A2-73 as a therapeutic for insomnia, anxiety and agitation
Inventors
Assignees
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Publication Number
US-12285403-B2
Publication Date
2025-04-29
Expiration Date
Abstract
A2-73 is a useful therapeutic in the treatment of humans suffering from insomnia, anxiety or agitation. Particular attention is made to oral daily doses of from about 10 mg to about 50 mg, with particular reference to about 20 to 30 mg.
Core Innovation
A2-73 (ANAVEX173; and also references A1-41 and A19-144) is described as a therapeutic for humans with insomnia, anxiety, and/or agitation, including Alzheimer’s disease-related insomnia and agitation. The document emphasizes oral daily dosing, with a stated dose range of about 10 to 30 mg and up to about 100 mg/day, and discusses daily versus every-other-day dosing schedules as illustrative regimens. A2-73 is further linked to receptor-mediated mechanisms involving b31 agonism and muscarinic agonism.
The background rationale in the provided content connects improved sleep to Alzheimer’s disease through amyloid beta physiology, including amyloid beta (Aβ) pathways, and describes mechanisms involving glutamate toxicity and oxidative stress. The described physiological context includes sleep fragmentation and REM and slow-wave sleep (SWS). The document indicates the goal of addressing sleep and behavioral symptoms using receptor-mediated modulation, including muscarinic receptors (M1–M2).
The document reports Phase 2a open-label study outcomes over 31 weeks in mild-to-moderate Alzheimer’s patients, with sustained or improved sleep and behavioral symptoms measured using HAM-D reductions, including insomnia, anxiety, and agitation components. It also describes stable cognitive and functional measures using MMSE and ADCS-ADL, attention/working memory improvements using Cogstate, and EEG/ERP P300 changes in a target detection and attention processing context. Safety and tolerability are noted, and additional benefit is described for systolic blood pressure control in hypertensive AD subjects.
Claims Coverage
The partial content includes two independent claims. Both claims center on therapeutically effective use of specific active pharmaceutical agents for concurrent treatment of insomnia and agitation, with the first claim directed to a dosage form and the second claim directed to a method of treating insomnia and agitation by administering such a dosage form.
Dosage form effective for concurrent insomnia and agitation
A dosage form comprising a therapeutically effective amount of an active pharmaceutical agent selected from tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine; tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (A2-73); tetrahydro-N,N-dimethyl-5,5-diphenyl-3-furanmethanamine; tetrahydro-N,N-dimethyl-5,5-diphenyl-3-furanmethanamine hydrochloride (A1-41); 1-(2,2-diphenyltetrahydrofuran-3-yl)-N-methylmethanamine; 1-(2,2-diphenyltetrahydrofuran-3-yl)-N-methylmethanamine hydrochloride (A19-144); and any combination thereof, wherein the therapeutically effective amount is effective for the concurrent treatment of insomnia and agitation in a subject in need thereof.
Administering dosage form for concurrent insomnia and agitation treatment
A method of treating insomnia and agitation in a subject in need thereof, comprising administering to the subject a dosage form comprising a therapeutically effective amount of an active pharmaceutical agent selected from tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine; tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (A2-73); tetrahydro-N,N-dimethyl-5,5-diphenyl-3-furanmethanamine; tetrahydro-N,N-dimethyl-5,5-diphenyl-3-furanmethanamine hydrochloride (A1-41); 1-(2,2-diphenyltetrahydrofuran-3-yl)-N-methylmethanamine; 1-(2,2-diphenyltetrahydrofuran-3-yl)-N-methylmethanamine hydrochloride (A19-144); and any combination thereof, wherein the therapeutically effective amount is effective for the concurrent treatment of insomnia and agitation in the subject.
Across the independent claims, the central inventive concept is the use of therapeutically effective amounts of the listed active pharmaceutical agents (including A2-73, A1-41, and A19-144 and combinations) in a dosage form that supports concurrent treatment of insomnia and agitation, either as a dosage form claim or as a method claim involving administration of that dosage form.
Stated Advantages
Improves sleep and behavioral symptoms in mild-to-moderate Alzheimer’s patients, with HAM-D reductions including insomnia, anxiety, and agitation components.
Maintains stable cognitive and functional measures (MMSE and ADCS-ADL) while addressing sleep/behavioral symptoms.
Improves attention/working memory measures (Cogstate) and produces EEG/ERP P300 changes in a target detection/attention processing context.
Provides additional benefit of systolic blood pressure control in hypertensive AD subjects.
Safety and tolerability are noted.
Documented Applications
Concurrent treatment of insomnia and agitation in a subject in need thereof.
Therapy for humans with insomnia, anxiety, and/or agitation, including Alzheimer’s disease-related insomnia and agitation.
Use in mild-to-moderate Alzheimer’s patients as described in a Phase 2a open-label study over 31 weeks, with outcomes including sleep/behavioral symptoms, cognition/functional measures, and EEG/ERP P300 changes.
Additional application to hypertensive Alzheimer’s subjects for systolic blood pressure control as described in Table 4.
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