Ganaxolone (Ztalmy) Approved by FDA for treating patients with seizure in CDD

Ganaxolone (Ztalmy) Approved by FDA for treating patients with seizure in CDD

By, Bala Krishnan P

In March 2022, FDA has approved Ztalmy (ganaxolone) to treat seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients >2 years of age. This is the first medication particularly for CDD as well as the first treatment for seizures linked to CDD.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder

CDD is a rare X-linked genetic disorder which was initially identified in 2004. CDKL5 stands for cyclin-dependent kinase-like 5, located on the X chromosome. The CDKL5 gene is responsible to make a protein required for normal brain development.

Features of CDD

• Seizure episodes beginning in the first three to six months of infancy (some may even start in the first week of life).
• Problems with development of the nervous system, including cognitive development.
• Stereotyped repetitive hand movements.

Ganaxolone

• Ganaxolone (GNX) is the 3β- methylated synthetic analog of allopregnanolone and an allosteric GABAA positive modulator. Ganaxolone belongs to a class- neurosteroids.
• The neurosteroids progesterone and allopregnanolone control numerous neuroprotective functions in neural tissues which includes inhibiting  epileptic seizures and cell death.
• Ganaxolone  helps in reducing the frequency of CDD-associated seizures

Mechanism of action

When treating seizures linked to CDD, the exact mode of action of ganaxolone is uncertain. Positive allosteric GABA-A modulation is most likely the cause of its anticonvulsant properties. Ganaxolone exerts its action by binding GABA-A at one of several potential binding sites, which enhances the inhibitory effects of GABA-A receptors. 

Adverse effects:

• Common:  somnolence (sleepiness), Excessive salivation (6% ),Fever, Seasonal allergy
• Serious: sedation, Suicidal behaviour, Suicidal thoughts

Safety information

• These risks increase if patients use ganaxolone with central nervous system depressants, such as alcohol. 
• Monitor patients for suicidal behavior and thoughts. When stopping the medication, patients should gradually reduce ganaxolone to minimize the risk of increased seizure frequency and status epilepticus.
• Dose adjustment is necessary for severe hepatic impairment patients.