Therapy Type: Small Molecule
Target Type: Cholinergic System
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
ABT-126 is an α-7 nicotinic acetylcholine receptor (α7-nAChR) allosteric modulator that is being developed for the treatment of Alzheimer's disease and the cognitive deficits in schizophrenia. 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 is 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 is 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. Few results have been publicly disclosed.
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 compared two undisclosed doses of ABT-126 in nearly 300 people with mild to moderate AD to placebo and to donepezil, but without co-administration of ABT-126 to donepezil. This trial ended in 2010 and in 2013 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 Conference story).
Subsequently, AbbVie started two 24-week Phase 2b trials in 400 patients each. One is comparing three reportedly higher, but undisclosed, doses of ABT-126 to donepezil and to placebo, the other is comparing two undisclosed doses to placebo. Each trial offers a 28-week open-label extension to people who have completed the blinded portion of the study. These studies are expected to read out in 2014.
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 are ongoing. One compares two doses to placebo in 150 patients for 12 weeks at sites in the United States; the other is 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. 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
No Available Further Reading