NBI-827104 / Idorsia, Neurocrine - LARVOL DELTA

Antiseizure potential of the triple T-type calcium channel blocker ACT-709478 (apinocaltamide) in rodent models. (PubMed, Epilepsia) - "Based on its efficacy profile in rodent models, ACT-709478 represents a promising drug candidate for the treatment of absence epilepsy such as childhood absence epilepsy or syndromes featuring SWDs. It could possibly also be beneficial for epileptic syndromes presenting with additional seizure types."

Journal • Preclinical • Absence Seizure Disorder • CNS Disorders • Epilepsy • CAV3

Steamboat 2: Extension Study to Evaluate NBI-827104 in Pediatric Participants With Epileptic Encephalopathy With Continuous Spike-and-Wave During Sleep (clinicaltrials.gov) - P2 | N=19 | Terminated | Sponsor: Neurocrine Biosciences | Active, not recruiting ➔ Terminated; Business decision

Trial termination • CNS Disorders • Epilepsy • Pediatrics

Steamboat 2: Extension Study to Evaluate NBI-827104 in Pediatric Participants With Epileptic Encephalopathy With Continuous Spike-and-Wave During Sleep (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: Neurocrine Biosciences | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Epilepsy • Pediatrics

Structural basis for human Cav3.2 inhibition by selective antagonists. (PubMed, Cell Res) - "ACT-709478 and TTA-A2 both place their cyclopropylphenyl-containing ends in the central cavity to directly obstruct ion flow, meanwhile extending their polar tails into the IV-I fenestration...Structure-guided mutational analysis identifies several key residues that determine the T-type preference of these drugs. The structures also suggest the role of an endogenous lipid in stabilizing drug binding in the central cavity."

Journal • CNS Disorders • Epilepsy • Pain • CAV3

An evaluation of NBI-827104 for essential tremor: results from a randomized, double-blind, placebo- controlled, dose-escalation, crossover study (MDS Congress 2023) - P2 | "NBI-827104 did not meet the primary or secondary efficacy endpoints. No statistically significant differences between treatment groups were observed using accelerometry and clinical scales."

Clinical • CNS Disorders • Essential Tremor

Steamboat 2: Extension Study to Evaluate NBI-827104 in Pediatric Subjects With Epileptic Encephalopathy With Continuous Spike-and-Wave During Sleep (clinicaltrials.gov) - P2 | N=24 | Enrolling by invitation | Sponsor: Neurocrine Biosciences | Trial completion date: Nov 2024 ➔ Feb 2025 | Trial primary completion date: Nov 2024 ➔ Feb 2025

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy • Pediatrics

Neurocrine Biosciences Provides Update on Phase 2 Study of NBI-827104 in Pediatric Patients with Epileptic Encephalopathy with Continuous Spike-and-Wave During Sleep (PRNewswire) - P2 | N=24 | STEAMBOAT (NCT04625101) | Sponsor: Neurocrine Biosciences | "Neurocrine Biosciences, Inc...announced that investigational NBI-827104 did not meet its primary endpoint in the Phase 2 STEAMBOAT™ study evaluating the efficacy, safety, tolerability and pharmacokinetics of NBI-827104 compared to placebo in pediatric patients with epileptic encephalopathy with continuous spike-and-wave during sleep (EE-CSWS). NBI-827104 was generally well tolerated."

