Name: BAN2401
Synonyms: mAb158
Therapy Type: Immunotherapy (passive) (timeline)
Target Type: Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 3)
Company: Biogen, Eisai Co., Ltd.


BAN2401 is the humanized IgG1 version of the mouse monoclonal antibody mAb158, which selectively binds to large, soluble Aβ protofibrils. The therapeutic antibody was originally developed at the biotech company BioArctic Neuroscience following the discovery of the “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 and relative absence of amyloid plaques (see Nilsberth et al., 2001). mAB158 was found to reduce Aβ protofibrils in brain and CSF of Tg-ArcSwe mice (Tucker et al., 2015). Subsequent studies in mouse neuron-glial co-cultures showed that mAb158 may protect neurons, i.e., reduce Aβ protofibril toxicity, by counteracting the pathological accumulation of these protofibrils in astrocytes (Söllvander et al., 2018).

BAN2401 was licensed to Eisai, which in March 2014 signed a collaboration agreement with Biogen for joint development of this therapeutic antibody.


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 measured. BAN2401 was well-tolerated at all doses tested, up to 10mg/kg every two weeks for four months, with amyloid-related imaging abnormalities (ARIA-E, ARIA-H) occurring at the same rate in both placebo and BAN2401. The antibody entered the CSF and showed dose-dependent exposure, though with a short serum elimination half-life of seven days and no clear effect on CSF biomarkers. Results were formally published (Logovinsky et al., 2016).

Subsequently, a Phase 2, 18-month U.S. trial tested five different intravenous doses of BAN2401 in a Bayesian adaptive design. Allocation of subsequent enrollees to different groups was adjusted in response to frequent interim analyses, the first to be done in late 2015 after the first 196 patients had entered the trial, and again every time 50 more people had enrolled (for detailed description of this innovative trial design see Satlin et al., 2016). This trial enrolled 856 people who either had early stage AD as defined by the proposed NIA-AA diagnostic criteria or mild cognitive impairment due to AD, or who met NIA-AA criteria for probable AD and whose diagnosis was confirmed by a positive amyloid PET scan. As primary outcomes, the trial measured 12-month change from baseline in the new ADCOMS composite of cognitive tests (Wang et al., 2016), and safety.

In 2017 the sponsors announced that BAN2401 had shown no cognitive benefit at this 12-month time point. However, futility conditions had not been met either at the 17 interim analyses conducted until then. Therefore the trial continued to full enrollment of 856 participants, and out to the full treatment period of 18 months (Dec 2017 news). In February 2018, the trial protocol was amended to offer up to five years of additional treatment in an open-label extension phase, in which change on the ADCOMS will be measured at each visit. Results of the blinded 18-month treatment phase were expected by end of 2018.

The sponsors announced top-line results of the blinded 18-month treatment phase in July 2018 (see news). The highest antibody dose of twice-monthly 10 mg/kg slowed progression on the ADCOMS and reduced brain amyloid accumulation, according to a press release from BioArctic.

Full results were presented at AAIC (Jul 2018 news). The antibody reduced brain amyloid by up to 93 percent in the highest-dose group. This dose slowed cognitive decline by 47 percent on the ADAS-Cog, and by 30 percent on the ADCOMS. The next lower dose, 10 mg/kg monthly, showed a trend toward slower cognitive decline that was not statistically significant. In an analysis of CSF from a subgroup of patients, the treatment caused a dose-dependent rise in CSF Aβ42. MRI scans detected ARIA in just under 10 percent of participants overall, and in fewer than 15 percent of those with ApoE4 in the highest-dose group. Most ARIA occurrences were asymptomatic.

The results were complicated by uneven distribution of ApoE4 carriers between placebo and treatment groups, which was caused by an EMA request during the trial. A subgroup analysis, presented at the Clinical Trials on Alzheimer Disease conference, suggested that the treatment benefit was not due to this imbalance (Nov 2018 news).

An open-label extension to the Phase 2b trial will re-enroll its participants and deliver the highest antibody dose for up to two years total. As reported at AD/PD 2019 in Lisbon, Portugal, Eisai/Biogen plan to treat up to 250 people in the extension, which will run until August 2021 (May 2019 news).

