Therapeutics

Ponezumab

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Overview

Name: Ponezumab
Synonyms: PF-04360365
Therapy Type: Immunotherapy (passive) (timeline)
Target Type: Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease, Cerebral Amyloid Angiopathy
U.S. FDA Status: Alzheimer's Disease (Discontinued), Cerebral Amyloid Angiopathy (Phase 2)
Company: Pfizer
Approved for: None

Background

Ponezumab (PF-04360365) is a passive immunotherapy treatment originally developed by Rinat Neuroscience. It is a humanized IgG2δA monoclonal antibody that binds the free carboxy terminal amino acids 33-40 of the Aβ 1-40 peptide (see La Porte et al. 2012). This antibody drew widespread attention in 2006, when Pfizer acquired its original developer, the small biotech company Rinat Neuroscience, for a reported several hundred million dollars. 

Findings

Five Phase 1 trials tested ponuzemab's safety and pharmacokinetics in Western and Japanese patients with mild to moderate disease. They showed acceptable safety without findings of antibody-induced microhemorrhage, amyloid-related imaging abnormalities (ARIA), or encephalitis, but only a small proportion of the antibody was detectable in the CSF. Two Phase 2 trials concluded in 2011. One study of 198 patients with mild to moderate Alzheimer's confirmed adequate safety and showed a plasma Aβ40 increase with treatment, suggesting a peripheral sink effect. A second trial of 36 patients with mild to moderate AD, however, showed no effect on the primary endpoints of change in brain or CSF Aβ burden. Development of ponezumab for Alzheimer's disease was discontinued. Pfizer is, however, conducting a Phase 2 study of ponezumab in patients with cerebral amyloid angiopathy (CAA). For all ponezumab trials, see clincialtrials.gov

Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024
Pfizer NCT00722046
N=198
Pfizer NCT00945672
N=36

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References

Other Citations

  1. La Porte et al. 2012

External Citations

  1. clincialtrials.gov

Further Reading

Papers

  1. . Safety and pharmacology of a single intravenous dose of ponezumab in subjects with mild-to-moderate Alzheimer disease: a phase I, randomized, placebo-controlled, double-blind, dose-escalation study. Clin Neuropharmacol. 2013 Jan-Feb;36(1):14-23. PubMed.
  2. . Safety and pharmacology of ponezumab (PF-04360365) after a single 10-minute intravenous infusion in subjects with mild to moderate Alzheimer disease. Clin Neuropharmacol. 2013 Jan-Feb;36(1):8-13. PubMed.
  3. . Chronic Administration of an Aglycosylated Murine Antibody of Ponezumab Does Not Worsen Microhemorrhages in Aged Tg2576 Mice. Curr Alzheimer Res. 2012 May 22; PubMed.