Multiple-dose ponezumab for mild-to-moderate Alzheimer's disease: Safety and efficacy
Jaren W Landen1, Sharon Cohen2, Clare B Billing1
1Pfizer Inc., Groton, CT, USA.
Alzheimer'S & Dementia (New York, N. Y.)
|October 26, 2017
Summary
Ponezumab, an anti-amyloid antibody, was safe but ineffective for treating mild-to-moderate Alzheimer's disease (AD). This study found no improvements in cognitive function or brain volume despite dose-dependent plasma antibody levels.
Area of Science:
- Neurology
- Immunotherapy
- Pharmacology
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder.
- Anti-amyloid antibodies are being investigated as potential AD therapeutics.
- Ponezumab targets amyloid plaques, a hallmark of AD pathology.
Purpose of the Study:
- To evaluate the safety and efficacy of multiple intravenous doses of ponezumab in patients with mild-to-moderate Alzheimer's disease.
- To assess the dose-dependent effects of ponezumab on amyloid biomarkers and clinical outcomes.
Main Methods:
- A two-part study involving randomized, placebo-controlled administration of ponezumab at various doses (0.1 to 8.5 mg/kg).
- 10 infusions over 18 months with a subsequent 6-month follow-up period.
- Monitoring of adverse events, plasma and cerebrospinal fluid (CSF) biomarkers, cognitive/functional outcomes, and brain volume.
Main Results:
- Ponezumab was generally safe and well-tolerated, with adverse events including falls and headaches.
- Dose-dependent increases in plasma ponezumab and plasma Aβ levels were observed.
- No significant changes in cerebrospinal fluid biomarkers, cognitive/functional measures, or brain volume were detected.
Conclusions:
- Multiple-dose ponezumab demonstrated a favorable safety profile in mild-to-moderate Alzheimer's disease.
- Ponezumab did not show efficacy in improving cognitive or functional outcomes.
- The study suggests that targeting amyloid with ponezumab in this patient population is not effective.
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