03 December 2021
RADNOR, Pa.--(BUSINESS WIRE)-- Marinus Pharmaceuticals, Inc. (Nasdaq: MRNS), a pharmaceutical company dedicated to the development of innovative therapeutics to treat rare seizure disorders, today announced new clinical trial and research data being presented at the American Epilepsy Society (AES) Annual Meeting in Chicago, Illinois, including new quality of life and extended safety and efficacy data of ganaxolone in CDKL5 deficiency disorder (CDD) and a quantitative EEG analysis and case reports of patients in super-refractory status epilepticus.
“We are honored to be at the AES Meeting this year after almost a year of planning from our medical and scientific affairs, clinical, and advocacy teams, with nine presentations spanning our IV and oral portfolio—Marinus’ largest data showing to date,” said Scott Braunstein, M.D., Chief Executive Officer of Marinus Pharmaceuticals. “We look forward to sharing clinical trial data supporting the potential of ganaxolone to treat a range of seizure disorders as well as research data highlighting the impact that seizures can have on developmental progressions and quality of life in children with CDD.”
Marinus’ poster presentations are summarized below:
Utilization of Quantitative EEG Spectral Analysis to Characterize IV Ganaxolone PK/PD Properties in Refractory Status Epilepticus (RSE)
An analysis from continuous EEG recordings in 17 patients enrolled in the Phase 2 refractory status epilepticus (RSE) study demonstrated a substantial increase in the alpha/delta ratio immediately after the start of IV ganaxolone in 75% of patients. The median time-to-peak and corresponding median percentage increase in the alpha/delta ratio were five minutes and 93% respectively, matching the observed median time to status epilepticus cessation. For the suppression ratio, an increase was observed in 50% of patients, with a median time-to-peak of six minutes and median percentage increase of 53%. Relative changes in alpha/delta ratio and suppression ratio correlated with measured serum ganaxolone levels. This post-hoc analysis of IV ganaxolone in RSE showed changes in quantitative EEG measures and is a reasonable continuous biomarker to assess physiological activity of IV ganaxolone in humans.
IV Ganaxolone in Pediatric Super-Refractory Status Epilepticus: Two Case Presentations
Two pediatric patients with super-refractory status epilepticus (SRSE) were treated under emergency investigational new drug applications with IV ganaxolone.Results showed ganaxolone was effective in terminating SRSE in both pediatric patients, permitting IV anesthetics to be weaned and seizure control was maintained after transitioning to adjunctive oral ganaxolone.
Extended Duration Safety and Efficacy of Adjunctive Ganaxolone Treatment in Patients with CDKL5 Deficiency Disorder: 8-Month Minimum Open-Label Extension Follow-up
Data from the open-label extension (OLE) phase of the Phase 3 Marigold Study in CDKL5 deficiency disorder (CDD) provide supportive evidence for maintenance of effect on reducing major motor seizures associated with CDD at approximately eight months and up to 12 months in patients who continue ganaxolone treatment. The median major motor seizure frequency reduction from baseline in the OLE was 30.1% in patients continuing ganaxolone (n=38) and 33.3% in patients transitioning from placebo (n=34) at eight months and 46.5% (n=22) and 53.8% (n=26), respectively, at 12 months. Safety findings from this OLE analysis are consistent with the safety in the double-blind phase as well as the known safety profile of gananxolone. These preliminary findings indicate that ganaxolone may have the potential to provide sustained seizure improvements in patients with CDD.
Longitudinal Relationship Between Seizure Burden and Developmental Progression and the Implications on Quality of Life in Children with CDKL5 Deficiency Disorder
This study included longitudinal data from the International CDKL5 Disorder Database on 143 children whose caregivers completed a baseline and follow-up questionnaire. The findings suggest that reduced seizure burden in patients with CDD may lead to improved developmental outcomes when adjusting for key factors. Additionally, improved developmental outcomes may lead to improved patient quality of life. These data suggest that the clinical progression for an individual child is not necessarily predetermined and may be able to be positively influenced by optimal seizure management and developmental support.
Effect of Ganaxolone on Quality of Life in Children with CDKL5 Deficiency Disorder
Quality of life (QOL) is a critical outcome for evaluating the success of interventions. Along with a reduction in frequency of major motor seizures, children in the Phase 3 CDD Marigold Study who received ganaxolone had higher QOL scores than children in the placebo group when controlling for potential confounding factors, although the estimates lacked precision. Future analysis of the Marigold data will investigate the reasons for improved QOL following administration of ganaxolone.
Ganaxolone Treatment in Patients with CDKL5 Deficiency Disorder with Comorbid Lennox-Gastaut Syndrome: A Post-hoc Analysis from the Marigold Study
In this post-hoc analysis, ganaxolone treatment was associated with decreases in major motor seizure frequency in four of six patients with CDD and Lennox-Gastaut syndrome (LGS). Of 101 patients randomized in the Phase 3 CDD Marigold Study, seven had a co-diagnosis of LGS. Of the seven patients, two were initially randomized to ganaxolone and five to placebo. One patient in the placebo arm did not enter the open label extension (OLE) phase, therefore six patients were evaluable for this analysis. Compared to baseline, the two ganaxolone patients in the double-blind phase experienced a reduction in major motor seizure frequency (MMSF) of 25.4% and 43.5% at the end of the 17 weeks of ganaxolone treatment. Two of the four patients who were initially randomized to placebo and transitioned to open label ganaxolone demonstrated improvements in seizure frequency at 17 weeks of ganaxolone treatment (-21.0% and -36.3% change in MMSF). The remaining two patients in the OLE did not show improvement while on ganaxolone (4.6% and 27.1% change in MMSF). Ganaxolone was generally well-tolerated and no new safety findings emerged in the LGS subgroup. Larger studies may further elucidate the potential of ganaxolone as a treatment for seizures associated with LGS.
