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Name: AN-1792
Synonyms: AIP 001
Therapy Type: Immunotherapy (active) (timeline)
Target Type: Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: Janssen, Pfizer
Approved for: None


AN-1792 was the first active immunotherapy strategy for Alzheimer's disease. AN-1792 consists of synthetic full-length Aβ peptide with QS-21 adjuvant. The rationale was that AN-1792 would induce an immune response that would remove brain amyloid deposition. Extensive preclinical evidence showed that immunization with Aβ1-42 peptide can prevent or reverse the development of the neuropathological hallmarks of Alzheimer's disease, including  amyloid plaque formation, neuritic dystrophy, synaptic loss, gliosis, and impaired performance in behavioral assays (e.g. Schenk et al., 1999).


Dosing in a 372-patient, multinational Phase 2a trial in people with mild to moderate AD was suspended when four treated patients developed brain inflammation that later proved to be aseptic meningoencephalitis. Altogether, six percent of patients came down with this side effect. In 2002, development of AN-1792 was terminated, but follow-up assessment of treated patients continued.

Postmortem pathology examination of patients who had received AN-1792 in Phase 1 or 2a showed that the vaccine had markedly cleared plaque from the brain.  It did not clear neurofibrillary tangles. Postmortem pathology also showed T cell infiltration and inflammation around leptomeningeal blood vessels, especially near vascular amyloid (e.g. Nicoll et al., 2003). Only a minority of patients treated with AN-1792 mounted a significant antibody response, primarily with antibodies directed against the N-terminus of Aβ (see Lee et al., 2005). Eight responders from the Phase 1 trial were reported to have died from end-stage Alzheimer's disease despite brain amyloid clearance (see Holmes et al., 2008). In contrast, a 4.6 year follow up of 159 patients from the Phase 2a trial reported functional benefit in responders (see Vellas et al., 2009). Biomarker analysis in the AN-1792 program was limited. CSF assays reported a trend toward reduction in CSF phospho-tau concentrations in responders, and subsequent phospho-tau analysis of postmortem brain tissue reported a reduction of aggregated tau in neuronal processes (Boche et al., 2010). MRI scans at baseline and after treatment showed a transient increase in brain atrophy in responders, considered paradoxical at the time (see Jul 2004 conference story).

Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034
Janssen NCT00021723

Last Updated: 04 Mar 2016


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News Citations

  1. Philadelphia: Can a Shrinking Brain Be Good for You?

Paper Citations

  1. . Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med. 2003 Apr;9(4):448-52. PubMed.
  2. . Abeta42 immunization in Alzheimer's disease generates Abeta N-terminal antibodies. Ann Neurol. 2005 Sep;58(3):430-5. PubMed.
  3. . Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet. 2008 Jul 19;372(9634):216-23. PubMed.
  4. . Long-term follow-up of patients immunized with AN1792: reduced functional decline in antibody responders. Curr Alzheimer Res. 2009 Apr;6(2):144-51. PubMed.
  5. . Reduction of aggregated Tau in neuronal processes but not in the cell bodies after Abeta42 immunisation in Alzheimer's disease. Acta Neuropathol. 2010 Jul;120(1):13-20. PubMed.
  6. . Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature. 1999 Jul 8;400(6740):173-7. PubMed.

Further Reading


  1. . Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology. 2003 Jul 8;61(1):46-54. PubMed.
  2. . Neuropathology after active Abeta42 immunotherapy: implications for Alzheimer's disease pathogenesis. Acta Neuropathol. 2010 Sep;120(3):369-84. PubMed.
  3. . The biochemical aftermath of anti-amyloid immunotherapy. Mol Neurodegener. 2010;5:39. PubMed.
  4. . Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005 May 10;64(9):1553-62. PubMed.
  5. . Abeta vaccination effects on plaque pathology in the absence of encephalitis in Alzheimer disease. Neurology. 2005 Jan 11;64(1):129-31. PubMed.
  6. . An alternative method for estimating efficacy of the AN1792 vaccine for Alzheimer disease. Neurology. 2007 Nov 6;69(19):1868-72. PubMed.
  7. . Absence of beta-amyloid deposits after immunization in Alzheimer disease with Lewy body dementia. Arch Neurol. 2007 Apr;64(4):583-7. PubMed.
  8. . Effects of Abeta immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology. 2005 May 10;64(9):1563-72. PubMed.
  9. . Antibody responses, amyloid-beta peptide remnants and clinical effects of AN-1792 immunization in patients with AD in an interrupted trial. CNS Neurol Disord Drug Targets. 2009 Apr;8(2):88-97. PubMed.
  10. . A beta immunotherapy: Lessons learned for potential treatment of Alzheimer's disease. Neurodegener Dis. 2005;2(5):255-60. PubMed.