Marinus Pharmaceuticals, Inc. (Nasdaq: MRNS), a pharmaceutical company dedicated to the development of innovative therapeutics to treat seizure disorders, today announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the use of its lead product candidate ganaxolone, to treat seizures associated with CDKL5 deficiency disorder (CDD), a rare, genetic epilepsy. An NDA filing notification letter from the FDA is expected before the end of Q3 2021. If the NDA is accepted for filing by the FDA, this will enable the company to draw $30 million of additional cash under its credit financing agreement with Oaktree Capital Management, L.P., on or before December 31, 2021, subject to the satisfaction of certain customary conditions described in the credit agreement.

“We have been diligently focused on advancing ganaxolone’s clinical development for patients suffering from CDD, a devastating disease with high unmet medical need, and are pleased to have reached this important milestone,” said Joseph Hulihan, M.D., Chief Medical Officer of Marinus. “We look forward to working with the FDA in their review process and remain focused on preparing for the anticipated U.S. launch. With our European commercial partner in place, we are equally committed to advancing ganaxolone for CDD patients in markets outside the U.S. and plan to submit a marketing authorization application to the European Medicines Agency later this year.”

The NDA is supported by data from the Phase 3 Marigold trial, a double-blind placebo-controlled trial in which 101 patients treated with ganaxolone showed a 30.7% median reduction in 28-day major motor seizure frequency, compared to a 6.9% reduction for those receiving placebo, achieving the trial’s primary endpoint (p=0.0036). Patients in the Marigold open label extension study treated with ganaxolone for at least 12 months (n=48) experienced a median 49.6% reduction in major motor seizure frequency. Ganaxolone was generally well-tolerated with a safety profile consistent with previous clinical trials, with the most frequent adverse event being somnolence.

The NDA includes a request for Priority Review, which, if granted, accelerates the timing of the FDA’s goal for review of the application to six months following the end of the 60-day filing review period rather than the standard 10 month review. Priority Review status is designated for drugs that may offer a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious condition.

The NDA also includes a request for a Rare Pediatric Disease Priority Review Voucher (PRV). The PRV program is designed to encourage development of new drugs and biologics for the prevention or treatment of rare pediatric diseases. Marinus received Rare Pediatric Disease (RPD) Designation from the FDA for ganaxolone for the treatment of seizures associated with CDD in July 2020. If the ganaxolone application is approved and the PRV is granted, Marinus may use it to obtain priority review for a subsequent human drug or biologic application or can sell or transfer the PRV to a third party.

Pipeline and Corporate Update

Due to COVID-19 priorities in several academic medical centers participating in the Phase 3 RAndomized Therapy In Status Epilepticus (RAISE) trial, including staff turnover and the need for clinical sites to devote significant resources to patients with COVID-19, the trial has experienced site initiation and enrollment delays. Given these most recent challenges, which heightened in the second quarter of this year, Marinus is shifting its top-line data readout for the RAISE trial to 2H 2022. The company now expects the vast majority of sites to be open by end of Q3 2021.

Marinus recently announced an agreement with Finland-based pharmaceutical company, Orion Corporation, in which Orion received exclusive rights to commercialize the oral and intravenous (IV) dose formulations of ganaxolone in Europe for CDKL5 deficiency disorder, tuberous sclerosis complex and refractory status epilepticus. Under the agreement, Orion will pay Marinus €25 million (~$30 million) in cash as an upfront fee. Marinus is eligible to receive up to an additional €97 million (~$115 million) in R&D reimbursement and cash milestone payments based on specific clinical and commercial achievements, as well as tiered royalty payments based on net sales that could reach the high teens for the oral programs and low 20s for the IV program. Further details are available in Marinus’ press release distributed August 3, 2021 (Marinus Pharmaceuticals Announces Exclusive Collaboration with Orion Corporation for European Commercialization of Ganaxolone).

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.

About Ganaxolone

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 1,800 pediatric and adult subjects across various indications at therapeutically relevant dose levels and treatment regimens for up to more than two years.

About Marinus Pharmaceuticals

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 and is conducting a Phase 2 trial in tuberous sclerosis complex and a Phase 3 trial in refractory status epilepticus.