P2 data • CNS Disorders • Epilepsy

Efficacy, Safety, Tolerability, and Pharmacokinetics of NBI-827104 in Pediatric Subjects With Epileptic Encephalopathy With Continuous Spike-and-Wave During Sleep (clinicaltrials.gov) - P2 | N=24 | Completed | Sponsor: Neurocrine Biosciences | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Epilepsy • Pediatrics

Steamboat 2: Extension Study to Evaluate NBI-827104 in Pediatric Subjects With Epileptic Encephalopathy With Continuous Spike-and-Wave During Sleep (clinicaltrials.gov) - P2 | N=24 | Enrolling by invitation | Sponsor: Neurocrine Biosciences | Not yet recruiting ➔ Enrolling by invitation | Trial completion date: Aug 2024 ➔ Nov 2024 | Trial primary completion date: Aug 2024 ➔ Nov 2024

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy • Pediatrics

Safety, Efficacy, and Tolerability of NBI-827104 for the Treatment of Essential Tremor (clinicaltrials.gov) - P2 | N=31 | Completed | Sponsor: Neurocrine Biosciences | Recruiting ➔ Completed

Trial completion • Essential Tremor • Movement Disorders

Efficacy, Safety, Tolerability, and Pharmacokinetics of NBI-827104 in Pediatric Subjects With Epileptic Encephalopathy With Continuous Spike-and-Wave During Sleep (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: Neurocrine Biosciences | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2022 ➔ Nov 2022 | Trial primary completion date: May 2022 ➔ Aug 2022

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy • Pediatrics

Idorsia announces financial results for the first quarter 2022 – first product launched, second in the starting blocks (GlobeNewswire) - "Neurocrine Biosciences has a global license to develop and commercialize ACT-709478 (NBI-827104), Idorsia's novel T-type calcium channel blocker. ACT-709478 is currently investigated in two Phase 2 studies for the treatment of a rare form of pediatric epilepsy and essential tremor."

Clinical • CNS Disorders • Epilepsy

Safety, Efficacy, and Tolerability of NBI-827104 for the Treatment of Essential Tremor (clinicaltrials.gov) - P2 | N=28 | Recruiting | Sponsor: Neurocrine Biosciences | Trial completion date: Mar 2022 ➔ Jun 2022

Trial completion date • Essential Tremor • Movement Disorders

Epilepsy: Expert opinion on emerging drugs in phase 2/3 clinical trials. (PubMed, Expert Opin Emerg Drugs) - "Novel mechanisms of action involve cholesterol degradation, mitochondrial pathways, anti-inflammation and neuro-regeneration. Earlier identification of genetic conditions through genetic testing will allow for earlier use of disease specific and disease-modifying therapies."

Journal • P2/3 data • CNS Disorders • Epilepsy • Immunology • Inflammation

Steamboat 2: Extension Study to Evaluate NBI-827104 in Pediatric Subjects With Epileptic Encephalopathy With Continuous Spike-and-Wave During Sleep (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: Neurocrine Biosciences

New P2 trial • CNS Disorders • Epilepsy • Pediatrics

A long-duration study to assess the safety and effectiveness of NBI-827104 in children with Epileptic Encephalopathy with Continuous Spike-and-Wave During Sleep. (clinicaltrialsregister.eu) - P2 | N=24 | Sponsor: Neurocrine Biosciences, Inc.

New P2 trial • CNS Disorders • Epilepsy • Pediatrics

Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets. (PubMed, Front Pain Res (Lausanne)) - "Despite this, peripheral voltage-gated cation channels retain their promise as therapeutic targets. The way forward may include (i) further structural refinement of K channel activators such as retigabine and ASP0819 to improve selectivity and limit toxicity; use or modification of Na channel blockers such as vixotrigine, PF-05089771, A803467, PF-01247324, VX-150 or arachnid toxins such as Tap1a; the use of Ca channel blockers such as TTA-P2, TTA-A2, Z 944, ACT709478, and CNCB-2; (ii) improving methods for assessing "pain" as opposed to nociception in rodent models; (iii) recognizing sex differences in pain etiology; (iv) tailoring of therapeutic approaches to meet the symptoms and etiology of pain in individual patients via quantitative sensory testing and other personalized medicine approaches; (v) targeting genetic and biochemical mechanisms controlling channel expression using anti-NGF antibodies such as tanezumab or re-purposed drugs such as vorinostat, a..."

