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Name: AGB101
Synonyms: levetiracetam
Chemical Name: (S)-α-Ethyl-2-oxo-1-pyrrolidineacetamide
Therapy Type: Small Molecule (timeline)
Target Type: Amyloid-Related (timeline)
Condition(s): MCI-AD
U.S. FDA Status: MCI-AD (Phase 2/3)
Company: AgeneBio, Inc.


AGB101 is a proprietary, once-daily, extended-release, low-dose formulation of the FDA-approved atypical anti-convulsant medication levetiracetam. According to AgeneBio, AGB101 corresponds to roughly 1/12 of the dose typically prescribed for epilepsy, and the drug's mechanism of action is inhibition of the synaptic protein SV2A. The rationale for AGB101’s use in MCI stems from suggestions that tamping down hippocampal neuron hyperactivity in people in the early stages of AD dementia may prevent the spread of tau pathology and disease progression.


In September 2015, AgeneBio received a $7.5 million grant from the National Institutes on Aging toward evaluating AGB101, and announced that it intended to begin a Phase 3 trial of this formulation in 2016 (company press releaseNov 2015 conference news). Further NIA funds were received in September 2017, a trial start announced for 2018 (press release), and the first patient enrolled in January 2019 (press release).

Conducted at 23 sites in the United States and Canada, the HOPE4MCI trial was intended to evaluate AGB101 safety, and its efficacy at slowing cognitive and functional impairment, in 830 people who fulfill criteria for MCI and have a positive PET scan for brain amyloid. Participants receive 220 mg AGB101 or placebo once daily for 78 weeks. The primary outcome is change in CDR-SB score at 78 weeks; secondary measures include change on the MMSE and Functional Activities Questionnaire. An imaging substudy  includes structural MRI and tau PET imaging with MK-6240 in 160 participants at baseline and after treatment; plasma p-217 will be measured at 78 weeks (Rosenzweig-Lipson et al., 2020). In August 2020, the trial registration was changed from Phase 3 to Phase 2/3. In April 2021, AgeneBio announced completion of enrollment in HOPE4MCI, with only 164 participants and 609 screen failures (press releaseAAIC presentation). The company now refers to the trial as a Phase 2b, rather than Phase 3, study. It finished in November 2022; results are expected in early 2023.

In April 2019, a Phase 2 research study on AGB101 began at Medical College of Wisconsin. This crossover trial compares the effects of two weeks of 220 mg/day AGB101 or placebo on functional brain networks. It will enroll 50 healthy older people, half ApoE4 carriers and half noncarriers. The primary endpoint will be change in functional connectivity in the hippocampus and default mode networks, assessed by functional MRI; secondary measures include tests of episodic memory. The study was completed in March 2021; the CTAD 2022 program listed an abstract but the poster was not shown.

For details on AGB101 trials, see

Last Updated: 02 Jan 2023


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News Citations

  1. Truly New to Déjà Vu: Investigational Therapy News at CTAD

Therapeutics Citations

  1. Levetiracetam

Paper Citations

  1. . HOPE4MCI trial: First trial targeting reduction of hippocampal overactivity to treat mild cognitive impairment due to Alzheimer’s disease with AGB101. Alzheimer's & Dementia, 07 December 2020 Alzheimer's & Dementia

External Citations

  1. company press release
  2. press release
  3. press release
  4. press release
  5. AAIC presentation

Further Reading


  1. . Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance. Neuroimage Clin. 2015;7:688-98. Epub 2015 Feb 21 PubMed.
  2. . Levetiracetam Alters Oscillatory Connectivity in Alzheimer's Disease. J Alzheimers Dis. 2017;58(4):1065-1076. PubMed.
  3. . Neurobehavioral characterization of APP23 transgenic mice with the SHIRPA primary screen. Behav Brain Res. 2005 Feb 10;157(1):91-8. PubMed.
  4. . Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci. 2009 Mar 18;29(11):3453-62. PubMed.
  5. . Antiepileptics Topiramate and Levetiracetam Alleviate Behavioral Deficits and Reduce Neuropathology in APPswe/PS1dE9 Transgenic Mice. CNS Neurosci Ther. 2013 Nov;19(11):871-81. PubMed.
  6. . Treatment strategies targeting excess hippocampal activity benefit aged rats with cognitive impairment. Neuropsychopharmacology. 2010 Mar;35(4):1016-25. PubMed.
  7. . Incidence and impact of subclinical epileptiform activity in Alzheimer's disease. Ann Neurol. 2016 Dec;80(6):858-870. Epub 2016 Nov 7 PubMed.