ganaxolone IV / Marinus, Tenacia Biotech, Ligand - LARVOL DELTA

Intravenous Ganaxolone in Refractory Status Epilepticus: Results from the Phase 3 double-blind, randomized, placebo-controlled RAISE Trial (AES 2024) - P2, P3 | "IV ganaxolone produced rapid SE cessation (median 4 min) but was not associated with statistically significant difference in escalation to IVA despite a reduction in EEG seizure burden. Avoiding progression to IVA was confounded by intercurrent clinical and treatment factors, and therefore may not be a valid proxy for SE cessation. Escalation of care with any SE treatment and reduction in EEG seizure burden may represent potential endpoints for future trials."

Clinical • P3 data • Anesthesia • CNS Disorders • Epilepsy • Hypotension

Efficacy and Safety of Intravenous Ganaxolone for Treatment of Refractory Status Epilepticus: Results from the Phase 3, Double-Blind, Randomized, Placebo-Controlled RAISE Trial (NCS 2024) - No abstract available

Clinical • Late-breaking abstract • P3 data • Epilepsy

RAISE: Randomized Therapy In Status Epilepticus (clinicaltrials.gov) - P3 | N=124 | Completed | Sponsor: Marinus Pharmaceuticals | Active, not recruiting ➔ Completed | Trial completion date: Nov 2024 ➔ Apr 2024 | Trial primary completion date: Nov 2024 ➔ Mar 2024

Trial completion • Trial completion date • Trial primary completion date • Epilepsy

Super Refractory Status Epilepticus Improved After Emergency Use of Ganaxolone: Case Report. (PubMed, Neurohospitalist) - "Emergency use authorization was obtained for intravenous ganaxolone, a neuroactive steroid that is a potent modulator of both synaptic and extrasynaptic GABAA receptors. Following administration of intravenous ganaxolone according to a novel dosing paradigm, the patient showed sustained clinical and electrographic improvement."

Journal • CNS Disorders • Epilepsy • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

RAISE: Randomized Therapy In Status Epilepticus (clinicaltrials.gov) - P3 | N=124 | Active, not recruiting | Sponsor: Marinus Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2023 ➔ Nov 2024 | Trial primary completion date: Oct 2023 ➔ Nov 2024

Enrollment closed • Trial completion date • Trial primary completion date • Epilepsy

To Evaluate the Efficacy, Safety, and Tolerability of Intravenous Ganaxolone Added to Standard of Care in Refractory Status Epilepticus (RSE) (clinicaltrials.gov) - P3 | N=0 | Withdrawn | Sponsor: Marinus Pharmaceuticals | N=70 ➔ 0 | Trial completion date: Nov 2025 ➔ Aug 2024 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Nov 2025 ➔ Aug 2024

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Epilepsy

Safety and Efficacy Study of IV Ganaxolone as Adjuvant Therapy for Established Status Epilepticus (ESE) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Marinus Pharmaceuticals | N=120 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Epilepsy

To Evaluate the Efficacy, Safety, and Tolerability of Intravenous Ganaxolone Added to Standard of Care in Refractory Status Epilepticus (RSE) (clinicaltrials.gov) - P3 | N=70 | Not yet recruiting | Sponsor: Marinus Pharmaceuticals | Initiation date: Sep 2023 ➔ Feb 2024

Trial initiation date • Epilepsy

Intravenous Ganaxolone: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability in Healthy Adults. (PubMed, Clin Pharmacol Drug Dev) - "No effects on systemic hemodynamics or respiratory functions were reported. Overall, ganaxolone was generally well tolerated at the doses studied and demonstrated pharmacokinetic and pharmacodynamic properties suitable to treat SE."

