SAGE-324 / Sage Therapeutics - LARVOL DELTA

Sage Therapeutics Announces Fourth Quarter and Full Year 2024 Financial Results and Highlights Pipeline and Business Updates (Businesswire) - "SAGE-324: The Company is evaluating potential indications, including seizures in developmental and epileptic encephalopathies (DEEs), and expects to provide an update on next steps, if any, in mid-2025....Collaboration revenue from sales of ZURZUVAE was $11.4 million in the fourth quarter of 2024 compared to $0.8 million for the same period in 2023. For the year ended December 31, 2024, the first full year of sales, collaboration revenue from sales of ZURZUVAE was $36.1 million. Reported collaboration revenue is 50% of the net revenues Biogen records for ZURZUVAE in the U.S. Net revenue from sales of ZULRESSO was $0.4 million in the fourth quarter of 2024 compared to $2.0 million in the same period of 2023."

Clinical • Commercial • CNS Disorders • Epilepsy • Postpartum Depression

A Study to Evaluate the Long-term Safety and Tolerability of SAGE-324 in Participants With Essential Tremor (clinicaltrials.gov) - P2/3 | N=97 | Terminated | Sponsor: Sage Therapeutics | Trial completion date: Sep 2027 ➔ Sep 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2027 ➔ Sep 2024; Internal company decision

Trial completion date • Trial primary completion date • Trial termination • Essential Tremor • Movement Disorders

SAGE-324/BIIB124, an investigational GABAA receptor PAM, for treatment of essential tremor (MDS Congress 2024) - P2 | "Eligibility criteria included: ages 18−80 years; ET diagnosis​ (isolated bilateral UL action tremor ≥3 years with/without tremor in other locations); no other relevant neurological signs; The Essential Tremor Rating Assessment Scale (TETRAS)-Performance Scale (PS) Subscale Item 4 (UL) score ≥12 (≥6 dominant UL) at screening/baseline; at screening TETRAS Activities of Daily Living (ADL) Subscale score ≥20; willingness to discontinue ET medications except propranolol (≤320 mg/day). KINETIC2 was designed to evaluate SAGE-324/BIIB124 dose response on clinically relevant endpoints and safety/tolerability. Enrollment is complete and results from KINETIC2 will be presented. ."

CNS Disorders • Essential Tremor • DERL1

A Study to Evaluate the Long-term Safety and Tolerability of SAGE-324 in Participants With Essential Tremor (clinicaltrials.gov) - P2/3 | N=97 | Active, not recruiting | Sponsor: Sage Therapeutics | Recruiting ➔ Active, not recruiting | N=750 ➔ 97

Enrollment change • Enrollment closed • Essential Tremor • Movement Disorders

Sage Therapeutics and Biogen Announce Topline Results from Phase 2 KINETIC 2 Study of SAGE-324 (BIIB124) for the Treatment of Essential Tremor (Businesswire) - P2 | N=147 | NCT05173012 | Sponsor: Sage Therapeutics | "Sage Therapeutics, Inc...and Biogen Inc...announced topline results from the Phase 2 KINETIC 2 dose-range study of the oral investigational drug SAGE-324 (BIIB124) as a potential treatment in essential tremor (ET). The KINETIC 2 Study did not demonstrate a statistically significant dose-response relationship in change from baseline to Day 91 based on the primary endpoint, The Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale (PS) Item 4 (upper limb) total score, in participants with ET. In addition, there were no statistically significant differences demonstrated for any dose of SAGE-324 versus placebo in the change from baseline to Day 91 on the TETRAS PS Item 4 Total Score or the TETRAS Activities of Daily Living (ADL) Composite Score."

P2 data • CNS Disorders • Essential Tremor

Study to Evaluate SAGE-324 in Participants With Essential Tremor (clinicaltrials.gov) - P2 | N=147 | Completed | Sponsor: Sage Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Essential Tremor • Movement Disorders

Study to Evaluate SAGE-324 in Participants With Essential Tremor (clinicaltrials.gov) - P2 | N=160 | Active, not recruiting | Sponsor: Sage Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Essential Tremor • Movement Disorders

A Randomized Phase 2 KINETIC Trial Evaluating SAGE-324/BIIB124 in Individuals with Essential Tremor. (PubMed, Mov Disord) - P2 | "These results support further development of SAGE-324/BIIB124 for potential ET treatment."

