Background

This is an active immunotherapy strategy. ACC-001 is a conjugate of multiple short Aβ fragments linked to a carrier made of inactivated diphtheria toxin. Vanutide cridificar is designed to avoid the safety concerns associated with the prior AN1792 active vaccine against full-length Aβ1-42.  Autoimmune meningoencephalitis caused by Th1 lymphocyte activation was attributed to Aβ residues 15–42. The Aβ fragments used in vanutide cridificar consist of amino acids 1–7. This N-terminal end contains a β cell epitope but is thought to avoid a T cell-mediated response against Aβ. Preclinical data indicate that vanutide cridificar generates N-terminal anti-Aβ antibodies but no Aβ-directed T cell response, and that it reverses cognitive impairment in murine models of AD. Elan research indicates that a small proportion of peripherally administered antibodies specific for Aβ peptide can cross the blood-brain barrier and act directly in the central nervous system to induce plaque clearance.

Findings

Vanutide cridificar was being tested in multiple Phase 2 trials, generally with a regimen of multiple injections over a year of doses ranging from 3–30 micrograms of vaccine, with or without the adjuvant QS-21. No results have been published in peer-reviewed journals. On July 14, 2013, at the Alzheimer's Association International Conference in Boston, researchers presented results of a trial in 40 patients in Japan with mild to moderate AD that found that co-administration of adjuvant was necessary to elicit a strong antibody response. This report indicated that the treatment was generally safe and well-tolerated, but noted one serious adverse event related to the study drug (see Arai et al., 2013). In August 2013, Pfizer's company pipeline listed this immunotherapy as having been discontinued from clinical development.

For details on all clinical trials of vanutide cridificar starting with Phase 1, see clinicaltrials.gov. 

Clinical Trial Timeline