ONTOZRY® (cenobamate) receives European Commission approval for the treatment of drug-resistant focal-onset seizures in adults

ROME, March 30, 2021 /PRNewswire/ -- Angelini Pharma, an international pharmaceutical company part of the privately held Italian Angelini Group that has recently acquired the biopharmaceutical company Arvelle Therapeutics, announced today that the European Commission (EC) has granted marketing authorization for ONTOZRY^® for the adjunctive treatment of focal-onset seizures with or without secondary generalization in adults patients who have not been adequately controlled despite an history of treatment with at least two anti-epileptic medicinal products.

The EC marketing authorization is valid in all European Union Member States plus Iceland, Norway and Liechtenstein.

"ONTOZRY^® will be a welcome new treatment option in Europe for adults who have not yet been able to control their focal-onset seizures with available treatments. Treatment-resistant epilepsy has a devastating effect on patients and their families, and we are proud to help address this urgent health challenge," said Pierluigi Antonelli, CEO, Angelini Pharma. "Angelini Pharma looks forward to bringing ONTOZRY^® to patients across Europe and will continue to address the needs of patients with central nervous system disorders through our innovative product portfolio and pipeline."

"This approval marks a breakthrough in the treatment of focal-onset seizures in adults with epilepsy. It is very important that patients have a new treatment option because most of them continue to have seizures that can have devastating effects on their lives," said Agnese Cattaneo, Chief Medical Officer, Angelini Pharma. "There are an estimated six million people in Europe with epilepsy^[1] and approximately 40% of adult patients with focal epilepsy have inadequate control of seizures after treatment with two anti-seizure medications (ASMs)^[2]. The EC approval of cenobamate gives them all hope for a better life."

"Antiseizure medications introduced during the last three decades have improved our ability to tailor treatment choice to individual needs but have had little impact on seizure outcomes in people with refractory epilepsy," commented Emilio Perucca Professor of Clinical Pharmacology, University of Pavia, and Immediate Past President, International League against Epilepsy. "Cenobamate differs from these medications because its use results in unprecedented seizure freedom rates for these patients. This is important because only freedom from seizures can permit a return to a normal and fully productive life."

The EC approval is based on three key trials involving over 1,900 patients. The pivotal trial (study 017) published in The Lancet Neurology^[3] is a multicentre, double-blind, randomized, placebo-controlled trial that demonstrated that cenobamate at doses of 100 mg, 200 mg, and 400 mg/day significantly improved seizure control versus placebo for adult patients with focal-onset seizures taking 1-3 ASMs.

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 the placebo arm. 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.^[3]

The global disease burden of epilepsy is high.^[4],[5] A diagnosis of epilepsy confers significant disability on the individual, including physical, psychological and social issues that negatively impact self-esteem, family environment, relationships, leisure and working life.^[4],[6]

In addition, people with epilepsy whose seizures are poorly controlled have higher morbidity and mortality rates and often experience comorbid illnesses, social stigmatisation and an impaired quality of life.^[7],[8]

Cenobamate, which was discovered by SK Biopharmaceuticals and SK life science, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of partial-onset (focal) seizures in adults in 2019, and it is commercially available in the U.S. under the brand name XCOPRI^® (cenobamate tablets) CV.

"The approval by the European Commission is another major milestone in our efforts to increase access to cenobamate and to support patients with a much-needed new treatment option," said Jeong Woo Cho, PhD, President and CEO of SK Biopharmaceuticals and SK life science. "As a fully-integrated global pharmaceutical company, we are committed to discovering, developing and delivering new treatment options for epilepsy and other central nervous system disorders to people around the world."

1. Epilepsy Alliance Europe. Background information. https://www.epilepsyallianceeurope.org/about/background/. Last accessed 03.12.2020.
2. Chen Z et al. JAMA Neurol. 2018 Mar 1;75(3):279-286.
3. Krauss GL et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicenter, double-blind, randomized, placebo-controlled, dose-response trial. Lancet Neurol. 2020 Apr;19(4):288-289.
4. Epilepsy: a public health imperative. Geneva: World Health Organization; 2019. Licence: CC BY-NC-SA 3.0 IGO.
5. ILAE/IBE/WHO. Global Campaign Against Epilepsy: Out of the Shadows. 2003.
6. Kaiser S, et al. Long-term follow-up of topiramate and lamotrigine: a perspective on quality of life.
   Seizure. 2002;11:356?360.
7. Engel J. Bringing epilepsy out of the shadows. Neurol. 2003;60(9):1412.
8. Engel J. Approaches to refractory epilepsy. Ann Indian Acad Neurol. 2014;17(Suppl 1):S12?7.

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