Double-blind, Randomized, Placebo-controlled Trial of Adjunctive Ganaxolone in the Treatment of Seizures Associated With Genetically Confirmed Cyclin-dependent Kinase-like 5 (CDKL5) Deficiency Disorder (CDD) in Pediatric Patients From 6 Months to Less Than 2 Years of Age.

This study will assess the efficacy, safety, and tolerability of ganaxolone (GNX) compared with placebo (PBO) as adjunctive therapy to the participant's standard anti-epileptic medication for the treatment of seizures in pediatric patients from 6 months to less than 2 years old with genetically confirmed CDD during a 12-week, DB phase. Pharmacokinetic (PK) assessments and population PK analyses will also be performed during this time. The DB phase will be followed by an optional long-term OL phase at which time all participants will receive GNX as an adjunct to their standard anti-seizure medication. Efficacy, safety and tolerability, and PK assessments will continue to be performed.

Start Date01 Dec 2024

Sponsor / Collaborator

Marinus Pharmaceuticals, Inc.

NCT05814523

/ WithdrawnPhase 3

A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Intravenous Ganaxolone Added to Standard of Care in Refractory Status Epilepticus

This is a multicenter, double-blind, randomized, placebo-controlled study that will evaluate the efficacy, safety, and tolerability of intravenous (IV) ganaxolone versus placebo co-administered with IV antiepileptic drug (AED) according to standard of care for the treatment of RSE. Approximately 70 participants will be randomized in a 1:1 ratio to receive ganaxolone IV solution or placebo IV solution along with standard of care (SOC) IV AED.

Start Date01 Mar 2024

Sponsor / Collaborator

Marinus Pharmaceuticals, Inc.

CTR20233334

/ RecruitingPhase 3

一项在结节性硬化症（TSC）相关癫痫儿童和成人患者中评价Ganaxolone（GNX）添加治疗的开放标签III期研究（TrustTSC OLE）

[Translation] An Open-Label Phase III Study Evaluating Ganaxolone (GNX) as Add-On Therapy in Children and Adults with Tuberous Sclerosis Complex (TSC)-Related Epilepsy (TrustTSC OLE)

主要目的：评估GNX作为儿童和成人TSC相关癫痫发作的添加治疗的长期安全性和耐受性。

[Translation]

Primary objective: To evaluate the long-term safety and tolerability of GNX as an add-on treatment for TSC-related seizures in children and adults.

Start Date05 Dec 2023

Sponsor / Collaborator

Altasciences Co., Inc.

[+2]

100 Clinical Results associated with Ganaxolone

100 Translational Medicine associated with Ganaxolone

100 Patents (Medical) associated with Ganaxolone

196

Literatures (Medical) associated with Ganaxolone

01 Jan 2025·Frontiers in Neuroendocrinology

Neurosteroid replacement approaches for improving outcomes after compromised pregnancies and preterm birth

Review

Author: Moloney, Roisin A ; Shaw, Julia C ; Hirst, Jonathan J ; Pavy, Carlton ; Palliser, Hannah K

The levels of the key neurosteroid of pregnancy, allopregnanolone, are very high in the fetal and maternal brain compared to after birth. These levels are maintained by the placenta which forms a placental connection to fetal brain development. Maternal stresses depress placental synthesis resulting in a fall in allopregnanolone levels leading to deficits in myelination that continue into childhood. This contributes to an increased incidence of behavioural disorders. Supplementing neurosteroid action with allopregnanolone analogues or raising endogenous production with mitochondrial translocator protein (TSPO) ligands reverses these deficits. Preterm birth leads to an early dramatic loss of neurosteroid support for brain development leading to marked deficits in myelination and susceptibility to hypoxic-ischaemic injury. Postnatal treatment with the allopregnanolone analogue ganaxolone improves myelination and reduces hyperactive behaviour. TSPO ligands such as emapunil have been shown to improve oligodendrocyte maturation. These findings support the use of allopregnanolone supplementation approaches after pregnancy compromises to improve outcome.

01 Nov 2024·Developmental Psychobiology

Ganaxolone Therapy After Preterm Birth Restores Cerebellar Oligodendrocyte Maturation and Myelination in Guinea Pigs

Article

Author: Berry, Mary J. ; Dyson, Rebecca M. ; Sixtus, Ryan P. ; Moloney, Roisin A. ; Palliser, Hannah K. ; Shaw, Julia C. ; Pavy, Carlton L. ; Hirst, Jonathan J.