Journal • PK/PD data • Anesthesia • CNS Disorders • Epilepsy • Genetic Disorders

Intravenous Ganaxolone Attenuates Sarin Nerve Agent Induced Seizures (AES 2023) - "The Biomedical Advanced Research and Development Authority (BARDA), within the Administration for Strategic Preparedness and Response in the US Department of Health and Human Services (HHS), is partnering with Marinus to develop GNX as a treatment for RSE following organophosphate nerve agent exposure in subjects that are not responsive to agents FDA-approved for nerve agent induced seizures (Seizalam® midazolam hydrochloride) or other benzodiazepines. GNX administration attenuated RSE in Sarin exposed rats in a dose-dependent manner and established a PK/PD relationship between GNX plasma levels and the anti-seizure response. GNX was also shown to prevent Sarin-mediated neuronal loss in various brain regions. These studies support the ongoing development of GNX as a medical countermeasure for the treatment of individuals exposed to organophosphate nerve agents."

CNS Disorders • Epilepsy • Genetic Disorders

Intravenous Ganaxolone in Non-Intubated Patients with Refractory Status Epilepticus: Subanalysis of an Open-label, Dose-finding, Phase 2 Trial (NCS 2023) - No abstract available

Clinical • P2 data • Epilepsy

Intravenous Ganaxolone in Non-Intubated Patients with Refractory Status Epilepticus: Subanalysis of an Open-label, Dose-finding, Phase 2 Trial (NCS 2023) - No abstract available

Clinical • P2 data • Epilepsy

Marinus Pharmaceuticals Announces New Method of Use Patent Granted for IV Ganaxolone by USPTO in Status Epilepticus (Businesswire) - "Marinus Pharmaceuticals...today announced that the United States Patent and Trademark Office (USPTO) has granted a new method of use patent for intravenous (IV) ganaxolone in the treatment of status epilepticus (SE), expiring in 2040. The USPTO issued U.S. Patent No. 11,679,117, covering the clinical dosing regimen administering ganaxolone for SE patients, including those with refractory and super refractory status epilepticus."

Patent • CNS Disorders • Epilepsy

Safety and Efficacy Study of IV Ganaxolone as Adjuvant Therapy for Established Status Epilepticus (ESE) (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Marinus Pharmaceuticals | Not yet recruiting ➔ Recruiting | Initiation date: Jan 2026 ➔ Apr 2023

Enrollment open • Trial initiation date • Epilepsy

To Evaluate the Efficacy, Safety, and Tolerability of Intravenous Ganaxolone Added to Standard of Care in Refractory Status Epilepticus (RSE) (clinicaltrials.gov) - P3 | N=70 | Not yet recruiting | Sponsor: Marinus Pharmaceuticals

New P3 trial • Epilepsy

Safety and Efficacy Study of IV Ganaxolone as Adjuvant Therapy for Established Status Epilepticus (ESE) (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Marinus Pharmaceuticals

New P2 trial • Epilepsy

PHARMACOKINETICS, PHARMACODYNAMICS, AND SAFETY OF INTRAVENOUS GANAXOLONE IN HEALTHY ADULT VOLUNTEERS (SCCM 2023) - "The effects of IV GNX on PK and PD correlated with dose and administration duration. Following IV bolus, GNX was detected in plasma within 5min with onset of PD effects within 15min, with rapid clearance from plasma and reversal of PD effects. GNX was generally well tolerated at the doses studied."

Clinical • PK/PD data • Anesthesia • Epilepsy

Marinus Pharmaceuticals, Inc. (NASDAQ:MRNS) Q3 2022 Earnings Call Transcript (Yahoo Finance) - "Looking to the future of the RAISE study...the trial can enroll patients ages 12 years and over. We will shortly be submitting a request to the FDA with supporting data that potentially allowed us to include younger patients. Given the higher incidence of status epilepticus in children under 12, this change could expand the pool of eligible patients and further support timely study enrollment. As previously disclosed, we have the option for an independent data monitoring committee to conduct an interim analysis when two-thirds of participants have completed the study, approximately 82 patients."

