Therapy Type: Small Molecule (timeline)
Target Type: Cholinergic System (timeline)
Condition(s): Alzheimer's Disease, Schizophrenia
U.S. FDA Status: Alzheimer's Disease (Inactive), Schizophrenia (Inactive)
ABT-126 is an α-7 nicotinic acetylcholine receptor (α7-nAChR) allosteric modulator that was being developed to treat cognitive deficits in schizophrenia and Alzheimer's disease. Cholinergic function declines in Alzheimer's, and currently approved acetylcholinesterase-inhibitor therapies modestly improve cognitive deficits in patients with AD by way of boosting cholinergic transmission. The rationale of α7-nAChR agonists was that they will enhance cognition without causing side effects associated with overactivation of other nAChRs or muscarinic AChRs. ABT-126 was initially developed by Abbott Laboratories. In January 2013, Abbott spun out its pharmaceuticals business into a new company called AbbVie.
ABT-126 was in Phase 2 development for Alzheimer's disease in the United States, Canada, South Africa, and Eastern European countries, and in Phase 3 development for cognitive symptoms in schizophrenia in the United States and Europe.
For Alzheimer's disease, Phase 1 research for safety and pharmacology parameters started in healthy volunteers in 2009, and in patients with mild to moderate Alzheimer's in 2011. Also in 2009, a 12-week Phase 2 study in 274 people with mild to moderate AD compared 5 mg and 25 mg of ABT-126 to placebo and to donepezil, but without co-administration of ABT-126 and donepezil. This trial ended in 2010, and in 2013 preliminary data was reported to have shown good tolerability for ABT-126, with side effects similar to donepezil. A cognitive benefit for the higher dose similar to that seen with donepezil was reported, as well. The cognitive signal correlated with blood measures of exposure to ABT-126 (see Aug 2013 conference news). Full data were subsequently published open-access (Gault et al., 2015).
In 2012, AbbVie started two 24-week Phase 2b trials in 400 patients each, comparing doses ranging from 25 to 75 mg. One trial compared ABT-126 added on to donepezil to placebo, the other compared ABT-126 monotherapy to placebo. Preliminary results were published, suggesting that efficacy at these higher doses was insufficient to continue further development (Gault et al., 2014, and Othman et al., 2014). Each trial offered a 28-week, open-label extension to people who had completed the blinded portion of the study. These studies were due to read out in 2014, but have been terminated.
In schizophrenia, a 2009 Phase 1 trial evaluated safety and pharmacokinetics in 16 adult patients who were receiving treatment with an atypical antipsychotic. In 2010, a Phase 2 study compared two undisclosed doses to placebo in 207 adults with the disease. Two additional Phase 2 trials were added, one to compare two doses to placebo in 150 patients for 12 weeks at sites in the United States; the other as an international dose-ranging trial to compare three undisclosed doses to placebo in 430 patients for 24 weeks, with a one-year open-label extension. No results have been reported.
In October 2015, ABT-126 was absent from AbbVie's developmental pipeline for both indications. For a listing of ABT-126 trials, see clinicaltrials.gov.
Clinical Trial Timeline
- Phase 2
- Study completed / Planned end date
- Planned end date unavailable
- Study aborted
- Gault L, Ritchie CW, Robieson WZ, Pritchett Y, Othman AA, Lenza RA. A phase 2 randomized, controlled trial of the α7 agonist ABT-126 in mild-to-moderate Alzheimer's dementia. Volume 1, Issue 1, June 2015, Pages 81–90
- Gault LM, Meier A, Florian H, Gauthier S, Lin Y, Tang Q, Othman A. A Phase 2 Trial of the Efficacy and Safety of the Alpha7 Agonist Abt-126 as an Add-On Treatment in Mild-to-Moderate Alzheimer's Dementia. Alzheimer's & Dementia, Volume 10, Issue 4, Supplement, July 2014
- Othman A, Meier A, Ritchie CW, Florian H, Gault LM, Tang Q. Efficacy and Safety of the Alpha7 Agonist Abt-126 as a Monotherapy Treatment in Mild-To-Moderate Alzheimer's Dementia: Results of a Phase 2b Trial. Alzheimer's & Dementia Volume 10, Issue 4, Supplement, July 2014
No Available Further Reading