Most common adverse reactions in the pivotal trial

Adverse reactions that occurred over 17 weeks
(incidence ≥3% and greater than placebo)1

Adverse Reactions ZTALMY (n=50) Placebo (n=51)
Somnolence 38% 20%
Pyrexia 18% 8%0
Upper respiratory tract infection 10% 6%0
Sedation 6% 4%0
Salivary hypersecretion 6% 2%0
Seasonal allergy 6% 00%
Bronchitis 4% 00%
Influenza 4% 2%0
Gait disturbance 4% 2%0
Nasal congestion 4% 2%0

Somnolence includes the terms lethargy and hypersomnia.

The most frequent adverse reactions leading to a dose interruption or reduction in ZTALMY-treated patients were somnolence (10%) and sedation (2%).

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 with ZTALMY.1

Fewer patients taking ZTALMY discontinued treatment compared with placebo2

Incidence of discontinuation due to adverse reactions in the pivotal trial2

Incidence of discontinuation due to adverse reactions in the pivotal trial Incidence of discontinuation due to adverse reactions in the pivotal trial

of patients on ZTALMY

Incidence of discontinuation due to adverse reactions in the pivotal trial Incidence of discontinuation due to adverse reactions in the pivotal trial

of patients on placebo

The adverse reactions leading to discontinuation in the ZTALMY group were somnolence and seizure (1 patient) and seizure (1 patient).1

Withdrawal of antiepileptic drugs (AEDs)

As with most AEDs, withdraw ZTALMY gradually to minimize the risk of increased seizure frequency and status epilepticus. If withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.1

Most adverse events were mild or moderate in severity2

Summary of treatment-emergent AEs over 17 weeks2

Category ZTALMY (n=50) Placebo (n=51)
TEAEs* by severity†    
Mild 32% 52.9%
Moderate 52% 29.4%
Severe 2% 5.9%0

Note: If a subject experienced more than 1 adverse event in a category, the subject was counted only once in that category.2

*TEAE=Treatment-emergent adverse event, defined as an AE that occurred or worsened on the day of or after the first dose of study drug.2

✝︎Highest severity for subjects.2

Suicidal Behavior and Ideation

Antiepileptic drugs (AEDs), including ZTALMY, increase the risk of suicidal thoughts or behavior. Monitor patients taking ZTALMY for the emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior.1

About the study population

The pivotal trial was a double-blind, randomized, placebo-controlled study of 101 patients with CDD aged 2 to 19 years.1

  • Patients had tried and discontinued a median of 7 ASMs2
  • Patients were taking an average of 2.4 concomitant ASMs2*
  • Patients had a median of 50 major motor seizures per 28 days2

*96% of patients were taking at least 1 ASM. The most frequently used (≥20% of patients) concomitant ASMs were valproate, levetiracetam, clobazam, and vigabatrin.1

ZTALMY was administered concomitantly
with commonly used ASMs in CDD1,3,4

Percentage of patients taking ZTALMY receiving concomitant ASM treatment Percentage of patients taking ZTALMY receiving concomitant ASM treatment

of patients taking ZTALMY received concomitant ASM treatment2

The most common ASMs (used by ≥20% of patients) were2:

  • valproate
  • levetiracetam
  • clobazam
  • vigabatrin
Percentage of patients taking ZTALMY using other concomitant medications Percentage of patients taking ZTALMY using other concomitant medications

of patients taking ZTALMY used other concomitant medications2

The most common concomitant non-ASM medications were2:

  • acetaminophen (n=15)
  • polyethylene glycol (PEG) (n=5)

CYP3A4 inducers

Coadministration of ZTALMY with CYP450 inducers, such as strong or moderate CYP3A4 inducers, will decrease ganaxolone exposure, which can lower the efficacy of ZTALMY. When concomitant use of strong or moderate CYP3A4 inducers is unavoidable, consider an increase in the dosage of ZTALMY; however, do not exceed the maximum daily dosage of ZTALMY.1

Results from an open-label extension study

Following the pivotal trial, an open-label extension (OLE) study was conducted of patients taking ZTALMY. The primary objective of the study was to evaluate safety. No new safety signals were found. Reduction in seizure frequency was also measured.

SEE THE OLE DATA

Learn about the dosing and administration of ZTALMY

DOSING

Get patients started on ZTALMY

PRESCRIBING RESOURCES

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 (38%), pyrexia (18%), salivary hypersecretion (6%), and seasonal allergy (6%).

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. ZTALMY [package insert]. Radnor, PA: Marinus Pharmaceuticals, Inc.; 2023.
  2. Data on file. Marinus Pharmaceuticals, Inc.
  3. Olson HE, Demarest ST, Pestana-Knight EM, et al. Pediatr Neurol. 2019;97:18-25.
  4. Knight EMP, Amin S, Bahi-Buisson N, et al. Lancet Neurol. 2022;21(5):417-427.