Therapy Type: Immunotherapy (passive) (timeline)
Target Type: APP and Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: Eisai Co., Ltd.
BAN2401 is a humanized IgG1 monoclonal antibody that binds selectively to large, soluble Aβ protofibrils and is thought to lead to their clearance or neutralize their toxicity. The therapeutic antibody was originally developed at the biotech company BioArctic Neuroscience following the discovery of the E22G “arctic” mutation in APP, which leads to a form of clinically typical Alzheimer's disease that is marked by particularly high levels of Aβ protofibrils (see Nilsberth et al., 2001).
A multicenter Phase 1 trial tested the safety, tolerability, and pharmacokinetics of single and multiple ascending intravenous doses of BAN2401 in 80 people with mild to moderate AD. Changes in Aβ levels were also tested. BAN2401 was reported to be well-tolerated at all doses tested up to 10mg/kg every two weeks, without incidents of amyloid-related imaging abnormalities (ARIA). The antibody entered the CSF and showed dose-dependent exposure. A Phase 2, 18-month U.S. trial is testing five different intravenous doses of BAN2401 in a Bayesian adaptive design, where allocation of subsequent enrollees to different groups will be adjusted in response to frequent interim analyses, the first to be done after the first 200 patients have entered the trial. This trial is enrolling up to 800 people who either have early stage AD as defined by the proposed NIA-AA diagnostic criteria of mild cognitive impairment due to AD, or who meet NIA-AA criteria for probable AD and whose diagnosis is confirmed by a positive amyloid PET scan. As a primary outcome, the trial will measure change in a composite of cognitive tests. See clinical trials of BAN2401 at clinicaltrials.gov.
Clinical Trial Timeline
- Nilsberth C, Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K, Forsell C, Stenh C, Luthman J, Teplow DB, Younkin SG, Näslund J, Lannfelt L. The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. Nat Neurosci. 2001 Sep;4(9):887-93. PubMed.
- CTAD: Adaptive Antibody Trial to Try Bayesian Statistics
- Barcelona: Antibody to Sweep Up Aβ Protofibrils in Human Brain
- Uppsala: Conference Puts Uppsala on Immunotherapy Map
- Philadelphia: The Enemy Within—Neurodegeneration From Intraneuronal Aβ
- San Diego: Oligomers Live Up to Bad Reputation, Part 2
- Philipson O, Hammarström P, Nilsson KP, Portelius E, Olofsson T, Ingelsson M, Hyman BT, Blennow K, Lannfelt L, Kalimo H, Nilsson LN. A highly insoluble state of Abeta similar to that of Alzheimer's disease brain is found in Arctic APP transgenic mice. Neurobiol Aging. 2009 Sep;30(9):1393-405. PubMed.