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Rare Seizure Disorder Gets Its First Drug Approval

— Ganaxolone wins FDA nod for patients 2 and older with CDD

Ƶ MedicalToday
FDA APPROVED Ganaxolone (Ztalmy) over a computer rendering of a blurry brain and brain waves.

Ganaxolone (Ztalmy) won approval to treat seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD), a rare genetic epilepsy, in patients ages 2 and older, the .

Ganaxolone is a neuroactive steroid that acts as a positive allosteric modulator of the GABAA receptor. The oral therapy is the first drug approved specifically for CDD, the FDA said.

CDD is a developmental encephalopathy caused by pathogenic variants in the CDKL5 gene. The CDKL5 protein is widely expressed in the brain, predominantly in neurons. The disorder includes early infantile onset refractory epilepsy and severe neurodevelopment impairment. Its incidence is estimated to be between one in 40,000-60,000 live births, making it one of the genetic forms of epilepsy.

The FDA nod was based on results of the randomized , which showed that CLL patients ages 2 to 19 treated with ganaxolone had a 30.7% median reduction in their 28-day frequency of major motor seizures, compared with a 6.9% reduction for those who received placebo (P=0.0036).

Somnolence, pyrexia, salivary hypersecretion, and seasonal allergy were the most common side effects experienced by participants taking ganaxolone in the trials.

"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," said Scott Demarest, MD, of Children's Hospital Colorado in Aurora, principal investigator for the Marigold trial, in a .

"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," Demarest noted.

With the FDA decision, "we now have the first treatment specifically approved for seizures associated with CDKL5 deficiency disorder that was shown to have a positive benefit-risk profile," he added.

Ganaxolone can cause sleepiness and sedation; these if patients also use central nervous system depressants like alcohol, the FDA warned. Healthcare providers should monitor patients for suicidal behavior and thoughts. If ganaxolone treatment is withdrawn, it should be done gradually.

Patients should not use ganaxolone if they are taking other treatments that act as moderate or strong cytochrome P450 (CYP) 3A4 inducers, like rifampin or St John's wort; these therapies may lower the efficacy of the drug, the agency added.

Ganaxolone is taken by mouth three times daily. It is expected to be available in July after Drug Enforcement Agency (DEA) , drugmaker Marinus Pharmaceuticals said.

  • Judy George covers neurology and neuroscience news for Ƶ, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more.