Long-Term Safety and Efficacy of Bapineuzumab in Patients with Mild-to-Moderate Alzheimer’s Disease: A Phase 2, Open-Label Extension Study

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.

Cite this article as:

Salloway Stephen , Marshall A. Gad , Lu Ming and Brashear Robert H.*, Long-Term Safety and Efficacy of Bapineuzumab in Patients with Mild-to-Moderate Alzheimer’s Disease: A Phase 2, Open-Label Extension Study, Current Alzheimer Research 2018; 15 (13) . https://dx.doi.org/10.2174/1567205015666180821114813