Lecanemab Clinical Trials

What Is Lecanemab?

Lecanemab is an FDA-approved medication for Alzheimer's disease. It is an active ingredient in an injection concentrate solution, administered intravenously. This medication is considered a disease-modifying therapy, working to address the underlying pathology of Alzheimer's by targeting the accumulation of amyloid plaques in the brain. By reducing these plaques, lecanemab aims to slow cognitive decline and improve the ability to perform daily activities. It is also being studied for other related conditions.

Uses and Conditions Under Study

Lecanemab is primarily studied for Alzheimer's disease and related cognitive impairments. This neurodegenerative condition is characterized by cognitive decline, impaired daily function, and the accumulation of amyloid plaques in the brain. Lecanemab, as a disease-modifying therapy, targets these amyloid plaques to potentially slow disease progression. It is being investigated across 17 trials for various forms of Alzheimer's disease, including familial types, as well as for general dementia and mild cognitive impairment (MCI), which can be a precursor to Alzheimer's. Additionally, some studies involve healthy volunteers to assess the drug's safety and how it moves through the body.

Dosing

Lecanemab is administered as an injection concentrate solution for intravenous infusion, typically given over 60 minutes. It is also being studied as a subcutaneous injection. Various dosages have been investigated in clinical trials. Intravenous doses include 10 mg/kg, 5 mg/kg, and 2.5 mg/kg, which have been studied biweekly or monthly. Other specific doses such as 720 mg and 700 mg have also been explored. For the subcutaneous form, different doses are under investigation in extension phases of studies. These varied dosing regimens aim to determine the most effective and safe way to administer lecanemab for Alzheimer's disease.

Side Effects

In a clinical trial involving 789 patients treated with Lecanemab for early Alzheimer's disease, the most common side effects observed were infusion-related reactions and headache. These side effects were reported more frequently in patients receiving Lecanemab compared to those on placebo.

• Infusion-related reactions occurred in 18.6% of patients taking Lecanemab, compared to 3.3% on placebo. These reactions can include flu-like symptoms, chills, rash, and shortness of breath.
• Headache was reported by 14.3% of patients on Lecanemab, versus 10.2% on placebo.
• Falls occurred in 13.6% of patients receiving Lecanemab, compared to 11.4% on placebo.
• Diarrhea was experienced by 8.0% of patients on Lecanemab, versus 4.9% on placebo.
• Cerebral microhaemorrhage (small bleeds in the brain) occurred in 6.6% of patients taking Lecanemab, compared to 4.9% on placebo. This is a type of amyloid-related imaging abnormality (ARIA).
• Contusion (bruising) was reported by 6.2% of patients on Lecanemab, versus 2.9% on placebo.

Other side effects, such as urinary tract infection, upper respiratory tract infection, nasopharyngitis, back pain, dizziness, and arthralgia, were reported at similar or lower rates in the Lecanemab group compared to the placebo group. It is important to discuss any side effects with your healthcare provider.

Clinical Trial Results

Clinical trials have evaluated the efficacy of Lecanemab in patients with early Alzheimer's disease. The primary study, NCT01767311, assessed changes in brain amyloid levels and clinical measures over 12 to 18 months.

Reduction in Brain Amyloid

In the core study phase, Lecanemab significantly reduced amyloid plaques in the brain, a hallmark of Alzheimer's disease. Patients receiving 10 mg/kg biweekly experienced an average reduction of approximately 63 to 72 centiloids in brain amyloid levels by months 12 and 18. In contrast, patients on placebo showed little change, with an average change of -2.154 to 1.004 centiloids.

The open-label extension (OLE) phase of the study further demonstrated amyloid reduction. Patients who were previously on placebo and then started Lecanemab (newly treated) showed substantial reductions in amyloid levels, ranging from approximately 51 to 67 centiloids from their OLE baseline. Patients who continued Lecanemab (re-treated) also showed further reductions, ranging from approximately 22 to 33 centiloids from their OLE baseline. The percentage of amyloid-positive participants also decreased significantly in both newly treated and re-treated groups over time.

Impact on Clinical Decline

Lecanemab also showed an effect on measures of cognitive and functional decline. The Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, which assesses the severity of dementia, showed a smaller increase (indicating less worsening) in patients treated with Lecanemab compared to placebo. At Month 18, patients on 10 mg/kg biweekly Lecanemab had an average CDR-SB score increase of 0.568, compared to an increase of 0.911 in the placebo group. Similarly, at Month 12, the Lecanemab group showed an increase of 1.102 compared to 1.499 for placebo.

The Alzheimer's Disease Composite Score (ADCOMS) also indicated less clinical decline with Lecanemab. At Month 18, patients on 10 mg/kg biweekly Lecanemab had an average ADCOMS score increase of 0.136, compared to an increase of 0.193 in the placebo group. At Month 12, the Lecanemab group showed an increase of 0.077 compared to 0.113 for placebo.

The Alzheimer Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) also showed a slower rate of cognitive decline in the Lecanemab group. At Month 18, patients on 10 mg/kg biweekly Lecanemab had an average ADAS-Cog score increase of 1.481, compared to an increase of 2.842 in the placebo group. At Month 12, the Lecanemab group showed an increase of 2.588 compared to 4.902 for placebo.

In the OLE phase, 173 participants on 10 mg/kg biweekly Lecanemab experienced treatment-emergent adverse events (TEAEs), and 60 experienced serious adverse events (SAEs).

Currently Recruiting Trials

Where to Participate

• Boston, Massachusetts
• Saint Paul, Minnesota

Development Timeline