Title:Long-Term Safety and Efficacy of Bapineuzumab in Patients with Mild-to-Moderate Alzheimer’s Disease: A Phase 2, Open-Label Extension Study
Volume: 15
Issue: 13
Author(s): Stephen Salloway, Gad A. Marshall, Ming Lu and H. Robert Brashear*
Affiliation:
- Janssen Research & Development, Pennington, NJ 08534,United States
Keywords:
Alzheimer's disease, bapineuzumab, MRI, brain amyloid-related imaging abnormality, AD assessment scale, disability
assessment for dementia.
Abstract: Background: Bapineuzumab is a humanized anti-amyloid-beta (Aβ) monoclonal antibody
directed at lowering the cerebral Aβ deposit in Alzheimer’s disease (AD).
Objective:This phase 2, open-label extension (OLE) study evaluated long-term safety and efficacy of
bapineuzumab in patients with the mild-to-moderate AD.
Methods: Patients (58-78 years) who completed either of two randomized, placebo-controlled, doubleblind
studies (subcutaneous [SC] single-dose-escalation, or intravenous (IV) multiple-ascending-dose))
entered the OLE. Three groups were assessed: bapineuzumab or placebo SC, and bapineuzumab (IV) in
OLE (bapi SC/bapi IV); bapineuzumab (IV) in Study 201 and OLE (bapi/bapi); and placebo in Study
201 and bapineuzumab IV in OLE (placebo/bapi).
Results: Of 194 patients enrolled, 158 withdrew from OLE; primarily due to withdrawal by subject
(n=85) and AE (n=30). Mean (SD) bapineuzumab exposure was 2.9 (1.90) years. There were no significant
differences for efficacy endpoints (AD Assessment Scale–cognitive subscale [ADAS-Cog], Disability
Assessment for Dementia [DAD] and MMSE scores) between the bapi/bapi and placebo/bapi
groups. Most patients (94.8%, 184/194) reported ≥1 treatment-emergent adverse events (TEAEs) in
OLE. Amyloid-related imaging abnormalities with effusion or edema (ARIA-E) occurred in 22 (11.3%)
patients. The most common TEAEs (>20% patients) were fall, agitation and urinary tract infection with
similar incidences between bapi/bapi and placebo/bapi groups.
Conclusion: No significant difference was seen in cognitive and functional decline between early and
delayed treatment groups. No new safety concerns emerged. ARIA-E incidence was higher in patients
first exposed to bapineuzumab in OLE versus previously exposed. No clear pattern of etiology contributed
to death events.