ABSTRACTThe postnatal environment is challenging for the preterm neonate with exposure to hypoxic and excitotoxic events, amplified by premature loss of placentally derived neurosteroids. Between preterm birth and term equivalent age (TEA), cerebellar development continues despite these challenges. We hypothesize that neurosteroid replacement therapy during this time will support optimal cerebellar development. Guinea pig sows delivered at term (∼69 days gestation) or were induced to deliver preterm (∼62 days), with preterm pups receiving ganaxolone or vehicle until TEA. Postnatal assessments comprised salivary cortisol (corrected postnatal age [CPA] 0, 7, 38), behavioral analysis (CPA7, 38), and tissue collection (CPA0 and CPA40). Neurodevelopmental markers (MBP, Olig2, and NeuN) were assessed in the cerebellum by immunohistochemistry, whereas RT‐PCR was utilized to investigate key inhibitory/excitatory pathways and oligodendrocyte lineage markers. Following preterm birth, there was evidence of a hyperactive phenotype, increased salivary cortisol concentrations, and impaired myelination and oligodendrocyte maturation at the protein level. mRNA expressions of key inhibitory/excitatory pathways and myelin stability were also altered following preterm birth. Importantly, we showed that neurosteroid replacement therapy returns cerebellar development and behavior toward a term‐like phenotype. Therefore, ganaxolone may reduce the vulnerability of the cerebellum to postnatal challenges arising from preterm birth.

01 Nov 2024·Neuroscience Letters

Neurosteroids foster sedation by engaging tonic GABAA-Rs within the mesopontine tegmental anesthesia area (MPTA)

Article

Author: Baron, Mark ; Devor, Marshall

Neurosteroids are endogenous molecules with anxiolytic, anticonvulsant, sleep-promoting and sedative effects. They are biosynthesized de novo within the brain, among other tissues, and are thought to act primarily as positive allosteric modulators of high-affinity extrasynaptic GABA_Aδ-receptors. The location of action of neurosteroids in the brain, however, remains unknown. We have demonstrated that GABAergic anesthetics act within the brainstem mesopontine tegmental anesthesia area (MPTA) to induce and maintain anesthetic loss-of-consciousness. Here we asked whether endogenous and synthetic neurosteroids might also act in the MPTA to induce their suppressive effects. Direct exposure of the MPTA to the endogenous neurosteroids pregnenolone and progesterone, their metabolites testosterone, allopregnanolone and 3α5α-THDOC, and the synthetic neurosteroids ganaxolone and alphaxalone, was found to be pro-anesthetic. Although we cannot rule out additional sites of action, results of this study suggest that the suppressive effects of neurosteroids are due, at least in part, to actions within the MPTA, presumably by recruitment of dedicated neuronal circuitry. This undermines the usual presumption that neurosteroids, like other sedatives, endogenous somnogens and anesthetics, act by nonspecific global distribution.

124

News (Medical) associated with Ganaxolone

03 Jan 2025

·www.globenewswire.com

Orion and Marinus terminate agreement for ganaxolone in Europe

Orion Corporation (“Orion”) and Marinus Pharmaceuticals, Inc. (“Marinus”) have decided to mutually terminate their European wide marketing and distribution agreement for ganaxolone. Marinus regains ganaxolone’s commercial rights in Europe where the compound is approved for the adjunctive treatment of epileptic seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients two to 17 years of age. CDD is a serious and rare genetic disorder. Orion suspends all ganaxolone-related activities in Europe, including the ongoing preparations to launch the product. Based on Orion’s strategic choice to focus on oncology and pain in its innovative business, Orion deems that returning the European rights back to Marinus provides the best option for finding a solution to make the product globally available to the patients who need it. In connection with the termination of the agreement, Marinus pays Orion EUR 1.5 million in first half of 2025 for regaining the commercial rights of ganaxolone in Europe. In 2021, Orion paid Marinus EUR 25 million for the rights. Following the termination of the agreement, Orion will make a write-down of EUR 23.5 million in Q4 2024. Orion is a globally operating Finnish pharmaceutical company – a builder of well-being for over a hundred years. We develop, manufacture and market human and veterinary pharmaceuticals and active pharmaceutical ingredients. Orion has an extensive portfolio of proprietary and generic medicines and consumer health products. The core therapy areas of our pharmaceutical R&D are oncology and pain. Proprietary products developed by Orion are used to treat cancer, neurological diseases and respiratory diseases, among others. Orion's net sales in 2023 amounted to EUR 1,190 million and the company had about 3,600 employees at the end of the year. Orion's A and B shares are listed on Nasdaq Helsinki. The content above comes from the network. if any infringement, please contact us to modify.

