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 it has received a positive response from the U.S. Food and Drug Administration (FDA) that the efficacy and safety data resulting from the company’s pivotal Phase 3 Marigold Study on the use of oral ganaxolone in children and young adults with CDKL5 deficiency disorder (CDD) appear sufficient to support the filing of a New Drug Application (NDA). Adequacy of these data to support an approval of ganaxolone for the proposed indication will be a matter of future FDA review.
CDD is a rare, genetic epilepsy with refractory seizures. Marinus provided the data to the FDA in a briefing document meant to support a Type C meeting, and the FDA provided written preliminary comments in response. Based on this feedback, Marinus is targeting a pre-NDA meeting by the end of Q1 to support submission.
“We are pleased with the FDA’s assessment of the sufficiency of the efficacy and safety data from one Phase 3 clinical trial to support an NDA filing,” said Scott Braunstein, M.D., Chief Executive Officer of Marinus. “We remain on track to submit the NDA for use of ganaxolone in CDD for FDA review by mid-2021 and look forward to continued advancement of ganaxolone as the first potential FDA approved treatment specifically indicated in patients diagnosed with CDD.”
In September, Marinus reported positive topline data from the Phase 3 Marigold Study, the first double-blind placebo-controlled trial to provide evidence of efficacy in CDD and the first Phase 3 trial to examine three times a day dosing of ganaxolone in pediatric patients.
In the Phase 3 Marigold trial, patients treated with ganaxolone showed a significant 32.2% median reduction in 28-day major motor seizure frequency, compared to a 4.0% reduction for those receiving the placebo, achieving the trial’s primary endpoint (p=0.002). In this trial, ganaxolone was generally well tolerated with a safety profile consistent with previous clinical trials, with the most frequent adverse event being somnolence.
“We see continued progress in our other development programs,” continued Dr. Braunstein. “Marinus continues to initiate new sites to participate in the Phase 3 clinical trial of IV ganaxolone for the treatment of Refractory Status Epilepticus (RSE) or RAISE trial. While the COVID-19 pandemic is lengthening the time for new trial sites to open for enrollment, we do not anticipate this having major implications on the ultimate timing of trial results.”
“The Phase 2 Violet Study, evaluating both three times a day dosing of ganaxolone and the role of allopregnanolone sulfate as a biomarker in PCDH19-related epilepsy remains on track. In March, we plan to provide an update on this program,” said Dr. Braunstein. “Additionally, we expect to report top line data from our Phase 2 Tuberous Sclerosis Complex trial by late Q2.”
About CDKL5 Deficiency Disorder
CDKL5 deficiency disorder (CDD) is a serious and rare genetic disorder that is caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome. CDD is characterized by early-onset, difficult-to-control seizures and severe neuro-developmental impairment. Most children affected by CDD cannot walk, talk, or feed themselves. Currently, there are no therapies approved specifically for CDD.
Ganaxolone, a positive allosteric modulator of GABAA receptors, is 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. Unlike benzodiazepines, ganaxolone exhibits antiseizure, antidepressant and anti-anxiety activity via its effects on synaptic and extrasynaptic GABAA receptors. More than 1,600 study participants, both adults and children, have received ganaxolone at therapeutically relevant dose levels and treatment regimens for up to four years.
About Marinus Pharmaceuticals
Marinus Pharmaceuticals, Inc. is a pharmaceutical company dedicated to the development of innovative therapeutics to treat rare 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 recently completed the first ever Phase 3 pivotal trial in children with CDKL5 deficiency disorder and is conducting a Phase 2 trial in tuberous sclerosis complex, as well as a Phase 2 biomarker-driven proof-of-concept trial in PCDH19-related epilepsy. The company is initiating a Phase 3 trial in status epilepticus.
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 clinical development plans for ganaxolone; our plans to have a pre-NDA meeting with FDA for submission of an NDA for use of ganaxolone in CDKL5 Deficiency Disorder (CDD) by the end of first quarter 2021; our expectations to file an NDA for ganaxolone in CDD by end of second quarter 2021; our ability to receive FDA approval of ganaxolone in CDD; our plan to provide an update on our Phase 2 Violet Study in March 2021; our expectations that COVID-19 will not have major implications on the ultimate timing of trial results for our RAISE Phase 3 clinical trial in Refractory Status Epilepticus; our expectation to report top line data from our Phase 2 Tuberous Sclerosis Complex trial by late second quarter 2021. 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, uncertainties and delays relating to the design, enrollment, completion, and results of clinical trials; unanticipated costs and expenses; clinical trial results may not support further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the interpretation of clinical trial results and the ability of clinical trial results to support regulatory approval; our ability to obtain and maintain regulatory approval for our product candidate; delays, interruptions or failures in the manufacture and supply of our product candidate; our ability to raise additional capital; the effect of the COVID-19 pandemic on our business, the medical community 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. 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.