RARE Daily

Marinus Wins FDA Approval for Therapy to Treat Rare Genetic Epilepsy

March 21, 2022

The U.S. Food and Drug Administration granted marketing approval to Marinus Pharmaceuticals for Ztalmy, an oral suspension for the treatment of seizures associated with cyclin-dependent kinase-like 5 deficiency disorder, a rare form of genetic epilepsy, in patients two years of age and older.

Photo: Karen Utley, president and co-founder of the International Foundation for CDKL5 Research

Cyclin-dependent kinase-like 5 deficiency disorder (CDD) is a serious and rare genetic disorder characterized by early‑onset, difficult‑to‑control seizures and severe neuro‑developmental impairment. It’s caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome. The CDKL5 gene produces a protein that is important for normal brain development and function.

Ztalmy is the first and only FDA-approved treatment indicated specifically for seizures associated with CDD in patients two years of age and older. Ztalmy, a neuroactive steroid that acts as a positive allosteric modulator of the GABAA receptor, is taken three times daily. It is expected to be available in July. Marinus plans to launch a comprehensive patient services program to assist with product access, ongoing support to patients, caregivers and their medical teams, and financial support to eligible patients.

The approval of Ztalmy in CDD is based on data from the phase 3 Marigold double-blind placebo-controlled trial, in which 101 patients were randomized and individuals treated with Ztalmy showed a median 30.7 percent reduction in 28-day major motor seizure frequency, compared to a median 6.9 percent reduction for those receiving placebo, achieving the trial’s primary endpoint. In the Marigold open label extension study, patients treated with Ztalmy for at least 12 months experienced a median 49.6 percent reduction in major motor seizure frequency.

In the clinical development program, Ztalmy demonstrated efficacy, safety, and tolerability with the most common adverse reactions (incidence >/5 percent and at least twice the rate of placebo) in the Ztalmy group being somnolence, pyrexia, salivary hypersecretion, and seasonal allergy.

The FDA reviewed Ztalmy under Priority Review and granted Ztalmy orphan drug and Rare Pediatric Disease designations for the treatment of CDD. With the approval, the FDA awarded a Rare Pediatric Disease Priority Review Voucher, which Marinus plans to monetize. The vouchers can be used to reduce the time of an FDA new drug approval review to six months from ten months. The vouchers are potentially lucrative because they are transferable. Most recently, BioMarin Pharmaceutical sold its voucher for $110 million.

“As the mother of a daughter living with CDD, I’ve experienced first-hand the devastating impact seizures can have on these patients,” said Karen Utley, president and co-founder of the International Foundation for CDKL5 Research. “This approval is monumental for the CDD community—bringing not only the first approved treatment option specifically for CDD patients, but renewed hope to those who have struggled to find medications that are effective in significantly reducing the number of seizures these patients experience on a daily basis.”

Author: Rare Daily Staff

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