License out/inDrug Approval

31 Dec 2024

·www.pharmaceutical-technology.com

Immedica to buy Marinus Pharmaceuticals for $151m

As part of the deal, Immedica will add Marinus’ ZTALMY oral suspension, CV for use in patients aged two years and above. Credit: u photostock/Shutterstock. Global rare disease company Immedica Pharma has agreed to acquire Marinus Pharmaceuticals for an enterprise value of approximately $151m. Marinus is a commercial-stage pharmaceutical company engaged in the development of new therapeutics for seizure disorders. The agreement will enhance Immedica’s presence in the global rare disease market. The acquisition process, to be executed through a wholly-owned direct subsidiary of Immedica, will begin with a cash tender offer by Immedica to purchase all issued and outstanding shares of Marinus at $0.55 per share. As part of the merger deal, Immedica will add Marinus’ZTALMY (ganaxolone) oral suspension, CV. The acquisition is anticipated to speed up Immedica’s revenue growth, adding a commercial-stage asset in the US, with the potential for additional expansion worldwide. A neuroactive steroid gamma-aminobutyric acid (GABA)-A receptor positive modulator, ZTALMY received approval from the US Food and Drug Administration (FDA) in March 2022. It is indicated for treating seizures linked with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients aged two years and above. Immedica CEO Anders Edvell said: “The acquisition of Marinus represents a transformative step in Immedica’s journey to further strengthen our position as a leading rare disease company. “By adding ZTALMY to our portfolio, we significantly strengthen our capabilities and expand our presence in the US, marking a new chapter in our mission to deliver impactful therapies for underserved patient populations.” Furthermore, the deal is poised to expedite Immedica’s growth into the North American market, offering an immediate revenue-generating product and a commercial team. The board of directors of Marinus have unanimously approved the merger and recommended that stockholders tender their shares in the offer. Subject to customary conditions and approvals, the transaction is anticipated to be conclude in the first quarter of 2025. Headquartered in Stockholm, Sweden, Immedica is backed by the investment companies KKR and Impilo. The company is focused on the commercialisation of medicines for rare diseases and specialty care products. Immedica employs about 130 people across Europe, the Middle East and the US.

Drug ApprovalAcquisition

30 Dec 2024

·pipelinereview.com

Immedica to Acquire Biopharmaceutical Company Marinus Pharmaceuticals, Inc.

