Delving into the Latest Updates on E-2027 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Irsenontrine, Irsenontrine maleate

+ [5]

Target

PDE9A

Mechanism

PDE9A inhibitors(Phosphodiesterase 9A inhibitors)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic Disease

Active Indication

Parkinson Disease

Inactive Indication

Dementia due to Parkinson's diseaseLewy Body Disease

Originator Organization

Eisai Co., Ltd.

Active Organization

Eisai Co., Ltd.

Inactive Organization

Eisai, Inc.

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC26H26N4O7

InChIKeyAFKSGMDXSLTKSU-DASCVMRKSA-N

CAS Registry1630083-70-3

This study will be conducted to compare Irsenontrine to placebo on the cognitive endpoint of Montreal Cognitive Assessment (MoCA) and the global clinical endpoint of Clinician's Interview Based Impression of Change Plus (CIBIC-Plus) Caregiver Input in participants with dementia with Lewy bodies after 12 weeks of treatment.

Start Date04 May 2018

Sponsor / Collaborator

Eisai, Inc.

100 Clinical Results associated with E-2027

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100 Translational Medicine associated with E-2027

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100 Patents (Medical) associated with E-2027

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4

Literatures (Medical) associated with E-2027

01 Oct 2023·Current Neurology and Neuroscience Reports

Lewy Body Dementia: An Overview of Promising Therapeutics

Review

Author: Sha, Sharon J ; Skylar-Scott, Irina A

PURPOSE OF REVIEWLewy body dementia (LBD) encompasses dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). This article will emphasize potential disease-modifying therapies as well as investigative symptomatic treatments for non-motor symptoms including cognitive impairment and psychosis that can present a tremendous burden to patients with LBD and their caregivers.RECENT FINDINGSWe review 11 prospective disease-modifying therapies (DMT) including four with phase 2 data (neflamapimod, nilotinib, bosutinib, and E2027); four with some limited data in symptomatic populations including phase 1, open-label, registry, or cohort data (vodabatinib, ambroxol, clenbuterol, and terazosin); and three with phase 1 data in healthy populations (Anle138b, fosgonimeton, and CT1812). We also appraise four symptomatic therapies for cognitive impairment, but due to safety and efficacy concerns, only NYX-458 remains under active investigation. Of symptomatic therapies for psychosis recently investigated, pimavanserin shows promise in LBD, but studies of nelotanserin have been suspended. Although the discovery of novel symptomatic and disease-modifying therapeutics remains a significant challenge, recently published and upcoming trials signify promising strides toward that aim.

01 Jul 2022·Alzheimer Disease & Associated Disorders

Confirmation of Target Engagement and Selection of Phase 2 Dose in Dementia With Lewy Bodies Trial

Article

Author: Aluri, Jagadeesh ; Reyderman, Larisa ; Landry, Ishani S. ; Boyd, Peter ; Ino, Mitsuhiro ; Horie, Kanta ; Lai, Robert ; Schuck, Edgar

Background:E2027 is a novel, highly selective and potent inhibitor of phosphodiesterase9 (PDE9) being evaluated as a treatment for dementia with Lewy bodies.Methods:Phase 1, randomized, double-blind, single ascending dose (SAD, n=96) and multiple ascending dose (MAD, n=68) studies evaluated E2027 doses (5 to 1200 mg) in healthy subjects. The impact of age, race (Japanese/non-Japanese), and food on pharmacokinetics (PK)/pharmacodynamics were evaluated. Serial cerebrospinal fluid (CSF) samples were collected to assess the target engagement.Results:E2027 PK profiles were biphasic (elimination half-life: ~30 hours. Approximately 3-fold accumulation was observed following multiple once-daily dosing. E2027 single doses of 50 to 400 mg resulted in mean maximum increases in CSF cyclic guanosine monophosphate ranging from 293% to 461% within 5.37 to 12.9 hours after dose administration to assess target engagement. Dose-response modelling of steady-state predose CSF cyclic guanosine monophosphate concentrations showed ≥200% increase from baseline is maintained with doses of ≥50 mg QD. The most common adverse events with E2027 were post-LP syndrome and back pain. PK profiles were similar between Japanese and non-Japanese. Higher exposure observed in fed versus fasted state was not considered clinically significant. PK exposure was higher in elderly subjects.Conclusions:S.E2027 was well-tolerated following single and multiple administration. E2027 achieved maximal and sustained target engagement at 50 mg QD, the dose selected for the phase 2 clinical trial.

