Angelini Pharma, an international pharmaceutical company part of the privately held Italian Angelini Group announced on 4 April 2022 that ONTOZRY® (cenobamate) is now available in the Netherlands for the adjunctive treatment of focal-onset seizures with or without secondary generalisation in adults patients who have not been adequately controlled despite an history of treatment with at least two anti-epileptic medicinal products. The product obtained approval from The European Medicines Agency in March ’21.2
There are an estimated 84 000 people in the Netherlands with epilepsy. Approximately 40% of adult patients with focal epilepsy have inadequate control of seizures after treatment with two anti-seizure medications (ASMs).3
Safety and efficacy of this product has been evaluated in three key trials involving over 1,900 patients.1,4,5 The pivotal trial (study 017) published in The Lancet Neurology1 is a multicenter, double-blind, randomised, placebo-controlled trial has 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. 1
The product 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% in the placebo arm. Furthermore, 4% (not significant), 11% (p=0.002), and 21% (p<0.001), of patients treated with this product 100 mg, 200 mg and 400 mg per day, respectively, reported zero focal-onset seizures (100% seizure freedom) compared with only 1% of placebo treated patients during the maintenance phase.1
The global disease burden of epilepsy is high.6,7 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 .6,8
In addition, people with epilepsy whose seizures are poorly controlled have higher morbidity and mortality rates, and often experience comorbid illnesses, social stigmatization, and an impaired quality of life.9,10
The product, which was discovered by SK Biopharmaceuticals and SK life science that have partnered with Angelini Pharma for the European market, marks a therapeutic breakthrough in managing the disease, and bringing hope to patients living with epilepsy.11
- Krauss GL et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicenter, double-blind, randomised, placebo-controlled, dose-response trial. Lancet Neurol. 2020 Apr;19(4):288-289.
- ONTOZRY SmPC
- Chen Z, et al. JAMA Neurol. 2018;75(3):279–286.
- Chung SS et al. Neurology. 2020;94(22):e2311–e2322.
- Sperling MR et al. Epilepsia. 2020;61(6):1099–1108
- Epilepsy: a public health imperative. Geneva: World Health Organization; 2019. Licence: CC BY-NC-SA 3.0 IGO.
- ILAE/IBE/WHO. Global Campaign Against Epilepsy: Out of the Shadows. 2003.
- Kaiser S, et al. Long-term follow-up of topiramate and lamotrigine: a perspective on quality of life. Seizure. 2002;11:356–360.
- Engel J. Bringing epilepsy out of the shadows. Neurol. 2003;60(9):1412.
- Engel J. Approaches to refractory epilepsy. Ann Indian Acad Neurol. 2014;17(Suppl 1):S12–7.
- Specchio N, et al. Int. J. Mol. Sci. 2021, 22, 9339.
- Cenobamate prescribing information. FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212839s000lbl.pdf Last accessed: January 2022.
- Guignet Met al, Epilepsia. 2020 Oct 16. doi: 10.1111/epi.16718.
- Anderson LL et al., Epilepsia 2014; 55(8):1274-1283.
- Stafstrom CE, Epilepsy Curr 2007; 7(1):15-22.
- Vreugdenhil M et al., Eur J Neurosci., 2004; 19: 2769-2778.
- White HS et al, Epilepsy Res. 1997;28(3):167-79.
18 ClinicalTrials.gov. NCT03678753
About Angelini Pharma
Angelini Pharma is an international pharmaceutical company, part of the Italian privately-owned Angelini Group with a UK affiliate established in 2021. Angelini Pharma is committed to helping patients in the therapeutic areas of Mental Health (including Pain), Rare Diseases and Consumer Healthcare. In particular, Angelini Pharma is committed to brain health – working every day to reduce and mitigate neurological disorders, while restoring and protecting mental health and cognitive function.
Over the past 50 years, in the field of mental health, Angelini Pharma has gained international recognition for its substantial efforts to improve the management of patients with mental health disorders thanks to important, internally developed molecules (such as trazodone) and its commitment to fighting mental-health stigma.
Angelini Pharma operates directly in 15 countries employing almost 3,000 people and commercialises its products in more than 50 countries through strategic alliances with leading international pharmaceutical groups.
In January 2021, Angelini Pharma announced that they concluded a definitive merger agreement under which Angelini Pharma acquired Arvelle Therapeutics. As a result, Angelini Pharma has the exclusive license to commercialise cenobamate in the European Union and other countries in the European Economic Area (Switzerland and the UK).
Cenobamate was discovered and developed by SK Biopharmaceuticals and SK life science and is an FDA and EMA-approved ASM for the treatment of partial-onset seizures in adults (also known as focal-onset seizures). Cenobamate is commercially available in the US under the trademark XCOPRI®.12
Cenobamate is a novel small molecule that provides a dual, complementary mechanism of action aimed at treatment of seizures.13,14 Cenobamate at clinically relevant concentrations, acts both as a positive allosteric modulator of GABAA receptors at a non-benzodiazepine binding site and preferentially blocks the persistent sodium current.9,14 The dual mechanism of action of cenobamate suggests that it has the potential to both prevent seizure initiation and limit seizure spread.15;16,17
Long-term data of cenobamate is being studied in the open-label extensions of the double-blind placebo control trials as well as the open-label safety study in adults with uncontrolled focal-onset seizures.5 Additionally, the product is being assessed in an ongoing randomised, double-blind, placebo-controlled trial evaluating its safety and efficacy as adjunctive therapy in patients with primary generalised tonic-clonic seizures. (NCT03678753)18
Cenobamate has recently gained recognition by healthcare regulatory bodies in the United Kingdom and Germany given its potential use in treatment resistant focal-onset seizures in epilepsy. The drug is available in Europe including Germany, Sweden, Denmark, UK and the Netherlands under the trademark ONTOZRY®.