Optimal Subcutaneous Lecanemab Dose Found in Modeling Study
Lecanemab is an antibody-based therapy that eliminates toxic beta-amyloid clumps in the brain
The optimal dose of under-the-skin (subcutaneous) lecanemab, Eisai’s experimental therapy for early Alzheimer’s disease, has been determined in a modeling study.
The dose is currently being evaluated in the Phase 3 Clarity AD open-label extension study (NCT03887455).
“Eisai’s broad clinical program for lecanemab continues to deliver data regarding how lecanemab can be used as a potential disease-modifying treatment for patients with Alzheimer’s disease. The subcutaneous dosing currently being evaluated in the Clarity AD open-label extension study can potentially be of further benefit for patients,” Gunilla Osswald, CEO of BioArctic, said in a press release.
The study, “Subcutaneous dose selection of lecanemab for treatment of subjects with early Alzheimer’s disease,” was presented at the Alzheimer’s Association International Conference (AAIC) in San Diego, California, July 31–Aug. 4.
Lecanemab is an antibody-based therapy that selectively binds, neutralizes, and eliminates toxic beta-amyloid clumps in the brain.
The optimal intravenous (into-the-vein, IV) lecanemab dose was found in an 18-month Phase 2 clinical trial (NCT01767311) that examined its effectiveness, safety, and tolerability in 854 patients.
At a dose of 10 mg/kg, biweekly treatment with lecanemab resulted in a reduction in brain amyloid as well as a consistent reduction of decline across several clinical and biomarker endpoints.
A Phase 1 study compared the concentration of lecanemab in the blood after subcutaneous and IV dosing and found that, when administered under the skin, it was absorbed over a longer duration, reaching its peak concentration after 72 hours compared with one hour for IV dosing.
The safety and effectiveness of 10 mg/kg of IV lecanemab given biweekly are currently being investigated against a placebo in the Phase 3 Clarity AD study in people with mild Alzheimer’s disease.
In this study, researchers compared the safety and effectiveness of a fixed subcutaneous dose of lecanemab (720 mg weekly) with the IV dosing strategy of 10 mg/kg biweekly.
They also investigated how body weight impacts the amount of lecanemab patients are exposed to, the reduction in beta-amyloid plaques, and the incidence of amyloid-related imaging abnormality-E (ARIA-E) – adverse events related to lecanemab use that can manifest as brain edema.
They found the average concentration of lecanemab in patients’ blood was similar after subcutaneous and IV lecanemab, but the peak blood concentration of lecanemab was lower after subcutaneous dosing. Moreover, patients weighing less than 57kg had higher exposure, while those weighing more than 90 kg had lower exposure to subcutaneous lecanemab. For most individuals who weighed between 57-90 kg, exposures were comparable.
Subcutaneous lecanemab demonstrated similar tolerability and effectiveness to IV lecanemab, as measured by the reduction in beta-amyloid accumulation in the brain, for most patients weighing 57-90 kg. It also showed a good safety profile and was predicted to cause a lower incidence of ARIA-E because its peak concentration in the blood was lower than IV lecanemab.
This lower ARIA-E incidence was observed regardless of ApoE4 status, a known genetic risk factor for late-onset Alzheimer’s.
“This analysis demonstrates that fixed lecanemab SC [subcutaneous] dose of 720 mg administered weekly results in comparable exposure … and efficacy as measured by reduction in amyloid PET SUVr [positron emission tomography standard uptake ratio] to 10 mg/kg IV dose administered bi-weekly. SC lecanemab dose is predicted to have a lower incidence of ARIA-E compared to IV lecanemab due to lower [maximum concentration] following SC administration,” the researchers wrote.
“There is a great enthusiasm in the Alzheimer field for lecanemab and the other late-stage second-generation anti-amyloid antibodies with Phase 3 readouts in the coming months,” Osswald said. “We are eagerly looking forward to the topline data of the Clarity AD Phase 3 study this fall and the possibility of helping the Alzheimer community battle the disease.”
Pending data from the Clarity AD trial, which is expected this fall, the U.S. Food and Drug Administration is anticipated to decide about whether to approve lecanemab by Jan. 6, 2023.
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