Study designed to evaluate a clinically relevant predictive biomarker that aims to identify high responding patients
RADNOR, Pa., March 06, 2019 (GLOBE NEWSWIRE) -- Marinus Pharmaceuticals, Inc. (MRNS) (“Marinus” or “Company”), a biopharmaceutical company dedicated to the development of innovative therapeutics to treat epilepsy and neuropsychiatric disorders, today announced that it is initiating a single global pivotal Phase 3 clinical study (Violet Study) evaluating oral ganaxolone in children with PCDH19-related epilepsy (PCDH19-RE), a rare genetic epilepsy. If successful, the Violet Study is intended to support the regulatory filings for approval of ganaxolone in this underserved and refractory patient population.
The Violet Study is a global, double-blind, randomized, placebo-controlled pivotal Phase 3 clinical study evaluating ganaxolone in children with PCDH19-RE. The study will enroll up to 70 patients between the age of 1 and 17 with a confirmed PCDH19 mutation. All patients that meet eligibility will be stratified into one of two biomarker groups and randomized (ganaxolone or placebo) within each stratum. The trial will consist of an 8-week prospective baseline period to collect seizure data, followed by a 17-week double-blind treatment phase. Patients randomized to ganaxolone will titrate over four weeks to a dose of up to 600 mg of ganaxolone oral liquid suspension three times a day and maintain that dose for the following 13-weeks. After the double-blind period, all patients who meet certain eligibility requirements will have the opportunity to receive ganaxolone in an open label phase of the study. The Company expects to begin screening patients for enrollment into the study in the second quarter of 2019 and data from the study are estimated to be available in 2021.
“Following our End-of-Phase 2 meeting with the FDA and Scientific Advice from the EMA, we are extremely excited at the prospect of incorporating a potentially clinically useful and predictive neurosteroid biomarker into our clinical trial,” said Dr. Lorianne Masuoka, Chief Medical Officer of Marinus. “We believe this could be the beginning of a targeted, personalized treatment for patients suffering from rare genetic epilepsies. A neurosteroid biomarker that can predict response may have potential applications in epileptic conditions beyond PCDH19. This new pivotal study in PCDH19 along with our on-going Phase 3 trial in CDKL5 Deficiency Disorder (Marigold Study) strengthens Marinus’ commitment to rare forms of refractory pediatric epilepsy with no approved therapies.”
In the Company’s open-label phase 2 clinical trial in 11 patients with PCDH19-RE, patients receiving ganaxolone experienced a 25% decrease in median seizure frequency compared to baseline. At the American Epilepsy Society Annual Meeting in December 2018, the Company reported additional data which identified preliminary evidence of a plasma neurosteroid biomarker that correlated with seizure response in 10 of the 11 PCDH19-RE patients treated with ganaxolone. The post-treatment review of baseline plasma neurosteroid levels in patients with PCDH19-RE revealed a significant association between these neurosteroid levels and response to ganaxolone treatment. Patients with a very low level of a specific neurosteroid level showed a medically notable reduction in median seizure frequency of 50% (n=7) compared to an 84% increase in median seizure frequency seen in patients with a very high level of the same specific neurosteroid (n=4). The difference in the levels of the neurosteroid between responders and non-responders was approximately 1.5 orders of magnitude. This clinical finding corroborates the scientific rationale for ganaxolone to provide a benefit to patients with very low levels of an allopregnanolone associated neurosteroid.
Marinus has received orphan drug designation for PCDH19.
More information on the Violet Study will be available at https://www.marinuspharma.com/for-patients-families/pcdh19-related-epilepsy or www.clinicaltrials.gov.
About PCDH19-related Epilepsy
Protocadherin 19 -related epilepsy (PCDH19-RE) is a serious and rare epileptic disease characterized by highly variable early-onset cluster seizures with comorbid cognitive and behavioral disturbances with or without intellectual disability. About 1 in 10 girls who begin having seizures before the age of 5 has PCDH19-RE. The features of PCDH19-RE can overlap or look similar to the features in Dravet Syndrome. It is estimated that there are approximately 10,000–12,000 children worldwide with PCDH19-RE.
Currently, there are no approved therapies for PCDH19-RE. Any therapy that reduces the frequency, duration or severity of seizures may positively impact quality of life for the child and family.
Ganaxolone, a positive allosteric modulator of GABAA, is being developed in three different dose forms (intravenous, capsule and liquid) intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Unlike benzodiazepines, ganaxolone exhibits anti-seizure and anti-anxiety activity via its effects on synaptic and extrasynaptic GABAA receptors. Ganaxolone has been studied in more than 1,600 subjects, both pediatric and adult, at therapeutically relevant dose levels and treatment regimens for up to four years. In these studies, ganaxolone was generally safe and well-tolerated. The most commonly reported adverse events were somnolence, dizziness and fatigue.
About Marinus Pharmaceuticals
Marinus Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to the development of ganaxolone, which offers a new mechanism of action, demonstrated efficacy and safety, and convenient dosing to improve the lives of patients suffering from epilepsy and depression. Ganaxolone is a positive allosteric modulator of GABAA that acts on a well-characterized target in the brain known to have anti-seizure, anti-depressant and anti-anxiety effects. Ganaxolone is being developed in three different dose forms (IV, capsule and liquid) intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Marinus has initiated the first ever pivotal studies in children with CDKL5 deficiency disorder and PCDH19-related epilepsy and is currently conducting studies in women with postpartum depression and patients with refractory status epilepticus. For more information visit www.marinuspharma.com. Please follow us on Twitter: @MarinusPharma.
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”, “is planning”, 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 interpretation of preclinical studies, development plans for our product candidate, including the development of dose forms, the clinical trial testing schedule and milestones, the ability to complete enrollment in our clinical trials, interpretation of scientific basis for ganaxolone use, timing for availability and release of data, the safety, potential efficacy and therapeutic potential of our product candidate and our expectation regarding the sufficiency of our working capital. Forward-looking statements in this 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 uncertainties inherent in the conduct of future clinical trials, that results of preclinical studies or earlier clinical trials are not necessarily predictors of future results in later preclinical studies or clinical trials, the timing of the clinical trials, enrollment in clinical trials, availability of data from ongoing clinical trials, expectations for regulatory approvals, the attainment of clinical trial results that will be supportive of regulatory approvals, and other matters, including the development of formulations of ganaxolone, and the availability or potential availability of alternative products or treatments for conditions targeted by the Company that could affect the availability or commercial potential of our drug candidates. Marinus undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the Company in general, see filings Marinus has made with the Securities and Exchange Commission.
Lisa M. Caperelli
Executive Director, Investor & Strategic Relations
Marinus Pharmaceuticals, Inc.