dalzanemdor (SAGE-718) / Sage Therapeutics - LARVOL DELTA

Huntington's disease clinical trials update: March 2025. (PubMed, J Huntingtons Dis) - "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing phase I clinical trial of ALN-HTT02 from Alynlam Pharmaceuticals. We also report on the SAGE-718 (also known as dalzanemdor) program from Sage Therapeutics, with results of the phase II DIMENSION study and the recent termination of the open-label phase III PURVIEW study. Additionally, we discuss recent developments in the regulatory pathway for AMT-130, following discussions between uniQure and the U.S. Food and Drug Administration regarding key aspects of accelerated approval. Finally, we provide a comprehensive listing of all currently registered and ongoing clinical trials in Huntington's disease."

Journal • Huntington's Disease • Movement Disorders

A Study to Evaluate the Safety and Tolerability of SAGE-718 in Participants With Huntington's Disease (clinicaltrials.gov) - P3 | N=153 | Terminated | Sponsor: Sage Therapeutics | N=300 ➔ 153 | Active, not recruiting ➔ Terminated; Internal company decision

Enrollment change • Trial termination • Huntington's Disease • Movement Disorders

A Study to Evaluate the Safety and Tolerability of SAGE-718 in Participants With Huntington's Disease (clinicaltrials.gov) - P3 | N=300 | Active, not recruiting | Sponsor: Sage Therapeutics | Trial completion date: Jul 2030 ➔ Jan 2025 | Trial primary completion date: Jul 2030 ➔ Jan 2025

Trial completion date • Trial primary completion date • Huntington's Disease • Movement Disorders

A Study to Evaluate the Safety and Tolerability of SAGE-718 in Participants With Huntington's Disease (clinicaltrials.gov) - P3 | N=300 | Active, not recruiting | Sponsor: Sage Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Huntington's Disease • Movement Disorders

Sage Therapeutics Announces Topline Results from the Phase 2 DIMENSION Study of Dalzanemdor (SAGE-718) in the Treatment of Cognitive Impairment Associated with Huntington’s Disease (Businesswire) - P2 | N=189 | DIMENSION (NCT05107128) | Sponsor: Sage Therapeutics | "The DIMENSION Study did not demonstrate a statistically significant difference from baseline in participants treated with dalzanemdor versus placebo on the SDMT, a measure of cognitive function, at Day 84, the primary endpoint. Dalzanemdor was generally well-tolerated and no new safety signals were observed. The majority of treatment emergent adverse events were mild to moderate in severity."

P2 data • Huntington's Disease

718-CIH-201: A Study to Evaluate the Effect of SAGE-718 on Cognitive Function in Participants With Huntington's Disease (HD) (clinicaltrials.gov) - P2 | N=189 | Completed | Sponsor: Sage Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Huntington's Disease • Movement Disorders

Sage Therapeutics Announces Strategic Reorganization to Prioritize ZURZUVAE Commercialization and Focus its Development Portfolio (Businesswire) - "Sage Therapeutics, Inc...today announced a strategic reorganization of its business operations to support the ongoing launch of ZURZUVAE in postpartum depression and focus pipeline development efforts ahead of a clinical study readout for dalzanemdor in Huntington’s Disease expected later this year. The reorganization is intended to enable Sage to strengthen its balance sheet, extend cash runway, and position the company for long-term growth potential."

Commercial • P2 data • CNS Disorders • Huntington's Disease • Postpartum Depression

Sage Therapeutics Announces Topline Results from the Phase 2 LIGHTWAVE Study of Dalzanemdor (SAGE-718) in the Treatment of Mild Cognitive Impairment and Mild Dementia in Alzheimer’s Disease (Businesswire) - "P2 | N=174 | LIGHTWAVE (NCT05619692) | Sponsor: Sage Therapeutics | "The LIGHTWAVE Study did not demonstrate a statistically significant difference from baseline in participants treated with dalzanemdor versus placebo on the Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) Coding Test score at Day 84, the primary outcome measure of the study. Based on these data, the Company does not plan further clinical development of dalzanemdor in AD...Dalzanemdor was generally well-tolerated and no new safety signals were observed. The majority of treatment emergent adverse events were mild to moderate in severity. Analyses did not demonstrate any meaningful differences in the dalzanemdor-treated group versus placebo in exploratory endpoints such as RBANS total score or MoCA total score."

