Preliminary Analysis Of BAN2401 Effects On Brain Amyloid And ARIA-E Findings Over 12 Months Of Treatment In The Open-Label Extension Of The Phase2b Study BAN2401-G000-201 In Subjects With Early Alzheimer’s Disease
Chad Swanson1, Shobha Dhadda1, Mark Hodgkinson2, David Li1, Michio Kanekiyo1, June Kaplow1, Martin Rabe3, Helena Heanue-Travers2, Robert Gordon2, Robert YK Lai2, Lynn D. Kramer1
1Eisai Inc, 2Eisai Ltd, 3Eisai Inc.
To evaluate preliminary findings for BAN2401 to evaluate the longitudinal amyloid positron emission tomography (PET) and ARIA-E for 10 mg/kg biweekly (IV) BAN2401 in the ongoing OLE.
BAN2401 is a humanized IgG1 monoclonal antibody that selectively binds Aβ protofibrils and  has demonstrated dose-dependent reductions in brain amyloid in an18-month phase 2 study. 

Subjects received 10 mg/kg biweekly for up to 24 months. All subjects were required to be amyloid positive at baseline in the core study, based on positron emission tomography (PET) visual read or CSF. Regression analyses were conducted on amyloid PET standard uptake value ratio (SUVr) imaging data over 12 months during the OLE longitudinal period.  ARIA-E data were summarized according to observed events in the longitudinal OLE period.

A total of 180 subjects have been dosed in the OLE, where 143 subjects contributed to the current OLE longitudinal amyloid PET imaging dataset (Core allocation: placebo:45; 10 mg/kg monthly:60; 10 mg/kg biweekly:38). Reductions appeared to be dependent on Core treatment, with Core placebo-treated subjects showing model estimated reduction on PET SUVr of -0.08, -0.17, and -0.33 at 3, 6, and 12 months, respectively.  Point estimate reductions for Core BAN2401 treated subjects were lower over the 12-month OLE time course, dependent on starting OLE baseline PET SUVr values.  In the OLE, 14/180 (7.8%) dosed subjects across all Core treatment assignments have had ARIA-E to date .  ARIA-E occurred in 8.9% in Core placebo-treated patients, all of which were ApoE4+.
In this preliminary analysis, 10 mg/kg biweekly BAN2401 rapidly reduced brain amyloid in Core placebo-treated subjects as early as 3 months, with continued reduction over 12 months of treatment in the OLE.  These findings suggest that 10 mg/kg biweekly BAN2401 can be initiated at the onset of treatment to elicit rapid reduction of brain amyloid with relatively low incidence of ARIA-E.