STOCKHOLM, Sweden & RADNOR, PA, USA I December 30, 2024 I Immedica Pharma AB (Immedica), a leading global rare disease company, and Marinus Pharmaceuticals, Inc. (Nasdaq: MRNS), a pharmaceutical company committed to improving the lives of patients with seizure disorders, today announced that they have entered into an agreement and plan of merger under which Immedica has agreed to acquire Marinus, by means of a tender offer and subsequent merger. The acquisition complements and further strengthens Immedica’s global rare disease business by adding ZTALMY® (ganaxalone) oral suspension, CV, a neuroactive steroid gamma-aminobutyric acid (GABA)-A receptor positive modulator, approved by the U.S. Food and Drug Administration (FDA) in March 2022 for the treatment of seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients two years of age and older. Transaction rationale and details in brief: “The acquisition of Marinus represents a transformative step in Immedica’s journey to further strengthen our position as a leading rare disease company. By adding ZTALMY to our portfolio, we significantly strengthen our capabilities and expand our presence in the United States, marking a new chapter in our mission to deliver impactful therapies for underserved patient populations,” said Anders Edvell, M.D. Ph.D. and Chief Executive Officer of Immedica. “Immedica is dedicated to addressing significant unmet medical needs in rare diseases, ensuring patients receive the innovative treatments they deserve. Within CDD, patients with refractory seizures face particularly challenging circumstances due to insufficiently effective existing therapies. The addition of ZTALMY allows us to offer a differentiated solution, with the potential to improve care and outcomes for these patients,” he concluded. “I am proud of the dedication and passion of our team at Marinus, which allowed us to deliver the first and only FDA-approved treatment for seizures associated with CDKL5 deficiency disorder in patients two years of age and older,” said Scott Braunstein, M.D., Chairman and Chief Executive Officer of Marinus. “With a shared commitment to improving the lives of rare disease patients, this acquisition is expected to enable ZTALMY to make an even greater impact on patients, while providing meaningful value for Marinus’ stockholders.” Transaction details Under the terms of the merger agreement, Immedica, through a wholly owned, direct subsidiary, will initiate a tender offer to acquire all the outstanding shares of Marinus common stock for a cash purchase price of USD 0.55 per share, representing a premium of 48% based on Marinus’ closing share price as of December 27 th and a premium of 97%, based on the 30-day volume-weighted average price of USD 0.28 per share preceding the announcement of the transaction. The Board of Directors of Marinus has unanimously approved the transaction and recommended that the stockholders of Marinus tender their shares in the tender offer. Immedica has received an undertaking from each director and named executive officer of Marinus to tender their respective shares in favor of the transaction. The transaction represents the culmination of Marinus’ review of strategic alternatives, which it announced on October 24, 2024, with the goal of maximizing value for its stockholders. The closing of the tender offer will be subject to customary conditions, including the tender of shares which represent at least a majority of the total number of Marinus’ outstanding shares of common stock. Upon the successful completion of the tender offer, Immedica would acquire any shares of Marinus’ common stock not tendered through a second-step merger effected for the same per share consideration. The transaction is expected to close in Q1 2025. Advisors MTS Health Partners LP is acting as Immedica’s exclusive financial advisor in connection with the transaction. Gibson, Dunn & Crutcher LLP is acting as legal counsel to Immedica and Fuchs Patentanwälte Partnerschaft mbB is acting as intellectual property counsel on this transaction, Barclays Capital Inc. is acting as Marinus´ exclusive financial advisor in connection with the transaction. Hogan Lovells LLP is acting as legal counsel to Marinus on this transaction. About ZTALMY ® (ganaxolone) oral suspension ZTALMY (ganaxolone) is a neuroactive steroid GABA A receptor modulator that acts on a well-characterized target in the brain known to have anti-seizure effects. It is a prescription medicine that has been approved by the U.S. FDA, EC, the MHRA, and the China NMPA for appropriate patients with CDKL5 deficiency disorder. U.S. Prescribing Information for ZTALMY ® (ganaxolone) oral suspension CV. European Union Summary of Product Characteristics for ZTALMY. About Marinus Pharmaceuticals Marinus is a commercial-stage pharmaceutical company dedicated to the development of innovative therapeutics for seizure disorders. The Company’s product, ZTALMY ® (ganaxolone) oral suspension CV, is an FDA-approved prescription medication introduced in the U.S. in 2022. For more information, please visit www.marinuspharma.com and follow us on Facebook , LinkedIn and X . About Immedica Immedica is a pharmaceutical company, headquartered in Stockholm, Sweden, focused on the commercialization of medicines for rare diseases and specialty care products. Immedica’s capabilities cover marketing and sales, compliance, pharmacovigilance, quality assurance, regulatory, medical affairs and market access, as well as a global distribution network serving patients in more than 50 countries. Immedica is fully dedicated to helping those living with diseases which have a large unmet medical need. Immedica’s therapeutic areas are within genetic & metabolic diseases, hematology & oncology and specialty care. Immedica was founded in 2018 and employs today around 130 people across Europe, the Middle East and the United States. Immedica is backed by the investment firms KKR and Impilo. For more information visit www.immedica.com SOURCE: Immedica

Drug ApprovalAcquisition

100 Deals associated with Ganaxolone

External Link

KEGG	Wiki	ATC	Drug Bank
D04300	Ganaxolone	-	DB05087

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Seizures	EU	Marinus Pharmaceuticals, Inc.	26 Jul 2023
Seizures	NO	Marinus Pharmaceuticals, Inc.	26 Jul 2023
Seizures	LI	Marinus Pharmaceuticals, Inc.	26 Jul 2023
Seizures	IS	Marinus Pharmaceuticals, Inc.	26 Jul 2023
CDKL5 Deficiency Disorder	US	Marinus Pharmaceuticals, Inc.	18 Mar 2022