Phase 2 Open-Label Clinical Study Evaluating Oral Ganaxolone for the Treatment of Seizures Associated with Tuberous Sclerosis Complex
Ganaxolone was studied in a highly refractory tuberous sclerosis complex (TSC) patient population in which 83% of the patients were on concomitant newer generation antiseizure medications including cannabidiol, everolimus or both. Participants treated with ganaxolone experienced a modest median percent reduction in seizure frequency with approximately one third of patients experiencing a greater than 50% seizure reduction. Ganaxolone was generally well-tolerated with somnolence reported as the most common adverse event, consistent with previous trials. Based on the results of this proof-of-concept trial, a Phase 3 study of ganaxolone in refractory TSC-associated seizures is planned.
Phase 2, Placebo-Controlled Clinical Study of Oral Ganaxolone in PCDH19-Clustering Epilepsy (the Violet Study)
Despite the limited sample size (N=21), patients treated with ganaxolone experienced directional improvements in seizure frequency compared to those on placebo. Ganaxolone was generally well tolerated with no new safety findings. Due to seizure cluster fluctuation in PCDH19-clustering epilepsy, novel epilepsy clinical trial designs may be needed for future studies.
Aggregated Safety and Tolerability Experience from the Ganaxolone Development Program
Ganaxolone has been dosed in 46 studies and over 1,900 subjects. In placebo-controlled studies, there were 1,844 patients who received either placebo (743) or ganaxolone (1101). The frequency of treatment-emergent adverse events (TEAE) was 62.9% for ganaxolone and 53.8% for placebo. The serious adverse event (SAE) rate was similar between ganaxolone and placebo-treated patients at 2.8% and 3.8%, respectively. The most frequently reported TEAEs (>5% of subjects) in ganaxolone-treated subjects were somnolence, dizziness, fatigue and headache. The experience with the investigational use of ganaxolone in studies conducted to date suggests an acceptable tolerability and safety profile.
Marinus investor event:
Marinus Pharmaceutical Virtual Investor Event at American Epilepsy Society 2021 Annual Meeting
Date and Time: Monday, Dec. 6th, 1:00-2:30 p.m. ET (12:00-1:30 p.m. CT)
Ganaxolone, a positive allosteric modulator of GABAA receptors, is an investigational product being developed in intravenous and oral formulations intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Ganaxolone exhibits anti-seizure and anti-anxiety activity via its effects on synaptic and extrasynaptic GABAA receptors. Ganaxolone has been studied in more than 1,900 pediatric and adult subjects across various indications at therapeutically relevant dose levels and treatment regimens for up to more than two years.
Marinus Pharmaceuticals, Inc. is a pharmaceutical company dedicated to the development of innovative therapeutics to treat seizure disorders. Ganaxolone is a positive allosteric modulator of GABAA receptors that acts on a well-characterized target in the brain known to have anti-seizure, antidepressant and anti-anxiety effects. Ganaxolone is being developed in IV and oral dose formulations intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Marinus completed the first ever Phase 3 pivotal trial in children with CDKL5 deficiency disorder last year, is planning to conduct a Phase 3 trial in tuberous sclerosis complex, and a Phase 3 trial in refractory status epilepticus is ongoing. For more information visit www.marinuspharma.com.
To the extent that statements contained in this press release are not descriptions of historical facts regarding Marinus, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as "may", "will", "expect", "anticipate", "estimate", "intend", "believe", and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Examples of forward-looking statements contained in this press release include, among others, statements regarding our expected clinical development plans, and the potential safety and efficacy of ganaxolone, as well as its therapeutic potential in a number of indications.
Forward-looking statements in this press release involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the risk that the FDA will require additional clinical trials or data; any delays in review of the NDA submission by the FDA for any reason, including the COVID-19 pandemic; the timing of regulatory filings for our product candidates; the potential that regulatory authorities, including the FDA and EMA, may not grant or may delay approval for our product candidate; uncertainties and delays relating to the design, enrollment, completion, and results of clinical trials; unanticipated costs and expenses; early clinical trials may not be indicative of the results in later clinical trials; clinical trial results may not support regulatory approval or further development in a specified indication or at all; actions or advice of the FDA or EMA may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; our ability to obtain and maintain regulatory approval for our product candidate; our ability to obtain, maintain, protect and defend intellectual property for our product candidates; the potential negative impact of third party patents on our or our collaborators’ ability to commercialize ganaxolone; delays, interruptions or failures in the manufacture and supply of our product candidate; the size and growth potential of the markets for the company’s product candidates, and the company’s ability to service those markets; the company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the company’s expectations, projections and estimates regarding expenses, future revenue, capital requirements, and the availability of and the need for additional financing; the company’s ability to obtain additional funding to support its clinical development programs; the company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the company’s product candidates; the potential for Orion to breach the collaboration or terminate the agreement in accordance with its terms; the potential for Orion to recoup a percentage of the upfront fee depending on the additional pre-clinical testing; the effect of the COVID-19 pandemic on our business, the medical community, regulators and the global economy; and the availability or potential availability of alternative products or treatments for conditions targeted by us that could affect the availability or commercial potential of our product candidate. This list is not exhaustive and these and other risks are described in our periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.Print
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