Journal • P2 data • CNS Disorders • Essential Tremor • Fatigue • Movement Disorders • Otorhinolaryngology • Parkinson's Disease

Sage Therapeutics Implements Strategic Reorganization to Support Plans for ZURZUVAE Commercial Launch and Pipeline Advancement (Businesswire) - "Sage Therapeutics, Inc...announced plans to reorganize its business operations and pipeline priorities to support goals for long-term business growth, including the planned commercial launch of ZURZUVAE for women with postpartum depression (PPD) in late 2023....Refine pipeline development efforts to advance SAGE-718 and SAGE-324, as well as pause certain earlier-stage programs, with the goal of making evidence-driven investments..."

Launch • Pipeline update • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Depression • Genetic Disorders • Huntington's Disease • Parkinson's Disease • Postpartum Depression

KINETIC 2: An ongoing phase 2b, randomized, dose-response study of SAGE-324/BIIB124 for the treatment of essential tremor (MDS Congress 2023) - P2 | "KINETIC 2 was designed to evaluate SAGE-324 dose response on clinically relevant endpoints and safety in patients with ET. Enrollment is ongoing, and the results of this trial will inform future SAGE-324 clinical development."

Clinical • P2b data • CNS Disorders • Essential Tremor

A phase 2b, randomized, dose-response study of SAGE-324/BIIB124 for the treatment of essential tremor: KINETIC 2 trial in progress (IAPRD 2023) - P2 | N=160 | KINETIC 2 (NCT05173012) | Sponsor: Sage Therapeutics | "The phase 2b KINETIC 2 trial was designed to evaluate SAGE-324 dose-response on clinically relevant endpoints and safety. Enrollment is ongoing, and the results will inform future SAGE-324 clinical development."

P2 data

A Study to Evaluate the Long-term Safety and Tolerability of SAGE-324 in Participants With Essential Tremor (clinicaltrials.gov) - P2/3 | N=750 | Recruiting | Sponsor: Sage Therapeutics | Phase classification: P2 ➔ P2/3

Phase classification • Essential Tremor • Movement Disorders

Sage Therapeutics Announces Fourth Quarter and Full Year 2022 Financial Results and Highlights Pipeline and Business Progress (Sage Therapeutics Press Release) - "R&D Expenses: Research and development expenses were $89.3 million, including $4.9 million of non-cash stock-based compensation expense, in the fourth quarter of 2022 compared to $75.4 million...For the year ended December 31, 2022, R&D expenses were $326.2 million, including $25.9 million of non-cash stock-based compensation expense...For the year, the increase in R&D expenses was primarily due to increased spending on SAGE-324 and Sage’s wholly owned pipeline, including SAGE-718 and other programs....The Company anticipates R&D and SG&A spending to increase as it prepares for the potential launch of zuranolone and advances planned and ongoing studies for SAGE-718 and SAGE-324.​"

Commercial • Alzheimer's Disease • CNS Disorders • Epilepsy • Parkinson's Disease

Study to Evaluate SAGE-324 in Participants With Essential Tremors (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Sage Therapeutics | Trial completion date: Jun 2023 ➔ Mar 2024 | Trial primary completion date: Jun 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Essential Tremor • Movement Disorders

A phase 2b, randomized, dose-response study of SAGE-324/BIIB124 for the treatment of essential tremor: KINETIC 2 trial in progress (MDS Congress 2022) - P2 | "The phase 2b KINETIC 2 trial was designed to evaluate SAGE-324 dose response on clinically relevant endpoints, including ADL, and safety. Enrollment is ongoing, and the results of this trial will inform the clinical development of SAGE-324."

Clinical • P2b data • CNS Disorders • Essential Tremor

Sage Therapeutics Announces Second Quarter 2022 Financial Results and Highlights Pipeline and Business Progress (Sage Therapeutics Press Release) - "Research and development expenses were $77.3 million, including $6.5 million of non-cash stock-based compensation expense, in the second quarter of 2022 compared to $66.2 million, including $13.5 million of non-cash stock-based compensation expense, for the same period in 2021. The increase in R&D expenses was primarily due to increased spending on SAGE-324 and Sage’s wholly owned pipeline, including SAGE-718 and other programs..."

