Early diagnosis can help families and care teams plan ahead2,3

Intractable seizures in infancy are typically the first overt symptom of CDD and signal the need for genetic testing, including the CDKL5 gene. A confirmed diagnosis of CDD is critical for decision-making about antiseizure medications and other interventions for overall CDD management.1,2,6

Minimum diagnostic criteria for CDD2*

Onset of epilepsy within the first year of life

Presence of pathogenic or likely pathogenic variant in the CDKL5 gene

Motor and cognitive developmental delays

Common clinical characteristics2

  • Early-onset and refractory epilepsy
  • Severe global developmental delay
  • Intellectual disability
  • Hypotonia
  • Cortical visual impairment
  • Sleep disturbance
  • Dyskinetic movements
  • Autonomic and breathing disturbances
  • GI disturbances (reflux, constipation)
  • Dysphagia

*Minimum diagnostic criteria for CDD is from expert opinion of Olson et al (2019).

Seizures persist throughout the patient journey
and are often refractory3,7

Seizures associated with CDD remain a lifelong concern that must be managed alongside the constellation of other symptoms and comorbidities. Patients typically cycle through multiple antiseizure medications with limited response.7-9

The burden of seizures in CDD

Daily seizures

Despite a majority taking at least 2 ASMs, patients experienced a median of 2 seizures a day10*

Treatment failure

Patients were prescribed a median of 6 ASMs (range: 0 to 18) over the course of their lives9✝

brain behind grid structure icon

Rarely seizure-free

Fewer than half of patients with CDD experienced >2 months of sustained seizure freedom10*

ASMs=antiseizure medications.

*Data from the international CDKL5 patient registry on 172 individuals with CDKL5 deficiency disorder, with a median age of 5 years, per caregiver report.10

✝︎Study analyzed 177 individuals with CDKL5 deficiency disorder, with a median age of 8.1 years.9

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EFFICACY
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SAFETY

IMPORTANT SAFETY INFORMATION AND INDICATION

WARNINGS AND PRECAUTIONS

  • Somnolence and Sedation: ZTALMY can cause somnolence and sedation. In a clinical study somnolence and sedation appeared early during treatment and were generally dose related. Other CNS depressants, including opioids, antidepressants, and alcohol, could potentiate these effects. Monitor patients for these effects and advise them not to drive or operate machinery until they have gained sufficient experience on ZTALMY to gauge whether it adversely affects their ability to drive or operate machinery.

IMPORTANT SAFETY INFORMATION AND INDICATION

INDICATION AND USAGE

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.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

The most common adverse reactions (incidence of at least 5% and at least twice the rate of placebo) were somnolence, pyrexia, salivary hypersecretion, and seasonal allergy.

DRUG INTERACTIONS

Cytochrome P450 inducers will decrease ganaxolone exposure. Avoid concomitant use with strong or moderate CYP3A4 inducers; if unavoidable, consider a dosage increase of ZTALMY, but do not exceed the maximum recommended dosage.

USE IN SPECIFIC POPULATIONS

DRUG ABUSE AND DEPENDENCE

ZTALMY contains ganaxolone, a Schedule V controlled substance (CV). Advise patients of the potential for abuse and dependence. It is recommended that ZTALMY be tapered according to the dosage recommendations unless symptoms warrant immediate discontinuation.

Please see full Prescribing Information.

References:

  1. Demarest ST, Olson HE, Moss A, et al. CDKL5 deficiency disorder: relationship between genotype, epilepsy, cortical visual impairment, and development. Epilepsia. 2019;60(8):1733-1742.
  2. Olson HE, Demarest ST, Pestana-Knight EM, et al. Cyclin-dependent kinase-like 5 deficiency disorder: clinical review. Pediatr Neurol. 2019;97:18-25.
  3. Jakimiec M, Paprocka J, Śmigiel R. CDKL5 deficiency disorder—a complex epileptic encephalopathy. Brain Sci. 2020;10(2):1-9.
  4. Symonds JD, Zuberi SM, Stewart K, et al. Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort. Brain. 2019;142(8):2303-2318.
  5. Mei D, Parrini E, Marini C, Guerrini R. The impact of next-generation sequencing on the diagnosis and treatment of epilepsy in paediatric patients. Mol Diagn Ther. 2017;21(4):357–373.
  6. Mangatt M, Wong K, Anderson B, et al. Prevalence and onset of comorbidities in the CDKL5 disorder differ from Rett syndrome. Orphanet J Rare Dis. 2016;11:1-17.
  7. Bahi-Buisson N, Bienvenu T. CDKL5-related disorders: from clinical description to molecular genetics. Mol Syndromol. 2012;2(3-5):137-152.
  8. Müller A, Helbig I, Jansen C, et al. Retrospective evaluation of low long-term efficacy of antiepileptic drugs and ketogenic diet in 39 patients with CDKL5-related epilepsy. Eur J Paediatr Neurol. 2016;20(1):147-151.
  9. Olson HE, Daniels CI, Haviland I, et al. Current neurologic treatment and emerging therapies in CDKL5 deficiency disorder. J Neurodev Disord. 2021;13(1):1-11.
  10. Fehr S, Wong K, Chin R, et al. Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder. Neurology. 2016;87(21):2206-2213.