01 Apr 2019·Drugs & AgingQ3 · MEDICINE

Pharmacological Management of Dementia with Lewy Bodies

Q3 · MEDICINE

Review

Author: Hershey, Linda A ; Coleman-Jackson, Rhonda

Dementia with Lewy bodies (DLB) is a complex disease that involves a variety of cognitive, behavioral and neurological symptoms, including progressive memory loss, visual hallucinations, parkinsonism, cognitive fluctuations and rapid eye movement sleep behavior disorder (RBD). These symptoms may appear in varying combinations and levels of severity in each patient who is seen in the clinic, making diagnosis and treatment a challenge. DLB is the third most common of all the neurodegenerative diseases behind both Alzheimer's disease and Parkinson's disease (PD). The median age of onset for DLB (76.3 years) is younger than that seen in PD dementia (81.4 years). New pathological studies have shown that most DLB patients have variable amounts of Alzheimer's changes in their brains, explaining the wide variability in this disease's clinical presentation and clinical course. This review discusses the three cholinesterase inhibitors that have been shown to be effective in managing the cognitive and behavioral symptoms of DLB: rivastigmine, galantamine and donepezil. Memantine is able to improve clinical global impression of change in those with mild to moderate DLB. Levodopa can treat the parkinsonism of some DLB patients, but the dose is often limited due to the fact that it can cause agitation or worsening of visual hallucinations. A recent phase 2 clinical trial showed the benefit of zonisamide when it is added as an adjunct to levodopa for treating DLB parkinsonism. While atypical antipsychotic drugs may not always be helpful as monotherapy in managing the agitation associated with DLB, low doses of valproic acid can be effective when added as an adjunct to drugs like quetiapine. Pimavanserin may prove to be a useful treatment for psychosis in DLB patients, but like other antipsychotic drugs that are used in dementia patients, there is a small increased risk of mortality. RBD, which is a common core clinical feature of DLB, can be managed with either melatonin or clonazepam. Two agents targeting alpha-synuclein (NPT200-11 and ambroxol) currently hold promise as disease-modifying therapies for DLB, but they are yet to be tested in clinical trials. An agent (E2027) that offers hope of neuroprotection by increasing central cyclic guanosine monophosphate (cGMP) levels is currently being examined in clinical trials in DLB patients.

100 Deals associated with E-2027

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Parkinson Disease	Phase 3	-	Eisai Co., Ltd.	-
Dementia due to Parkinson's disease	Discovery	US	Eisai, Inc.	25 Feb 2021
Dementia due to Parkinson's disease	Discovery	CA	Eisai, Inc.	25 Feb 2021
Lewy Body Disease	Discovery	IT	Eisai Co., Ltd.	19 Apr 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04764669 (CTgov)	Phase 2	Dementia due to Parkinson's disease \| Lewy Body Disease \| Parkinson Disease	34	E2027 (DLB Without Amyloid Copathology)	pjsvuszndr(jktvqroioc) = cobfpvmnvm hmmzoomgid (rfgqmeqakl, xsvctdbbra - zfkvmjslbf) View more	-	26 Sep 2022
NCT04764669 (CTgov)	Phase 2		34	E2027 (DLB With Amyloid Copathology)	pjsvuszndr(jktvqroioc) = kzdookhcbz hmmzoomgid (rfgqmeqakl, eygukebdsv - ooqmsqkszl) View more	-	26 Sep 2022
E2027 (AAIC2018)	Not Applicable	Lewy Body Disease	-	E2027 100 mg	cndvmmxddc(dyzdiwjnqb) = oagrkgwevv bsdjzkecqf (nbrgwnchoq )	-	01 Jul 2018