The Food and Drug Administration (FDA) has approved Ztalmy® (ganaxolone) for the treatment of seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients 2 years of age and older.
CDD is a rare genetic disorder that results in difficult-to-control seizures and severe neurodevelopmental delay. Ztalmy is a neuroactive steroid gamma-aminobutyric acid (GABA) A receptor positive modulator designed to regulate brain activity by inhibiting the abnormal electrical discharges that cause seizures and status epilepticus.
The approval was based on data from the randomized, placebo-controlled, double-blind phase 3 Marigold study (ClinicalTrial.gov Identifier: NCT03572933) that evaluated the efficacy and safety of Ztalmy in 101 patients aged 2 to 19 years with genetically confirmed CDKL5 gene mutation. Patients were randomly assigned 1:1 to receive either Ztalmy or placebo, in addition to their existing stable regimen, for 17 weeks. In the Ztalmy arm, patients weighing 28kg or less received 21mg/kg (maximum daily dose of 1800mg) three times daily and those weighing more than 28kg received 600mg three times daily.
Findings showed that treatment with Ztalmy resulted in a 30.7% median reduction in 28-day major motor seizure frequency (primary endpoint) compared with a 6.9% reduction with placebo (P =.0036). In an open-label extension study, patients treated with Ztalmy for at least 12 months (n=48) experienced a 49.6% median reduction in major motor seizure frequency.
As for safety, the most common adverse reactions (incidence of at least 5% with Ztalmy and at least twice the rate of placebo) were somnolence, pyrexia, salivary hypersecretion, and seasonal allergy. Patients treated with antiepileptic drugs, including Ztalmy, should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, or any usual changes in mood or behavior.
“As the mother of a daughter living with CDD, I’ve experienced first-hand the devastating impact seizures can have on these patients,” said Karen Utley, President and Co-founder of the International Foundation for CDKL5 Research. “This approval is monumental for the CDD community, bringing not only the first approved treatment option specifically for CDD patients, but renewed hope to those who have struggled to find medications that are effective in significantly reducing the number of seizures these patients experience on a daily basis.”
Ztalmy is supplied as a 135mL bottle containing 50mg/mL of ganaxolone oral suspension in a carton of 1- or 5-bottles. The product is expected to be commercially available in July 2022 following scheduling by the US Drug Enforcement Administration (DEA).
The Company will also launch The Ztalmy One Program to help eligible patients gain access to treatment.
- Marinus Pharmaceuticals announces FDA approval of Ztalmy® (ganaxolone) for CDKL5 deficiency disorder. News release. Marinus Pharmaceuticals, Inc. Accessed March 18, 2022. https://www.businesswire.com/news/home/20220318005282/en/Marinus-Pharmaceuticals-Announces-FDA-Approval-of-ZTALMY%C2%AE-ganaxolone-for-CDKL5-Deficiency-Disorder
- Ztalmy. Package insert. Marinus Pharmaceuticals, Inc.; 2022. Accessed March 18, 2022. https://marinuspharma.com/wp-content/uploads/2022/03/prescribing-information.pdf