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Drug Resistant Epilepsy	Phase 3	RU	Marinus Pharmaceuticals, Inc.	01 Oct 2013
Drug Resistant Epilepsy	Phase 3	PL	Marinus Pharmaceuticals, Inc.	01 Oct 2013
Drug Resistant Epilepsy	Phase 3	AU	Marinus Pharmaceuticals, Inc.	01 Oct 2013
Drug Resistant Epilepsy	Phase 3	BG	Marinus Pharmaceuticals, Inc.	01 Oct 2013
Drug Resistant Epilepsy	Phase 1	AU	Marinus Pharmaceuticals, Inc.	01 Oct 2013
Drug Resistant Epilepsy	Phase 1	DE	Marinus Pharmaceuticals, Inc.	01 Oct 2013
Drug Resistant Epilepsy	Phase 1	PL	Marinus Pharmaceuticals, Inc.	01 Oct 2013
Drug Resistant Epilepsy	Phase 1	RU	Marinus Pharmaceuticals, Inc.	01 Oct 2013
Drug Resistant Epilepsy	Phase 1	BG	Marinus Pharmaceuticals, Inc.	01 Oct 2013
Drug Resistant Epilepsy	Preclinical	DE	Marinus Pharmaceuticals, Inc.	01 Oct 2013

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04391569 (RAISE, Biospace) Manual	Phase 3	Epilepsy	96	Ganaxolone	dltnhjplaq(dfejchbbuf) = zjgvdcskho xqjhqhlfxe (kemfazzagx ) Met View more	Positive	17 Jun 2024
				Placebo	dltnhjplaq(dfejchbbuf) = lfmvwilyvd xqjhqhlfxe (kemfazzagx ) Met View more
CNS2023	Not Applicable	CDKL5 Deficiency Disorder	101	Ganaxolone	(tqqbayomia) = There was one death reported, which was deemed unrelated to study treatment ffqeoiblvp (rkrlnrdjfd ) View more	Positive	01 Oct 2023
IEC2023	Not Applicable	CDKL5 Deficiency Disorder	101	Ganaxolone	utvynrrzal(hpaadccvsg) = 1 tweexqssmi (ijzajihpwy ) View more	Positive	04 Sep 2023
				Placebo
IEC2023	Phase 1	-	36	IV ganaxolone 10mg	agszpxxvwt(skoqcthvmy) = No deaths were reported znscltrpio (kectrybcvx ) View more	-	04 Sep 2023
				IV ganaxolone 30mg
NCT00442104 (CTgov)	Phase 2	Spasms, Infantile	54	Ganaxolone	tnstzjkncr(zqzotdugyy) = mzzlirtcyr kjbhaculsx (mhiixkklmp, wihllwaded - batzkpfmkt) View more	-	02 Jun 2023
NCT01725152 (CTgov)	Phase 2	Fragile X Syndrome	59	Ganaxolone (Ganaxolone)	ecvhouzhov(fvnwxkbkds) = uylaqwotgl egtshgizrh (tdgiiylrrg, ssimvwhumt - bcahqbsutn) View more	-	10 Apr 2023
				placebo+Ganaxolone (Placebo)	ecvhouzhov(fvnwxkbkds) = ecpnjpetsg egtshgizrh (tdgiiylrrg, dbtdotphot - jpeswhvlol) View more
NCT04285346 (TSC, CTgov)	Phase 2	Tuberous Sclerosis	23	Ganaxolone (Treatment Period: Ganaxolone)	vphxyutdqt(avkqhkhgjt) = kwpidmlppi rntuqbwbfs (bfzrtnvfcj, abexbcfzed - jqjlultxwz) View more	-	04 Apr 2023
				Ganaxolone (Open Label: Ganaxolone)	hrwhcozgpd(mmhtzixcfm) = rsktuovhga bguzcptmsz (nsbvbnlgos, ishxcodufq - pdwrwwtpls) View more
NCT00465517 (CTgov)	Phase 2	Seizures \| Epilepsies, Partial	147	Ganaxolone	mchgcxgmim(civybavivy) = rrkvcgmxmd fimknbwjju (bjobvfxhou, hrivbmwigo - efbkikotzi) View more	-	15 Mar 2023
NCT02519439 (CTgov)	Phase 3	Drug Resistant Epilepsy	26	ganaxolone	tntnzxknqw(lskpsoyobx) = spzgljlyen pyfpamzmny (bwjobuixzs, jndxiofsho - glnoucjyzc) View more	-	14 Feb 2023
NCT01963208 (CTgov)	Phase 3	Drug Resistant Epilepsy	405	Ganaxolone (Double Blind: Cohort 2 - Ganaxolone)	srmgpmxqmd(txsxecyoeg) = qbwsfnrlnc osdjqpcbsw (plyoudxkcx, bduwkdeeev - yuorgbrfyw) View more	-	14 Feb 2023
				Placebo+AED+ganaxolone (Double Blind: Cohort 2 - Placebo)	srmgpmxqmd(txsxecyoeg) = vwdrlbclok osdjqpcbsw (plyoudxkcx, xzwdtzbaet - khgejvhgob) View more

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