Controlling epileptic seizures associated with a rare genetic condition, CDKL-5 deficiency disorder (CDD), has been a difficult problem to tackle.
But Marinus Pharmaceuticals has developed a treatment that has cracked the code. Friday, the company's Ztalmy, a three-times-daily oral therapy, became the first FDA-approved med for CDD.
The Radnor, Pennsylvania-based company expects Ztalmy, also known as ganaxolone, to be available in July. The FDA nod is for CDD patients 2 years and older.
The disorder was first identified in 2004. It typically triggers seizures within the first few months of a baby’s life that could lead to severe neurodevelopmental impairment. It is caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL-5) gene, located in the X chromosome, which produces a protein that is key for normal brain development and function.
Once the drug showed promise, the FDA granted Ztalmy priority review and orphan drug designations. Upon approval, the FDA handed Marinus a potentially lucrative Pediatric Disease Priority Review Voucher, which the company said it plans to monetize.
"We have seen recent voucher sales in excess of $100 million," Marinus CFO Steve Pfanstiel said in a conference call on Monday. "I would anticipate we could execute an agreement in Q2."
Pfanstiel added that the approval allows Marinus to draw an additional $30 million because of a credit agreement with Oaktree Capital Management. The agreement could provide up to $125 million ii credit by the end of 2023.
Ztalmy has been priced at $2,425 per bottle, or $133,000 per year for the average sized patient, chief commercial officer Christy Shafer said on the call. Marinus has pegged the average patient age at 4.5 years, but expects that could rise to age 11 over time as the treatment demonstrates success.
The FDA’s green light was based on data from the Marigold phase 3 study of 101 patients that showed those on Ztalmy had a 31% reduction in 28-day major motor seizure frequency versus a 7% decline in those receiving placebo.
In an open-label extension study, patients treated with Ztalmy for at least 12 months saw a median 50% reduction in major motor seizure frequency.
“To date, antiseizure treatment decisions have been based on very limited clinical evidence in this patient population, and the resulting outcomes underscore the need for therapies that further improve seizure control,” Scott Demarest, M.D., the principal investigator for the Marigold trial, said in the release. “Thanks to our research and this trial, we now have the first treatment specifically approved for seizures associated with CDKL5.”
Ztalmy is a neuroactive steroid that acts as a positive allosteric modulator of the GABA receptor. It has shown potential to curb seizure frequency in patients with another rare condition—tuberous sclerosis complex—which causes benign tumors to grow in various parts of the body including the brain
There are other epilepsy indications Marinus is exploring with Ztalmy. The company is screening patients for a phase 3 trial testing its effectiveness on those with tuberous sclerosis complex (TSC). The company also is recruiting participants for trials in refractory status epilepticus and established status epilepticus.
In August of last year, Marinus revealed that it made a $30 million deal with Orion for European rights for the drug.
The treatment has made a successful comeback after being pulled from the scrapheap. In a phase 3 trial measuring the drug's effectiveness in controlling adult focal onset seizures, it failed to top placebo.