Commercial • Alzheimer's Disease • CNS Disorders • Huntington's Disease • Parkinson's Disease

A Study to Evaluate the Long-term Safety and Tolerability of SAGE-324 in Participants With Essential Tremor (clinicaltrials.gov) - P2 | N=750 | Recruiting | Sponsor: Sage Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Essential Tremor • Movement Disorders

A Study to Evaluate the Long-term Safety and Tolerability of SAGE-324 in Participants With Essential Tremor (clinicaltrials.gov) - P2 | N=750 | Not yet recruiting | Sponsor: Sage Therapeutics

New P2 trial • Essential Tremor • Movement Disorders

Study to Evaluate SAGE-324 in Participants With Essential Tremors (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Sage Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Essential Tremor • Movement Disorders

The imidazodiazepine, KRM-II-81: An example of a newly emerging generation of GABAkines for neurological and psychiatric disorders. (PubMed, Pharmacol Biochem Behav) - "Recently, however, there has been a resurgence of efforts to bring GABAkines to patients, the FDA approval of the neuroactive steroid brexanolone for post-partum depression in 2019 being the first. Other neuroactive steroids are in various stages of clinical development (ganaxolone, zuranolone, LYT-300, Sage-324, PRAX 114, and ETX-155). These GABAkines and non-steroid compounds (GRX-917, a TSPO binding site ligand), darigabat (CVL-865), an α2/3/5-preferring GABAkine, SAN711, an α3-preferring GABAkine, and the α2/3-preferring GABAkine, KRM-II-81, bring new therapeutic promise to this highly utilized medicinal target in neurology and psychiatry...KRM-II-81 also produces anxiolytic- and antidepressant-like effects in rodent models. Other key features of the pharmacology of this compound are its low sedation rate, lack of tolerance development, and the ability to prevent the development of seizure sensitization."

Journal • Review • Anesthesia • CNS Disorders • Depression • Epilepsy • Mental Retardation • Neuralgia • Pain • Postpartum Depression • Psychiatry • Vascular Neurology

Study to Evaluate SAGE-324 in Participants With Essential Tremors (clinicaltrials.gov) - P2; N=160; Not yet recruiting; Sponsor: Sage Therapeutics

Clinical • New P2 trial • Essential Tremor • Movement Disorders

Sage Therapeutics’ Third Annual FutureCast Showcases Data from All Three Brain Health Franchises (Businesswire) - "Now enrolling patients in KINETIC 2, a Phase 2b dose-ranging study evaluating SAGE-324 in essential tremor...SAGE-324: Patient-led Drug Development to Address the Unmet Need in Essential Tremor....Today, Sage Therapeutics, Inc....will host its third annual 'FutureCast: An R&D Portfolio Review' to showcase the Company’s research and development strategy, and clinical progress in its depression, neurology, and neuropsychiatry franchise programs."

Enrollment status • Review • Alzheimer's Disease • CNS Disorders • Essential Tremor • Parkinson's Disease

Sage Therapeutics to Host Sage FutureCast Webcast (Businesswire) - "Sage Therapeutics, Inc...announced that it will host Sage FutureCast: An R&D and Portfolio Review on Tuesday, December 14 from 8:00 a.m. to 10:00 a.m. ET. Sage FutureCast will discuss the Company’s research and development strategy, and clinical progress in programs throughout the depression, neurology, and neuropsychiatry franchises including zuranolone, SAGE-324 and SAGE-718, respectively."

Clinical • CNS Disorders • Epilepsy • Essential Tremor

GABAkines - Advances in the discovery, development, and commercialization of positive allosteric modulators of GABA receptors. (PubMed, Pharmacol Ther) - "Traditional GABAkines like diazepam have safety and tolerability concerns that include sedation, motor-impairment, respiratory depression, tolerance and dependence...The compounds that are presently being developed and commercialized include several neuroactive steroids (an allopregnanolone formulation (brexanolone), an allopregnanolone prodrug (LYT-300), Sage-324, zuranolone, and ganaxolone), the α2/3-preferring GABAkine, KRM-II-81, and the α2/3/5-preferring GABAkine PF-06372865 (darigabat)...Medicinal chemistry efforts are also ongoing to identify novel and improved GABAkines. The data document gaps in our understanding of the molecular pharmacology of GABAkines that drive differential pharmacological profiles, but emphasize advancements in the ability to successfully utilize GABA receptor potentiation for therapeutic gain in neurology and psychiatry."

Journal • Review • Anesthesia • CNS Disorders • Depression • Epilepsy • Mood Disorders • Movement Disorders • Pain • Postpartum Depression • Psychiatry

Sage Therapeutics Announces Third Quarter 2021 Financial Results and Highlights Pipeline and Business Progress (BioSpace) - "Late 2021: Phase 2 Study in ET: Sage and Biogen anticipate initiating a placebo-controlled Phase 2 dose-ranging study in SAGE-324 for ET designed to optimize the dose and frequency in late 2021."

New P2 trial • CNS Disorders • Essential Tremor