Paramus - SK Life Science, Inc., a subsidiary of SK Biopharmaceuticals Co., Ltd., an innovative global pharmaceutical company focused on developing treatments for central nervous system (CNS) disorders, announced Epilepsia has published interim results from an ongoing large, multi-center, open-label Phase 3 study assessing the long-term safety and tolerability of cenobamate, an anti-seizure medication (ASM), in adults with uncontrolled partial-onset (focal) seizures.
The study also assessed if a lower starting dose and every other week titration could mitigate the risk of DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms), seen in the early clinical development of cenobamate. The study demonstrated that adjunctive treatment with cenobamate was generally safe and well tolerated with long-term use, with 83% of patients taking cenobamate 6 months. No cases of DRESS were identified using this titration schedule.
In the study, 1,339 patients taking 1-3 other ASMs started cenobamate at 12.5 mg/day. Doses were increased every two weeks to 25, 50, 100, 150 and 200 mg/day, with additional increases up to 400 mg/day (50 mg increases every two weeks) as needed.
The most common treatment-emergent adverse events (TEAEs) reported were somnolence (28%), dizziness (24%), and fatigue (17%). TEAEs resulting in discontinuation occurred in 147 patients (11%). Serious TEAEs occurred in 108 patients (8%), with the most common event being seizure (n=19). No new safety issues were identified.
'These results support a low starting dose and increased titration every two weeks as the recommended way to start treatment with cenobamate, as it may reduce the risk of DRESS in adults with uncontrolled focal seizures,' said Marc Kamin, MD, Chief Medical Officer, SK life science. 'The ongoing Phase 3 study as well as the open-label extensions of the randomized studies will provide additional data on the longterm safety profile of adjunctive cenobamate.'
About Study 021
Study 021 is a large, multi-center, open-label Phase 3 study assessing the safety of cenobamate as adjunctive therapy in adults (18-70 years old) with uncontrolled focal seizures, taking 1-3 ASMs. The objectives of the study included the characterization of the long-term safety of cenobamate and to understand how to best add cenobamate to regimens that included phenytoin or phenobarbital. In addition, the study was designed to determine the rate of DRESS in at least 1,000 patients taking cenobamate for at least 6 months, using a low starting dose and every other week titration. Cenobamate was initiated at 12.5 mg/day and increased at 2-week intervals to 25, 50, 100, 150 and 200 mg/day. Further increases to 400 mg/day using bi-weekly 50 mg/day increments were allowed.
Cenobamate is an FDA-approved anti-seizure medication (ASM) for the treatment of partial-onset seizures in adults, which is now available in the U.S. under the brand name XCOPRI (cenobamate tablets) CV. It was discovered and developed by SK Biopharmaceuticals and SK life science. In early 2019, SK Biopharmaceuticals entered into an exclusive licensing agreement with Arvelle Therapeutics GmbH to develop and commercialize cenobamate in Europe.
While the precise mechanism by which cenobamate exerts its therapeutic effect is unknown, it is believed to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents. It is also a positive allosteric modulator of the -aminobutyric acid (GABAA) ion channel. Cenobamate should be initiated at 12.5 mg once-daily and titrated every two weeks; it is available in six tablet strengths for once-daily dosing: 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg and 200 mg. Cenobamate can be combined with other ASMs or used alone.
About SK Biopharmaceuticals Co., Ltd. and SK Life Science, Inc.
SK Biopharmaceuticals and its U.S. subsidiary SK life science are global pharmaceutical companies focused on the research, development and commercialization of treatments for disorders of the central nervous system (CNS). The companies have a pipeline of eight compounds in development for the treatment of CNS disorders, including epilepsy. Additionally, SK Biopharmaceuticals is focused on early research in oncology.
Both SK Biopharmaceuticals and SK life science are part of SK Group, one of the largest conglomerates in Korea. SK Holdings, the parent company of SK Biopharmaceuticals, continues to enhance its portfolio value by executing long-term investments with a number of competitive subsidiaries in various business areas, including pharmaceuticals and life science, energy and chemicals, information and telecommunication, and semiconductors. In addition, SK Holdings is focused on reinforcing its growth foundations through profitable and practical management based on financial stability, while raising its enterprise value by investing in new future growth businesses.