RARE Daily

European Commission Approves Marinus’s Ztalmy for Epileptic Seizures Associated with CDKL5 Deficiency Disorder

July 31, 2023

Rare Daily Staff

The European Commission granted approval of Marinus Pharmaceuticals’ Ztalmy oral suspension for the adjunctive treatment of epileptic seizures associated with neurodevelopmental condition CDKL5 deficiency disorder in patients 2 to 17 years of age.

Ztalmy may be continued in patients 18 years of age and older.

CDKL5 deficiency disorder (CDD) is a serious and rare genetic disorder characterized by early‑onset, difficult‑to‑control seizures and severe neuro‑developmental impairment. It is caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome. The CDKL5 gene produces a protein that is important for normal brain development and function. Ztalmy is a neuroactive steroid GABAA receptor modulator that acts on a well-characterized target in the brain known to have anti-seizure effects.

The EC approval of Ztalmy in CDD is supported by data from the phase 3 Marigold double-blind placebo-controlled trial, in which 101 patients were randomized and individuals treated with Ztalmy showed a median 30.7 percent reduction in 28-day major motor seizure frequency, compared to a median 6.9 percent reduction for those receiving placebo, achieving the trial’s primary endpoint. In the Marigold open label extension study, patients treated with Ztalmy for at least 12 months experienced a median 49.6 percent reduction in major motor seizure frequency.

In the clinical development program, Ztalmy demonstrated efficacy, safety and tolerability with the most common adverse reactions (incidence ≥5 percent and at least twice the rate of placebo) in the Ztalmy group being somnolence, pyrexia, salivary hypersecretion and seasonal allergy. In May 2022, the results from the Marigold study were published in The Lancet Neurology.

The approval follows a positive opinion issued in May 2023 by the Committee for Medicinal Products for Human Use of the European Medicines Agency and is applicable to all 27 European Union member states plus Iceland, Norway and Liechtenstein. In July 2021, Marinus and Orion Corporation entered into a collaboration agreement which grants Orion the right to commercialize Ztalmy in Europe.

“The approval by the European Commission represents a significant milestone for children, families and physicians who, until now, have long been challenged by the impact of seizures and lack of treatments available for CDD,” said Scott Braunstein, chairman and CEO of Marinus.

Photo: Scott Braunstein, chairman and CEO of Marinus

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