dm+d

Unassigned

New Medicines

ZtalmyTreatment of seizures associated with CDKL5 deficiency disorder in children and young adults aged 2 to 21 years

Information

Ztalmy
New molecular entity
Orion Pharma
Marinus Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Launched
Yes
Yes
Aug 22Earlier this year, the EMA assessment of the MAA for ganaxolone converted to a standard review. The company reached an agreement with the EMA to extend the Day 120 clock stop by three months to allow sufficient time to respond to questions received as part of the review process. The company expects the CHMP opinion by year end 2022 [19].
Jul 22Launched in US [18].
Mar 22In the US, Ztalmy has been priced at $2,425 per bottle, or $133,000 per year for the average sized patient (4.5 years old) [16]
Mar 22Approved by the FDA for the treatment of seizures associated with cyclin-dependent kinase-like 5 deficiency disorder (CDD) in patients two years of age and older [15]
Aug 21Pre-registration in the EU [14].
Aug 21Marinus enters into an agreement with Orion Corporation, in which Orion received exclusive rights to commercialise the oral and IV dose formulations of ganaxolone in Europe, UK and Switzerland [13].
Aug 21CHMP of the EMA grants accelerated assessment to ganaxolone for treatment of seizures associated with CDD [11].
Aug 21EU filing expected by the end of Q3 2021 with plans to launch mid 2022 [10].
Aug 21Filed in US for treatment of seizures associated with CDKL5 deficiency disorder; NDA includes a request for Priority Review. Rights to commercialise the oral and IV formulations of ganaxolone in Europe, UK and Switzerland for CDKL5 deficiency disorder, tuberous sclerosis complex and refractory status epilepticus have been transferred to Orion [8,9].
Sep 20Marinus plan to submit a NDA to US FDA mid-2021 and a MAA to EMA for ganaxolone for the treatment of CDD Q3 2021 [6].
Jul 20 FDA grants rare paediatric disease (RPD) designation for ganaxolone for the treatment of CDKL5 deficiency disorder (CDD) [7].
Dec 19Granted orphan drug status in EU [5].
Jun 17Granted orphan drug status in US [3].

Category

GABA A receptor agonist
CDKL5 deficiency disorder (CDD) is cone of most common forms of genetic epilepsy, caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome. It is estimated to occur in ~1:40,000 -75,000 live births. Affected individuals experience seizures at a very early age, (usually about 3 months but can be as early as the first week of life) and severe neurodevelopmental delay impacting cognitive, motor, speech, and visual function [1,2].
Treatment of seizures associated with CDKL5 deficiency disorder in children and young adults aged 2 to 21 years
Oral

Further information

Yes

Trial or other data

Apr 22Results of PIII NCT03572933 trial (n=101) reported in The Lancet [17].
Jun 21NICE decides ganaxolone is appropriate for potential highly specialised technologies (HST) guidance development and the topic passed to scoping team to prepare for a consultation exercise [12].
Sep 20PIII NCT03572933 trial (n=101)achieves primary endpoint. Patients receiving oral ganaxolone showed a 32% reduction in 28-day major motor seizure frequency vs. 4% reduction with placebo (p=0.002), at 17 weeks [6].
Jun 18Recruitment to PIII trial NCT03572933 begins [4].

Evidence based evaluations

ZtalmyTuberous sclerosis complex in adults and children - add-on therapy for inadequately controlled seizures

Information

Ztalmy
Licence extension / variation
Orion Pharma
Marinus Pharmaceuticals

Development and Regulatory status

None
None
Phase III Clinical Trials
Yes
Yes

Category

First-in-class CNS-selective, positive allosteric modulator of GABAA (gamma-aminobutyric acid). Ganaxolone acts on a well-characterised synaptic and extrasynaptic GABAA target known for anti-seizure, antidepressant and anti-anxiety activity, and it is a derivative of the naturally occurring neuromodulator allopregnanolone. Will be available in an oral suspension.
The incidence at birth is estimated to be 1 in 5,800. Tuberous sclerosis is very variable in both the organs involved and severity. Any organ system can be involved, with some more prevalent during infancy and childhood and others more likely to affect adults [1].
Tuberous sclerosis complex in adults and children - add-on therapy for inadequately controlled seizures
Oral