Case Study : US FDA approval of Marinus Pharma’s Ztalmy

Marinus Pharmaceuticals, Inc., a pharmaceutical company dedicated to the development of innovative therapeutics to treat seizure disorders, announced that the US Food and Drug Administration (FDA) has approved Ztalmy (ganaxolone) oral suspension for the treatment of seizures associated with cyclin-dependent kinase-like 5 deficiency disorder (CDD), a rare form of genetic epilepsy, in patients two years of age and older.

Ztalmy, the first FDA approved treatment specifically in CDD, is a neuroactive steroid that acts as a positive allosteric modulator of the GABAA receptor. It is expected to be available through a designated specialty pharmacy in July 2022.

Clinical Basis of Approval

The approval of Ztalmy in CDD is based on 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% reduction in 28-day major motor seizure frequency, compared to a median 6.9% reduction for those receiving placebo, achieving the trial’s primary endpoint (p=0.0036). In the Marigold open label extension study, patients treated with Ztalmy for at least 12 months (n=48) experienced a median 49.6% 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% and at least twice the rate of placebo) in the Ztalmy group being somnolence, pyrexia, salivary hypersecretion and seasonal allergy.

Ztalmy is expected to be commercially available in the US in July following scheduling by the US Drug Enforcement Administration. To support the CDD community, Marinus plans to launch The Ztalmy One Programme, a comprehensive patient services programme to provide assistance with product access, ongoing support to patients, caregivers and their medical teams, and financial support to eligible patients.

The FDA reviewed Ztalmy under Priority Review and granted Ztalmy orphan drug and Rare Paediatric Disease designations for the treatment of CDD. With the approval, the FDA awarded a Rare Pediatric Disease Priority Review Voucher (PRV), which Marinus plans to monetize.

Ztalmy is the first and only FDA-approved treatment indicated specifically for seizures associated with cyclin-dependent kinase-like 5 deficiency disorder (CDD) in patients two years of age and older. Ztalmy, a neuroactive steroid that acts as a positive allosteric modulator of the GABAA receptor, is taken three times daily. It is expected to be available in July following scheduling by the US Drug Enforcement Administration.

Ztalmy is indicated for the treatment of seizures associated with cyclin-dependent kinase like 5 (CDKL5) deficiency disorder (CDD) in patients 2 years of age and older.