The pivotal trial included 101 children and young
adults with CDD1,2

Patients in the randomized, placebo-controlled pivotal trial ranged in age from 2 to 19 years. Approximately 79% of these patients were female, 92% were white, and the mean age was 7.3 years.1,3

Baseline characteristics

Patients had tried and discontinued a median
of 7 ASMs (range: 1 to 16)3

Patients were taking an average of
2.4
concomitant ASMs3*

Patients had a median of 50 major motor
seizures per 28 days3

* 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

Patients taking ZTALMY experienced a significant reduction in seizure frequency1

ZTALMY reduced the frequency of monthly major motor seizures by a median of 31%, compared with 7% for placebo, over 17 weeks (P=0.0036).1

Chart showing seizure reduction of ZTALMY versus placebo Chart showing seizure reduction of ZTALMY versus placebo

Multiple major motor seizure types associated with CDD were measured1

  • Bilateral tonic
  • Generalized tonic-clonic
  • Atonic
  • Bilateral clonic
  • Focal to bilateral tonic-clonic

Seizure frequency was reduced by at least half for some patients1,2

More patients in the ZTALMY group (24.5%) experienced a ≥50% reduction from baseline in monthly major motor seizure frequency over 17 weeks compared with placebo (9.8%).3

Proportion of patients seeing a reduction in 28-day major motor seizure frequency ZTALMY versus placebo Proportion of patients seeing a reduction in 28-day major motor seizure frequency ZTALMY versus placebo

Pivotal trial design: The Marigold study1-4

The efficacy and safety of ZTALMY to treat seizures associated with CDD in patients 2 years of age and older were established in a single, double-blind, randomized, placebo-controlled study.1

Patients enrolled in the study were required to have1:

  • Molecular confirmation of a pathogenic or likely pathogenic cyclin-dependent kinase-like 5 (CDKL5) variant
  • Seizures inadequately controlled by at least 2 previous ASM regimens
  • A minimum of 16 major motor seizures per 28 days during the
    2 months prior to screening
Study design for the Marigold study

The 17-week double-blind phase of the Marigold study was followed by a long-term open-label phase in which all patients received ZTALMY. The primary objective of the open-label phase was to collect additional safety and tolerability data; additional efficacy assessments were also performed.2,4

*Total daily dosage divided 3 times a day.

Preliminary results from an open-label extension study
of patients taking ZTALMY

Following the pivotal trial, 88 out of 101 patients entered an open-label extension study to evaluate the ongoing safety and efficacy of ZTALMY. Safety findings in the OLE were consistent with the double-blind phase; no new safety findings had emerged at the time of analysis.3,4

Open-label design and small sample size preclude conclusions about efficacy.

Reduction in monthly major motor seizure frequency over 24 months in OLE3*

Median percent reduction in 28-day major motor seizure frequency, open-label ZTALMY versus placebo
Median percent reduction in 28-day major motor seizure frequency, open-label ZTALMY versus placebo

Seizure reductions were observed in patients who remained on ZTALMY in the OLE3

All patients had the opportunity to remain in the OLE for at least 1 year (minimum duration of follow-up). 34 (38.6%) patients discontinued from the OLE primarily due to lack of efficacy (n=12), adverse event (n=10), and withdrawal by subject or parent/LAR (n=10). LOCF analyses showed similar findings during the minimum duration of follow-up in the OLE.3

LOCF=last observation carried forward.

LAR=legally authorized representative.

*Date of analysis: June 22, 2021.

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Learn about the
safety data
for ZTALMY

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. ZTALMY [package insert]. Radnor, PA: Marinus Pharmaceuticals, Inc.; 2022.
  2. Knight EMP, Amin S, Bahi-Buisson N, et al. Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2022;21(5):417-427.
  3. Data on file. Marinus Pharmaceuticals, Inc.
  4. Specchio N, Amin S, Hulihan J, et al. Extended duration safety and efficacy of ganaxolone for the treatment of CDKL5 deficiency disorder: preliminary open-label extension analysis (Marigold Study). American Epilepsy Society. Dec 4-8, 2020. Virtual conference.