Therapy Type: Small Molecule (timeline)
Target Type: Cholinergic System (timeline)
Condition(s): Alzheimer's Disease, Dementia with Lewy Bodies
U.S. FDA Status: Alzheimer's Disease (Phase 1), Dementia with Lewy Bodies (Phase 2)
Company: Allergan plc, Sosei Heptares
This small-molecule drug selectively activates the muscarinic acetylcholine receptor M1, which is expressed in the central nervous system and peripheral secretory glands. HTL0018318 was developed by Heptares Therapeutics, a subsidiary of the Sosei Group Corporation, headquartered in Tokyo. Allergan Pharmaceuticals, headquartered in Dublin, licensed the rights to it in 2016. The companies are jointly developing this compound as a symptomatic treatment for the cognitive deficits in Alzheimer’s disease.
In 2015 and 2016, Heptares ran two Phase 1 trials of HTL0018318 in Japan, in 84 and 28 participants, respectively (company press release, press release). In 2016 and 2017, Heptares ran two Phase 1 trials in London, one to evaluate bioavailability of three different doses in 37 healthy volunteers, and one to study single and multiple dose administration in 54 healthy volunteers. In 2018, Heptares ran a Phase 1b study in four European countries, comparing three doses to placebo given for four weeks in 60 AD patients as an add-on to standard of care.
In July 2018, Heptares listed a 12-week Phase 2 trial in Japan. It is designed to compare three doses of HTL0018318 against placebo in 172 people with dementia with Lewy bodies (DLB) who have never taken, or have stopped taking, acetylcholinesterase inhibitors. Measuring safety, cognitive impairment, and psychosis as outcomes, the trial was to start in August 2018; however, on September 18, 2018, Allergan and Sosei announced they were delaying this trial due to toxicology findings in nonhuman primates. In a nine-month dose-finding study, some animals developed tumors at doses higher than those used in humans. The companies have suspended development of HTL0018318, including a planned Phase 2 study in AD, while they investigate, but claimed that no serious adverse effects have emerged in the 310 people who have taken the drug so far (see company press release).
Last Updated: 11 Feb 2019
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