ONTOZRYTM (cenobamate) receives positive CHMP opinion for the adjunctive treatment of uncontrolled focal onset seizures in adults*

ONTOZRY^TM (cenobamate) receives positive CHMP opinion for the adjunctive treatment of uncontrolled focal onset seizures in adults*

Positive CHMP opinion is an important milestone for Arvelle Therapeutics and cenobamate

When approved, cenobamate will provide new hope in helping adult patients with uncontrolled focal epilepsy move closer to the goal of seizure reduction and seizure freedom

Zug, Switzerland, 29 January 2021 Arvelle Therapeutics, an emerging biopharmaceutical company focused on bringing innovative treatments to patients suffering from central nervous system (CNS) disorders, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of cenobamate for the adjunctive treatment of focal onset seizures with or without secondary generalization in adult patients with epilepsy who have not been adequately controlled despite a history of treatment with at least 2 anti-epileptic products.

The European Commission (EC), which is authorized to approve medicines in the European Union, is expected to issue its decision within 67 days of receipt of the CHMP opinion.

There are an estimated six million people in Europe with epilepsy[i] and approximately 40% of adult people with epilepsy have inadequate control of seizures after treatment with two anti-seizure medications (ASMs).[ii]

Mark Altmeyer, President and CEO, Arvelle Therapeutics, said, “Despite the number of ASMs that are currently available, a large proportion of patients continue to have seizures which can have devastating effects on them and their families’ lives. Cenobamate has been shown to significantly improve seizure control for focal-onset seizures in adult patients and this positive CHMP opinion means that patients may soon have a new treatment option” he added.

In January 2021, Angelini Pharma announced that they concluded a definitive merger agreement under which Angelini Pharma will acquire Arvelle Therapeutics. As a result, Angelini Pharma will have the exclusive license to commercialize cenobamate in the European Union and other countries in the European Economic Area (Switzerland and the United Kingdom). Angelini plans to launch cenobamate after receiving approval from the EC which is expected by Q2 2021.

“Positive CHMP opinion of cenobamate represents an important milestone for Angelini Pharma and for patients. Cenobamate showed significant efficacy, with more patients achieving a 50% or greater reduction in seizure frequency and unprecedented rates of seizure freedom of up to 21% compared to placebo. We are impressed and excited about what Arvelle Therapeutics’ people have achieved and built since we share the same vision” said Pierluigi Antonelli, CEO Angelini Pharma “The acquisition of Arvelle Therapeutics will propel us into a leading European player, well positioned to address the needs of patients with different Central Nervous System (CNS) disorders through an innovative portfolio, medical capabilities and extensive commercial presence. The agreement will be completed in the first week of February”.

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

Dr. Jeong Woo Cho, CEO of SK Biopharmaceuticals, said, “The positive CHMP opinion brings us all toward achieving a major milestone that will enable patients in Europe to access cenobamate, which has been 20 years in the making, once approved, SK Biopharmaceuticals will ensure, with its European partners, a launch of this medicine to the epilepsy community.”

The CHMP positive opinion was based on three trials involving over 1,900 patients. The main trial (study 017) published in The Lancet Neurology[iii] was a multicentre, double-blind, randomized, placebo-controlled trial that demonstrated that cenobamate is an effective treatment option 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 frequency) across all doses during the 12-week maintenance phase compared to placebo. The ≥50% responder rates were 40% (p=0.036), 56% (p<0.001), and 64% (p<0.001), for the 100 mg/day, 200 mg/day, and 400 mg/day cenobamate groups, respectively, compared to 25% for placebo. Furthermore, 4% (not significant, p=0.369), 11% (p=0.002), and 21% (p<0.001), of patients treated with cenobamate 100 mg, 200 mg, and 400 mg, respectively, reported 100% reduction in seizure frequency (100% seizure freedom) compared with only 1% of placebo-treated patients during the maintenance phase.³

The global disease burden of epilepsy is high.[iv]^,[v] A diagnosis of epilepsy may confer significant disability on the individual, including physical, psychological and social problems that could negatively impact self-esteem, family, relationships, leisure, work, career prospects and ability to drive.^4,[vi]

In addition, people with epilepsy whose seizures are poorly controlled have higher morbidity and mortality rates and often experience comorbid illnesses, social stigmatisation, psychological dysfunction and a reduced quality of life.[vii]^,[viii]

*Cenobamate was recommended as adjunctive treatment of focal onset seizures with or without secondary generalization in adult patients with epilepsy who have not been adequately controlled despite a history of treatment with at least 2 anti-epileptic products

[i]. Epilepsy Alliance Europe. Background information.  https://www.epilepsyallianceeurope.org/about/background/ Last

    accessed 03.12.2020.

[ii]. Chen Z et al. JAMA Neurol. 2018 Mar 1;75(3):279-286.

[iii]. Krauss GL et al. Lancet Neurol. 2020 Apr;19(4):288-289.

[iv]. Epilepsy: a public health imperative. Geneva: World Health Organization; 2019. Licence: CC BY-NC-SA 3.0 IGO.

[v]. ILAE/IBE/WHO. Global Campaign Against Epilepsy: Out of the Shadows. 2003.

[vi]. Kaiser S, et al. Seizure. 2002;11:356–360.

[vii]. Engel J. Neurol. 2003;60(9):1412.

[viii]. Engel J. Ann Indian Acad Neurol. 2014;17(Suppl 1):S12–7.