In March 2019, Eisai began a Phase 3 trial called Clarity AD. It aims to enroll 1,566 people with early symptomatic AD, who will receive 10 mg/kg drug or placebo every two weeks for 18 months, followed by open-label extension to 45 months. The primary outcome in the core study will be change in CDR-SB at 18 months, with secondary outcomes of brain amyloid, ADCOMS and ADAS-Cog14 subscale. In the extension phase, primary outcomes will be change in CDR-SB as well as safety and change in CSF biomarkers neurogranin, neurofilament light chain, Aβ(1-42), total Tau and phospho-Tau from baseline up to 45 months. The trial is set to run until 2024.

In February 2020, the Alzheimer’s Therapeutic Research Institute announced that the Alzheimer's Clinical Trial Consortium (ACTC) would conduct a large BAN2401 study co-funded by the NIH and Eisai (press release). Called Ahead 3-45 and expected to start in July 2020, this four-year trial comprises two sub-studies in a combined 1,400 people who are cognitively normal but have elevated brain amyloid. A3 will enroll 400 people with amyloid below the brain-wide threshold for positivity; they will received low-dose BAN2401 or placebo every four weeks for 216 weeks and their primary outcome will be change in brain amyloid PET at that time. A45 will enroll 1,000 participants who have a positive amyloid PET scan. They will receive high-dose BAN2401 every two weeks for 96 weeks, followed by low-dose treatment, and their primary outcome is change from baseline on their Preclinical Alzheimer Cognitive Composite 5 (PACC5) Score, also at week 216.

For all clinical trials of BAN2401, see

Clinical Trial Timeline

  • Phase 1
  • Phase 2
  • Phase 3
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Eisai Co., Ltd. NCT01230853
Eisai Co., Ltd. NCT01767311
Eisai Co., Ltd. NCT03887455

Last Updated: 16 Jul 2020


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News Citations

  1. No Man’s Land: Neither Early Success nor Failure for BAN2401
  2. Topline Results: 18 Months of BAN2401 Might Work
  3. BAN2401 Removes Brain Amyloid, Possibly Slows Cognitive Decline
  4. Second Look at BAN2401 Data Still Positive, Despite Snafu
  5. Keep Your Enthusiasm? Scientists Process Brutal Trial Data

Research Models Citations

  1. Tg-ArcSwe

Paper Citations

  1. . Safety and tolerability of BAN2401--a clinical study in Alzheimer's disease with a protofibril selective Aβ antibody. Alzheimers Res Ther. 2016 Apr 6;8(1):14. PubMed.
  2. . Design of a Bayesian adaptive phase 2 proof-of-concept trial for BAN2401, a putative disease-modifying monoclonal antibody for the treatment of Alzheimer's disease. Alzheimers Dement (N Y). 2016 Jan;2(1):1-12. Epub 2016 Feb 4 PubMed.
  3. . ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials. J Neurol Neurosurg Psychiatry. 2016 Sep;87(9):993-9. Epub 2016 Mar 23 PubMed.
  4. . The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. Nat Neurosci. 2001 Sep;4(9):887-93. PubMed.
  5. . The murine version of BAN2401 (mAb158) selectively reduces amyloid-β protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice. J Alzheimers Dis. 2015;43(2):575-88. PubMed.
  6. . The Aβ protofibril selective antibody mAb158 prevents accumulation of Aβ in astrocytes and rescues neurons from Aβ-induced cell death. J Neuroinflammation. 2018 Mar 28;15(1):98. PubMed.

Other Citations

  1. “Arctic” mutation

External Citations

  1. press release from BioArctic.
  2. press release

Further Reading


  1. . 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.
  2. . Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease. Alzheimers Res Ther. 2014;6(2):16. Epub 2014 Mar 24 PubMed.
  3. . Are antibodies directed against amyloid-β (Aβ) oligomers the last call for the Aβ hypothesis of Alzheimer's disease?. Immunotherapy. 2019 Jan;11(1):3-6. PubMed.