Results of Randomized Study Evaluating the Safety and Efficacy of Cenobamate in Patients with Uncontrolled Focal-Onset Epilepsy Published in The Lancet Neurology
Cenobamate significantly reduced focal seizure frequency, with as many as 20% of patients reaching zero seizures during the study's maintenance phase
Zug, Switzerland, November 14, 2019 – Arvelle Therapeutics GmbH, an emerging biopharmaceutical company focused on bringing innovative treatments to patients with CNS disorders, today announced the publication in The Lancet Neurology of a key pivotal trial demonstrating that treatment with cenobamate significantly improved seizure control for partial-onset (focal) seizures in adult patients with epilepsy in this trial.
This multicentre, double-blind, randomized, placebo-controlled trial demonstrated that cenobamate at doses of 100 mg, 200 mg, and 400 mg/day significantly improved seizure control versus placebo in patients with focal-onset seizures taking 1-3 anti-epileptic drugs (AEDs). Cenobamate demonstrated significantly higher responder rates (percentage of patients achieving ≥50% reduction in seizures) across all doses during the 12-week maintenance phase compared to placebo. The responder rates were 40% (p=0.036), 56% (p<0.001), and 64% (p<0.001), for the 100 mg, 200 mg, and 400 mg groups, respectively, compared to 25% for placebo. Furthermore, 4% (not significant), 11% (p=0.002), and 21% (p<0.001), of patients treated with cenobamate 100 mg, 200 mg, and 400 mg, respectively, reported zero focal-onset seizures (100% seizure freedom) compared with only 1% of placebo-treated patients during the maintenance phase.1
Overall, most treatment-emergent adverse events (TEAEs) were mild or moderate in severity, and similar to those observed with other AEDs. The most common TEAEs reported were somnolence, dizziness, headache, fatigue and diplopia and the incidences increased with the dosage. One serious case of drug reaction with eosinophilia and systemic symptoms (DRESS) occurred in the 200 mg cenobamate group.1
Cenobamate is currently under review by the U.S Food and Drug Administration (FDA) with an expected outcome date (PDUFA target action date) of November 21, 2019.
There are an estimated six million people in Europe with epilepsy2 and approximately 40% of adult patients with focal epilepsy have inadequate control of seizures after treatment with 2 AEDs.3
Christian Brandt MD, Head of the Department of General Epileptology at Bethel Epilepsy Centre in Germany, said:
This pivotal trial published in The Lancet Neurology represents a key milestone in the development of epilepsy therapies for adult patients with focal-onset seizures. Both, the study results, as well as our own experiences during the clinical trials, suggest that cenobamate may play an important role in overcoming the ongoing burden for a significant number of patients who continue to have seizures despite the use of available treatments. These results are very encouraging for many patients with uncontrolled focal epilepsy.
Arvelle Therapeutics has licensed exclusive rights to develop and commercialize cenobamate in Europe. Arvelle Therapeutics intends to file a Marketing Authorization Application (MAA) for cenobamate as a treatment for focal-onset seizures in adult patients based on the data generated from SK Biopharmaceuticals' global clinical trial program, involving more than 1,900 patients.
Ilise Lombardo MD, Co-Founder and Chief Medical Officer at Arvelle Therapeutics, said:
The publication of these results is a critical step towards understanding the role cenobamate could play in focal-onset seizures. We will continue to partner with the epilepsy community in Europe as we work to bring this potential therapeutic option to patients.
For further information on the trial published in The Lancet Neurology, please click here.
Arvelle Therapeutics GmbH
Juan Vergez
Email: juan.vergez@arvelletx.com
Trio Health
Nick James (nick@triohealth.co.uk)
Nina Bass (nina@triohealth.co.uk)
Chloe Nichols (chloe@triohealth.co.uk)
About Study 017
Study 017 is a multicentre, double-blind, randomized, placebo-controlled, dose-response study to evaluate the safety and efficacy of cenobamate as an adjunctive therapy in adults (18 to 70 years old) with uncontrolled focal epilepsy despite treatment with 1-3 anti-epileptic drugs (AEDs).
Following an 8-week baseline period, the study participants were randomized to one of three doses of cenobamate (100 mg, 200 mg and 400 mg once daily) or placebo for 18 weeks (6-week titration phase and 12-week maintenance phase). The primary outcomes were median percentage seizure reduction over the entire study and 50% responder rate (percentage of patients achieving ≥50% reduction in seizures) during the maintenance phase. Patients who continued to meet study eligibility had the option to enrol in an open-label extension, the results of which will be presented at upcoming medical meetings and will provide additional insight into the long-term clinical and safety profile of adjunctive cenobamate.
Cenobamate (YKP3089) was discovered by SK Biopharmaceuticals and SK life science and is being investigated for the potential treatment of partial-onset seizures in adult patients.
Cenobamate is believed to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents and as a positive allosteric modulator of the GABAA ion channel.
Global trials for adults with partial-onset seizures are ongoing to evaluate cenobamate's long-term safety and additional clinical trials are investigating cenobamate in other seizure types.
The FDA accepted the filing of the New Drug Application for cenobamate for the potential treatment of partial-onset seizures in adults in February 2019. A Prescription Drug User Fee Act (PDUFA) target action date has been set for November 21, 2019. Cenobamate is not approved by the FDA or any other regulatory authorities. Safety and efficacy have not been established.
About Arvelle Therapeutics GmbH
Arvelle Therapeutics is an emerging biopharmaceutical company focused on bringing innovative solutions to patients with CNS disorders. Arvelle Therapeutics is responsible for the development and commercialization of cenobamate, an investigational anti-epileptic drug, in the European market. Arvelle Therapeutics is headquartered in Switzerland and received start-up financing of $207.5 million, one of the largest initial financing commitments for a European‐focused biopharmaceutical company, with investments from a global syndicate including Andera Partners, BRV Capital Management, F-Prime Capital, H.I.G. BioHealth Partners, KB Investments and NovaQuest Capital Management, LSP. More information is available at www.arvelletx.com.
About SK Biopharmaceuticals, Co., Ltd. and SK Life Science, Inc.
SK Biopharmaceuticals and its U.S. subsidiary SK life science are focused on the research, development and commercialization of treatments for disorders of central nervous system (CNS). Additionally, SK Biopharmaceuticals is focused on early research and development in oncology. Both are part of SK Group, one of largest conglomerates in Korea.
SK Holdings 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. For more information, please visit http://hc.sk.co.kr/en/.
Currently, SK Biopharmaceuticals is conducting basic research for the development of innovative new therapies at its research center in Pangyo, Gyeonggi Province, Korea. SK life science, based in Paramus, New Jersey, is pursuing clinical development and commercialization in the United States.
The companies have a pipeline of eight compounds in development for the treatment of CNS disorders including epilepsy, Lennox-Gastaut syndrome and attention deficit hyperactivity disorder, among others. For more information, visit SK Biopharmaceuticals' website at www.skbp.com/eng and SK life science's website at www.SKLifeScienceInc.com.
The Lancet Neurology, 13 November, 2019. http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(19)30399-0/fulltext
Epilepsy Alliance Europe. Background information. https://www.epilepsyallianceeurope.org/about/background/ Last accessed 08.11.2019
Chen Z et al. JAMA Neurol. 2018 Mar 1;75(3):279-286.