Epilepsy drug developer Marinus Pharmaceuticals now has the first FDA Approvedthe decision also marks the first approved treatment for the rare genetic form of epilepsy.
The FDA on Friday approved the drug ganaxolone to treat cyclin-dependent kinase-like 5 (CDKL5) deficiency in patients 2 years and older.Radnor, Pennsylvania-based Marinus will market its new products under the following names: Ztalmi.
Patients with CDKL5 deficiency experience uncontrolled seizures and severe neurodevelopmental impairment. The disease arises from mutations in the CDKL5 gene, which encodes a protein critical for normal brain development and function. This gene is located on the X chromosome; CDKL5 deficiency disproportionately affects females. Children with this disorder have problems walking, talking, and taking care of themselves. Marinus estimates that 12,500 patients in the United States and Europe have CDKL5 deficiency.
Ztalmy is a small molecule designed to bind and activate type A GABA receptors in the central nervous system. This approach is designed to provide an anticonvulsant effect. Marinus medicine is formulated as an oral suspension to be taken 3 times a day with a meal.
Marinus evaluated Ztalmy in a clinical trial that enrolled 101 patients aged 2 years and older who had a confirmed CDKL5 gene mutation and who were not adequately controlled by at least two prior treatments Seizures. Nearly 80% of trial participants were women, which is consistent with the demographics of the disease. The primary objective of the double-blind and placebo-controlled Phase 3 study was to measure the reduction in seizure frequency over a 17-week treatment period. The results showed that patients who received Ztalmy had a median 28-day reduction in seizure frequency by 31 percent, compared with a median reduction of 7 percent in the placebo group. The FDA warns that the drug can cause drowsiness and sedation, an increased risk if the drug is used with alcohol. The agency also noted that patients taking the drug should be monitored for suicidal behavior and thoughts.
The dose of Ztalmy is based on body weight.according to a Marinus Investor Presentation, the average daily dose for a four-and-a-half-year-old patient weighing 16 kg (about 35.2 lbs) was 50 to 55 mg/kg. The wholesale cost of a vial of the drug is $2,425, and before any rebates or discounts, the average wholesale cost is about $133,000 per year. Marinus said in an investor presentation that it had committed to no price increases until the end of 2023.
Ganaxolone is a controlled substance and drug labels warn that use of this product may lead to abuse or dependence. The drug is subject to review by the U.S. Drug Enforcement Administration, which schedules the drug based on abuse and dependence risk. Marinus expects Ztalmy to launch in July after the DEA schedules.
CDKL5 deficiency is the first of several potential epilepsy indications for Ztalmy. A third phase is underway to test the drug in another rare genetic form of epilepsy called tuberous sclerosis complex. The company is also developing a new formulation for the treatment of Lennox-Gastaut syndrome.
Marinus reported a cash position of $122.9 million at the end of 2021. Following Ztalmy’s approval, the FDA also granted the company a Priority Review Voucher. Marinus said it plans to sell the vouchers; $100 million or more of such vouchers have been sold.
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