Shares of Marinus Pharmaceuticals Inc. (NASDAQ:MRNS) climbed 51.7% to close at $3.20 on Sept. 15 following news that the company's sole clinical asset, ganaxolone, met the primary endpoint of its phase III Marigold study in CDKL5 deficiency disorder (CDD), a rare genetic condition that can leave children unable to walk, talk or feed themselves. Management expects to file an NDA for the drug around mid-2021, followed by an MAA by the end of the third quarter of 2021. If the NDA is approved, Marinus would have the first drug approved for the treatment of CDD and may be eligible to receive a priority review voucher from the FDA, it said.

CDKL5 deficiency disorder is caused by a mutation of the CDKL5 gene, located on the X chromosome. It's a gene that encodes proteins essential for normal brain function. The early-onset condition, which affects mostly girls, is characterized by difficult-to-control seizures.

The double-blind, placebo-controlled trial enrolled 102 children and young adults, ages 2 to 21, adding a thrice-daily dose of ganaxolone to their existing anti-seizure treatment or a placebo. Those treated with ganaxolone during the study showed a 32.2% median reduction in 28-day major motor seizure frequency vs. a 4% reduction for placebo.

Kids enrolled in the study had a median of a little less than 60 seizures per month, making the reduction of frequency "a great outcome for patients" that delivered "a material impact for the quality of life for these kids and for their caregivers," Marinus CEO Scott Braunstein said Tuesday.

The trial also hit at least one of its secondary endpoints, he said: a reduction in seizure intensity, something that could have a meaningful impact on activities of daily living. Though the trial "showed numerical trends favoring ganaxolone" across several other predefined secondary endpoints, those measures did not meet statistical significance, the company said.

Ganaxolone, a GABA A receptor agonist, was generally well-tolerated in the study, with a safety profile consistent with previous trials. The most frequent adverse event was somnolence.

In addition to CDD, Marinus is also advancing ganaxolone in the Violet study, an ongoing placebo-controlled phase II trial in PCDH-19-related epilepsy and is working with the FDA to get a planned phase III trial of I.V. ganaxolone in refractory status epilepticus (RSE) off the ground. Data from the Violet study are expected in the first half of 2021, while the company is targeting the first half of 2022 for top-line data from the RSE trial.

Marinus plans on reporting data from a phase II trial of ganaxolone in tuberous sclerosis complex in mid-2021 and, should that readout support it, could begin a phase III registrational trial in that indication shortly thereafter.

Outside a busy slate of civilian applications, Marinus said it’s also working on a more tailored program for the U.S. Biomedical Advanced Research and Development Authority (BARDA), which has agreed to fund $51 million of an $84 million contract for the company to support clinical development of I.V. ganaxolone for individuals exposed to nerve gas, such as sarin.

The BARDA agreement includes $21 million in nondilutive funding to support the phase III trial Marinus is planning in RSE and preclinical studies of ganaxolone in nerve agent exposure animal models, with up to $30 million in additional optional funding contingent on favorable clinical and preclinical outcomes, it said. Marinus would be responsible for chipping in up to up to $33 million in cost-sharing contributions if all development options are completed.