Rare Daily Staff

The Committee for Medicinal Products for Human Use of the European Medicines Agency granted accelerated assessment to its lead product candidate, ganaxolone, for the treatment of seizures associated with CDKL5 deficiency disorder, a rare, genetic epilepsy.

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. Currently, there are no therapies approved specifically for CDD.

Ganaxolone, a positive allosteric modulator of GABAA receptors, is an experimental 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 in treatment regimens for up to more than two years.

“We believe this accelerated assessment by the EMA underscores ganaxolone’s potential to address areas of unmet medical need for patients and families afflicted by CDD,” said Kimberly McCormick, senior vice president and head of regulatory affairs at Marinus. “We plan to submit a marketing authorization application by the end of the third quarter and look forward to working with the EMA during its review of the application. If approved, our collaboration with Orion Corporation supports our efforts to bring ganaxolone to European markets as quickly as possible for CDD patients who may benefit.”

Accelerated assessment is granted by the CHMP when a medicinal product is expected to be of major public health interest and therapeutic innovation. Accelerated assessment potentially provides a reduced review timeline from 210 to 150 days once the marketing authorization application (MAA) is filed and validated, not counting clock stops when applicants are requested to provide additional information.

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

The endorsement by the CHMP follows Marinus’ recent submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration for the use of ganaxolone to treat seizures associated with CDD. An NDA filing notification letter from the FDA is expected before the end of the third quarter of 2021.

Photo: Kimberly McCormick, senior vice president and head of regulatory affairs at Marinus

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