P2 data • Alzheimer's Disease • CNS Disorders • Dementia

Huntington's Disease Pathogenesis, Molecular Factors, and Potential for Combinatorial Therapies: A Focus on BDNF and NMDA Receptor Therapies (MDS Congress 2024) - "Active clinical trials including SAGE-718, like other proposed therapeutic options for HD, have been investigated independently... HD is not defined by a single pathogenic process and therefore a single therapeutic target is unlikely to alleviate all pathogenic processes of a diversely acting mutant protein. Our paper builds on the literature by proposing a multi-faceted approach to treating HD."

CNS Disorders • Mental Retardation • Psychiatry • BDNF

718-CNA-202: A Study to Evaluate the Effects of SAGE-718 in Participants With Mild Cognitive Impairment or Mild Dementia Due to Alzheimer's Disease (AD) (clinicaltrials.gov) - P2 | N=174 | Completed | Sponsor: Sage Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Jan 2025 ➔ Jul 2024 | Trial primary completion date: Dec 2024 ➔ Jun 2024

Trial completion • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Sage Therapeutics Announces Second Quarter 2024 Financial Results and Highlights Pipeline and Business Progress (Businesswire) - "The Company expects the following milestones for ZURZUVAE in 2024: (i) 2024: Ongoing commercialization of ZURZUVAE in the treatment of women with PPD; Present analyses of real-world evidence for ZURZUVAE including health economics and patient reported outcomes....The Company expects the following milestones for dalzanemdor in 2024: (i) Late 2024: Report topline data from LIGHTWAVE Study in people with MCI and mild dementia due to AD; Report topline data from DIMENSION Study in people with HD cognitive impairment; (ii) 2024: Present additional analyses of data from the clinical development program as well as disease state and burden of disease research in HD and/or AD."

Clinical data • Commercial • P2 data • Patient reported outcomes • Real-world evidence • Alzheimer's Disease • Dementia • Huntington's Disease • Postpartum Depression

A Study to Evaluate the Effect of SAGE-718 on Cognitive Function in Participants With Huntington's Disease (HD) (clinicaltrials.gov) - P2 | N=178 | Active, not recruiting | Sponsor: Sage Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Huntington's Disease • Movement Disorders

Dalzanemdor (SAGE-718), a novel, investigational N-methyl-D-aspartate receptor positive allosteric modulator: Safety, tolerability, and clinical pharmacology in randomized dose-finding studies in healthy participants and an open-label study in participants with Huntington's disease. (PubMed, Clin Transl Sci) - "In HD participants, results suggest that dalzanemdor may improve cognitive performance on tests of executive function. These results support continued clinical development of dalzanemdor for the potential treatment of cognitive impairment in disorders of NMDAR hypofunction."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Huntington's Disease • Movement Disorders

A Study to Evaluate the Safety and Tolerability of SAGE-718 in Participants With Huntington's Disease (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Sage Therapeutics | Trial completion date: Dec 2025 ➔ Jul 2030 | Trial primary completion date: Dec 2025 ➔ Jul 2030

Trial completion date • Trial primary completion date • Huntington's Disease • Movement Disorders

Sage Therapeutics Announces Phase 2 SURVEYOR Study Reinforces Cognitive Impact of Huntington’s Disease (Businesswire) - P2 | N=69 | SURVEYOR (NCT05358821) | Sponsor: Sage Therapeutics | "The study met its primary endpoint demonstrating a statistically significant difference as measured by the HD-Cognitive Assessment Battery (HD-CAB) composite score at baseline between healthy participants and participants with Huntington’s Disease (HD) prior to any treatment with dalzanemdor (SAGE-718) or placebo....A total of 11 participants with HD experienced treatment emergent adverse events (TEAEs), the vast majority of which were mild to moderate in severity....The Company expects the following dalzanemdor program milestones in late 2024: Report topline data from LIGHTWAVE Study in mild cognitive impairment and mild dementia in Alzheimer’s Disease; Report topline data from DIMENSION Study in cognitive impairment associated with HD.."

