the IV formulation of lecanemab (Leqembi) for maintenance treatment in early Alzheimer's disease, researchers said here.
Continued lecanemab treatment with 360 mg subcutaneous dosing resulted in a similar additional reduction of amyloid PET over 4 years of treatment as continuing biweekly IV lecanemab, reported Larisa Reyderman, PhD, of drugmaker Eisai, at the Alzheimer's Association International Conference (AAIC).
There were no differences in clinical outcomes including Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores between continued biweekly IV doses and 360 mg subcutaneous maintenance dose regimens, Reyderman said.
Weekly dosing with the 360 mg subcutaneous formulation maintained plasma biomarkers of amyloid-beta, glial fibrillary acidic protein (GFAP), and phosphorylated tau 181 (p-tau181), she added.
"Transitioning to weekly 360 mg subcutaneous autoinjector maintenance dosing after 18 months is similar to continuing IV 10 mg/kg biweekly dose for maintaining amyloid reduction and clinical efficacy," Reyderman stated.
Subcutaneous dosing can reduce the burden for patients and caregivers while still maintaining the efficacy observed with lecanemab biweekly treatment, she added.
"Modeling indicates that maintenance therapy with subcutaneous lecanemab prevents biomarker re-accumulation and has no significant meaningful impact on amyloid or meaningful impact on disease progression compared to the intravenous regimen," she said.
Lecanemab is a monoclonal antibody with high affinity to amyloid-beta soluble protofibrils. It was approved in 2023 as an IV infusion for early symptomatic Alzheimer's disease with IV maintenance dosing also approved.
The FDA approval's was based on the phase III CLARITY AD trial in which lecanemab reduced amyloid and slowed clinical decline on several measures of cognition and function, including CDR-SB scores at 18 months.
Lecanemab comes with a boxed warning about amyloid-related imaging abnormalities (ARIA), including ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). ARIA is usually asymptomatic but can be fatal. The lecanemab label also indicates that serious intracerebral hemorrhages greater than 1 cm have occurred in patients treated with monoclonal antibodies directed against aggregated forms of beta amyloid.
At AAIC, Eisai researchers discussed whether a subcutaneous lecanemab autoinjector might be an effective maintenance treatment option after 18 months of IV therapy. Clinical trials of subcutaneous lecanemab were conducted as a substudy of the open-label extension of the CLARITY AD study.
The safety profile of 360 mg weekly subcutaneous maintenance dosing was consistent with that of IV maintenance therapy, reported Eisai's Michael Irizarry, MD. Across all subcutaneous doses tested, the rate of systemic injection or infusion reactions was 1%, compared with 26% for IV dosing.
The 360 mg subcutaneous maintenance dose was initiated after 18 months of IV treatment, beyond the typical high-risk period for ARIA. Among 49 people treated with a 360 mg subcutaneous weekly maintenance dose of lecanemab for a mean of 6 months, there were no cases of ARIA-E and one case of ARIA-H. One intracerebral hemorrhage greater than 1 cm occurred in the 360 mg subcutaneous group that was not included in the ARIA-H data. "There were no new deaths related to amyloid-related imaging abnormalities," Irizarry said.
Other studies showed that most participants (95%) successfully administered the maintenance dose and most said the autoinjector was easy to use. The FDA is expected to decide whether to approve the lecanemab subcutaneous autoinjector by August 31.
In a separate AAIC session, Christopher van Dyck, MD, of Yale University in New Haven, Connecticut, reviewed the long-term safety and efficacy of lecanemab treatment from CLARITY AD and its open-label extension.
Over 4 years of treatment, lecanemab demonstrated a reduction in cognitive decline based on CDR-SB scores compared with the expected decline from a matched cohort from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Similarly, lecanemab showed a reduction in cognitive decline at 4 years versus the expected decline in the Swedish BioFINDER cohort.
Benchmarked against ADNI, 4 years of lecanemab treatment reduced the relative risk of progression to the next stage of Alzheimer's disease by 34%. In a subset of CLARITY AD participants with low tau, more than half (56%) had improvement on CDR-SB after 4 years of lecanemab therapy, van Dyck noted.
"In CLARITY AD, the observed increasing treatment difference with ongoing lecanemab treatment in participants treated through 48 months versus matched controls -- ADNI and BioFINDER -- is consistent with a disease-modifying effect," he said. The long-term safety profile of lecanemab was confirmed, with no new safety signals, he added.
The new data expanded lecanemab's 3-year findings that van Dyck showed at the 2025 American Academy of Neurology meeting.
Disclosures
All studies were supported by Eisai.
Reyderman and Irizarry are Eisai employees.
Van Dyck reported relationships with Roche, Eisai, Ono Pharmaceuticals, Cerevel, Bristol Myers Squibb, UCB, Eli Lilly Janssen Pharmaceuticals, Biogen, and Genentech.
Primary Source
Alzheimer's Association International Conference
Source Reference: Reyderman L "Lecanemab subcutaneous formulation for maintenance dosing in early Alzheimer's disease" AAIC 2025; Abstract 104693.
Secondary Source
Alzheimer's Association International Conference
Source Reference: Irizarry M "Safety profile of a subcutaneous lecanemab formulation" AAIC 2025.
Additional Source
Alzheimer's Association International Conference
Source Reference: van Dyck C "The lecanemab CLARITY AD open-label extension in early Alzheimer's disease: Initial findings from the 48-month analysis" AAIC 2025.
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