Journal • Review • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lymphoma • Neuralgia • Oncology • Pain • Rheumatoid Arthritis • Rheumatology • T Cell Non-Hodgkin Lymphoma • TAP1

Efficacy, Safety, Tolerability, and Pharmacokinetics of NBI-827104 in Pediatric Subjects With Epileptic Encephalopathy With Continuous Spike-and-Wave During Sleep (clinicaltrials.gov) - P2; N=24; Recruiting; Sponsor: Neurocrine Biosciences; Trial completion date: Jan 2022 ➔ Jul 2022; Trial primary completion date: Dec 2021 ➔ May 2022

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy • Pediatrics

Neurocrine Biosciences Provides Preliminary Fourth Quarter and Full-Year 2021 Net Product Sales Results and Future Program Milestones (PRNewswire) - "Phase 2 Data Readouts for NBI-827104, a Novel T-Type Calcium Channel Blocker, in Essential Tremor and in Epileptic Encephalopathy with Continuous Spike and Wave During Sleep in 2022...Essential Tremor; Top-Line Phase 2 Data in Mid-2022...Rare Pediatric Epilepsy: CSWS; Top-Line Phase 2 Data in 2H 2022."

P2 data • CNS Disorders • Epilepsy • Essential Tremor

Neurocrine Biosciences Reports First Quarter 2021 Financial Results (PRNewswire) - "...the Company announced that investigational drug luvadaxistat (NBI-1065844/TAK-831) did not meet its primary endpoint in the Phase II INTERACT study...The Company plans to initiate a Phase II study for the treatment of cognitive impairment associated with schizophrenia (CIAS) by the end of 2021...NBI-827104...Essential Tremor...Enrolling Phase II Study"

Enrollment status • New P2 trial • CNS Disorders • Schizophrenia

Safety, Efficacy, and Tolerability of NBI-827104 for the Treatment of Essential Tremor (clinicaltrials.gov) - P2; N=28; Recruiting; Sponsor: Neurocrine Biosciences

Clinical • New P2 trial • Essential Tremor • Movement Disorders

Safety and efficacy of an investigational drug for essential tremor (clinicaltrialsregister.eu) - P2; N=28; Ongoing; Sponsor: Neurocrine Biosciences

Clinical • New P2 trial • Essential Tremor • Movement Disorders

Efficacy, Safety, Tolerability, and Pharmacokinetics of NBI-827104 in Pediatric Subjects With Epileptic Encephalopathy With Continuous Spike-and-Wave During Sleep (clinicaltrials.gov) - P2; N=24; Recruiting; Sponsor: Neurocrine Biosciences; Not yet recruiting ➔ Recruiting; Initiation date: Nov 2020 ➔ Mar 2021

Clinical • Enrollment open • Trial initiation date • CNS Disorders • Epilepsy • Pediatrics

A study to assess the efficacy, safety, tolerability and pharmacokinetics of NBI-827104 in pediatric subjects with Epileptic Encephalopathy with Continuous Spike-and-Wave During Sleep (clinicaltrialsregister.eu) - P2; N=24; Sponsor: Neurocrine Biosciences, Inc.

Clinical • New P2 trial • CNS Disorders • Epilepsy • Pediatrics

Neurocrine Biosciences Provides Preliminary Fourth Quarter and Full-Year 2020 Net Product Sales Results and 2021 Program Milestones (PRNewswire) - "NBI-827104...Rare Pediatric Epilepsy, Epileptic Encephalopathy with Continuous Spike and Wave During Sleep, Neurological Indication: Continue Phase II Enrollment. NBI-921352: Focal Onset Seizure in Adults, Rare Pediatric Epilepsy: SCN8A-DEE: Initiate Phase II, Ongoing Dialogue with FDA. NBIb-1817: Gene Therapy for Parkinson's Disease: Determine Regulatory Path with FDA."

Enrollment status • FDA event • New P2 trial • CNS Disorders • Epilepsy • Parkinson's Disease