Clinical • CNS Disorders • Epilepsy

Marinus Pharmaceuticals Announces Presentations and Investor Event at American Epilepsy Society 2022 Annual Meeting (Businesswire) - "Marinus Pharmaceuticals...today announced that ganaxolone data from three abstracts, including one late-breaking abstract, will be presented at the upcoming 2022 American Epilepsy Society (AES) Annual Meeting, which will be held December 2-6, 2022, in Nashville, TN."

Clinical data • Late-breaking abstract • CNS Disorders • Epilepsy

Pharmacokinetic, Pharmacodynamics, and Safety Study of Intravenous Ganaxolone in Healthy Adult Volunteers (AES 2022) - "Data with adjusted r-square < 0.8 were excluded. Quantitative electroencephalography (qEEG) measures, bispectral index (BIS), modified observers' assessment of alertness and sedation (MOAA/S), plasma concentrations, and safety data were collected."

Clinical • PK/PD data • Anesthesia • CNS Disorders • Epilepsy

Marinus Pharma, Tenacia Biotech Ink Ganaxolone Agreement In China (Yahoo Finance) - "Marinus Pharmaceuticals Inc...has entered into a collaboration and supply agreement with Tenacia Biotechnology (Shanghai) Co., Ltd., a China-based biotechnology company focused on the development of treatments for central nervous system (CNS) disorders. Under the terms of the agreement, Tenacia will receive exclusive rights to develop and commercialize certain formulations of ganaxolone in Mainland China, Hong Kong, Macau, and Taiwan, including the current oral and intravenous (IV) dose formulations and a right of first negotiation for a future next-generation formulation or prodrug."

Licensing / partnership • CNS Disorders • Epilepsy

Marinus Pharmaceuticals Provides Business Update and Reports Third Quarter 2022 Financial Results (Businesswire) - "Actively recruiting Phase 3 clinical trials in refractory status epilepticus and tuberous sclerosis complex; data continues to be expected 2H 2023 and Q1 2024, respectively...Phase 2 RESET trial in established status epilepticus (ESE) site activations underway and expected to begin U.S. enrollment by year end...Net product revenues of $0.56 million were recorded for each of the three and nine months ended September 30, 2022 as a result of the commercial launch of ZTALMY in late July 2022. No net products revenues were recorded in periods prior to the launch."

Enrollment status • P3 data: top line • CNS Disorders • Epilepsy

RAISE: RAndomized Therapy In Status Epilepticus (clinicaltrials.gov) - P3 | N=124 | Recruiting | Sponsor: Marinus Pharmaceuticals | Trial completion date: Mar 2022 ➔ Oct 2023 | Trial primary completion date: Jan 2022 ➔ Oct 2023

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

Intravenous Ganaxolone for the Treatment of Refractory Status Epilepticus: Results from an Open-Label, Dose-Finding, Phase 2 Trial. (PubMed, Epilepsia) - "IV ganaxolone achieved rapid and durable seizure control in patients with refractory status epilepticus, and showed, acceptable safety and tolerability."

Journal • P2 data • Aesthetic Medicine • Anesthesia • CNS Disorders • Critical care • Epilepsy

Marinus Pharmaceuticals Expands Enrollment Criteria to Support Recruitment in Phase 3 RAISE Trial in Refractory Status Epilepticus (Businesswire) - "Marinus Pharmaceuticals, Inc...announced that it has amended the protocol for its Phase 3 RAISE trial in refractory status epilepticus (RSE) to expand eligibility criteria, support patient recruitment and drive enrollment efficiencies at clinical sites....Marinus expects that the vast majority of sites will adopt these protocol updates by the middle of the third quarter of 2022....To further support recruitment and enrollment, Marinus expects to initiate site activations in Canada in the third quarter of 2022 targeting 10 new sites and is evaluating further expansion into Israel and Australia. The company is targeting 65-75 sites globally and continues to expect topline data in the second half of 2023."

Clinical protocol • P3 data: top line • CNS Disorders • Epilepsy