Vanutide Cridificar and the QS-21 Adjuvant in Japanese Subjects with Mild to Moderate Alzheimer's Disease: Results from Two Phase 2 Studies

Objective: Multiple lines of evidence indicate that pathological accumulation of amyloid beta (A beta) peptide in the brain is linked to the pathophysiology of Alzheimer's disease (AD). Removal of A beta from the brain by binding to anti-A beta specific antibodies is under active investigation. Vaccination with a full-length A beta(42) peptide (AN1792) successfully elicited anti-A beta antibodies in human subjects with AD, but was associated with meningoencephalitis. To avoid this safety issue, an aminoterminal A beta(1-7) peptide conjugate, vanutide cridificar (ACC-001), was designed and is currently in clinical development. This report describes two phase 2 multiple ascending-dose studies in Japanese subjects with mild to moderate AD. Safety and immunogenicity evaluation were the primary and secondary objectives, respectively. Methods: ACC-001 was administered to three cohorts of subjects at doses of 3, 10, or 30 mu g, with or without a QS-21 adjuvant in Study 1, and with a QS-21 adjuvant in Study 2; control groups consisted of QS-21 alone (both studies) and phosphate-buffered saline (Study 1 only). Results: A variety of treatment-emergent adverse events (TEAEs) were reported from most subjects during the studies; most of these were mild or moderate in intensity. Three subjects withdrew from the study because of an adverse event (in Study 2). The most common treatment-associated TEAE was injection site reactions. No deaths were observed in either study. All doses of ACC-001 + QS-21 elicited high, sustained anti-A beta antibody titers; QS-21 was necessary for this effect. Conclusion: These data will provide valuable information on further investigation of anti-A beta vaccine therapy for AD.