P2 data • Alzheimer's Disease • CNS Disorders • Dementia • Huntington's Disease

28-Day Study of SAGE-718 on Functioning Capacity in Participants With Huntington's Disease (clinicaltrials.gov) - P2 | N=69 | Completed | Sponsor: Sage Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Sep 2024 ➔ Apr 2024 | Trial primary completion date: Sep 2024 ➔ Feb 2024

Trial completion • Trial completion date • Trial primary completion date • Genetic Disorders • Huntington's Disease • Movement Disorders

A Study to Evaluate the Effects of SAGE-718 in Participants With Mild Cognitive Impairment or Mild Dementia Due to Alzheimer's Disease (AD) (clinicaltrials.gov) - P2 | N=150 | Active, not recruiting | Sponsor: Sage Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Sage Therapeutics Announces Topline Results from Phase 2 PRECEDENT Study of Dalzanemdor (SAGE-718) in the Treatment of Mild Cognitive Impairment in Parkinson’s Disease (Businesswire) - P2 | N=86 | PRECEDENT (NCT05318937) | Sponsor: Sage Therapeutics | "Sage Therapeutics, Inc...announced today topline results from PRECEDENT, a double-blind, placebo-controlled Phase 2 study of the investigational oral medicine dalzanemdor (SAGE-718) in people with mild cognitive impairment (MCI) in Parkinson’s Disease (PD)....The PRECEDENT Study did not meet its primary endpoint of demonstrating statistically significant difference from baseline in participants treated with once-daily dalzanemdor versus placebo on the Wechsler Adult Intelligence Scale Fourth Edition-IV (WAIS-IV) Coding Test score at Day 42."

P2 data • CNS Disorders • Parkinson's Disease

28-Day Study of SAGE-718 on Functioning Capacity in Participants With Huntington's Disease (clinicaltrials.gov) - P2 | N=80 | Active, not recruiting | Sponsor: Sage Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Huntington's Disease • Movement Disorders

A Study to Evaluate the Effects of SAGE-718 in Participants With Parkinson's Disease Cognitive Impairment (clinicaltrials.gov) - P2 | N=86 | Completed | Sponsor: Sage Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Feb 2024 | Trial primary completion date: Jun 2024 ➔ Jan 2024

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease

Sage Therapeutics Announces Fourth Quarter and Full Year 2023 Financial Results and Highlights Pipeline and Business Progress (Businesswire) - "The Company expects the following milestones for dalzanemdor in 2024: Early 2024: Report topline data from PRECEDENT Study in people with MCI associated with PD; Mid-2024: Report topline data from SURVEYOR Study in people with HD cognitive impairment; Late 2024: Report topline data from LIGHTWAVE Study in people with MCI and mild dementia due to AD; Report topline data from DIMENSION Study in people with HD cognitive impairment..."

P2 data • Alzheimer's Disease • CNS Disorders • Huntington's Disease • Parkinson's Disease

A Study to Evaluate the Effects of SAGE-718 in Participants With Parkinson's Disease Cognitive Impairment (clinicaltrials.gov) - P2 | N=76 | Active, not recruiting | Sponsor: Sage Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease

Oxysterols in Central and Peripheral Synaptic Communication. (PubMed, Adv Exp Med Biol) - "Overall, oxysterols could be used as "molecular prototypes" for therapeutic approaches. Analogs of 24-hydroxycholesterol (SGE-301, SGE-550, SAGE718) can be used for correction of NMDA receptor hypofunction-related states, whereas inhibitors of cholesterol 24-hydroxylase, cholestane-3β,5α,6β-triol, and cholest-4-en-3-one oxime (olesoxime) can be utilized as potential anti-epileptic drugs and (or) protectors from excitotoxicity."

Journal • CNS Disorders • Epilepsy

Huntington's Disease Drug Development: A Phase 3 Pipeline Analysis. (PubMed, Pharmaceuticals (Basel)) - "Of the nine clinical trials that met these criteria, eight involved the following drugs: metformin, dextromethorphan/quinidine, deutetrabenazine, valbenazine, Cellavita HD, pridopidine, SAGE-718, and RO7234292 (RG6042). Of these drug treatments, four are already FDA approved. This systematic review provides a resource that summarizes the present therapies for treating this devastating condition that are currently in phase III clinical trials in the United States."

Journal • P3 data • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Huntington's Disease • Movement Disorders • Psychiatry

Mechanism and target engagement of SAGE-718, an NMDA receptor positive allosteric modulator (Neuroscience 2023) - "Together, these data indicate SAGE-718 can potentiate both in vitro and in vivo NMDAR-mediated currents and has potential to treat indications with NMDAR hypofunction. Further, the interaction of SAGE-718 with ketamine not only provides mechanistic insight into how SAGE-718 can potentiate NMDAR but also functions as a clinical translational biomarker."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • GRIN2A • GRIN2B