FDA Approves First Therapy for Rare, Genetic Seizure Disorder

Ztalmy was approved for seizures associated with CDKL5 deficiency disorder in patients two years of age and older. It is expected to be available in July 2022.

The 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, developed by Marinus Pharmaceuticals, is the first FDA approved treatment specifically in CDD. It is a neuroactive steroid that acts as a positive allosteric modulator of the GABAA receptor.

Ztalmy is expected to be available through a designated specialty pharmacy in July 2022, according to executives with Marinus.

CDD is a serious and rare genetic disorder characterized by early‑onset, difficult‑to‑control seizures and severe neuro‑developmental impairment. It’s 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.

“There has been a great unmet medical need for treatments that address seizures associated with CDKL5 deficiency disorder given their prominent role and profound impact on patients,” Scott Demarest, M.D., principal investigator (PI) for the Marigold trial and neurologist and Clinical Director of Precision Medicine at Children’s Hospital Colorado, said in a press release. “To date, antiseizure treatment decisions have been based on very limited clinical evidence in this patient population and the resulting outcomes underscore the need for therapies that further improve seizure control.”

The approval is based on data from the phase 3 Marigold 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 with a median 6.9% reduction for those receiving placebo. In the Marigold open label extension study, patients treated with the therapy for at least 12 months experienced a median 49.6% reduction in major motor seizure frequency.