Angelini Pharma’s Cenobamate▼ receives approval in Ireland for use in adults with focal onset seizures in adult patients with epilepsy

Angelini Pharma’s Cenobamate▼ receives approval in Ireland for use in adults with focal onset seizures in adult patients with epilepsy

• Cenobamate (ONTOZRY®) for adjunctive treatment of focal onset seizures with or without secondary generalisation in adult patients with epilepsy who have not been adequately controlled despite a history of treatment with at least two anti-epileptic medicinal products
• Around 40,000 people in Ireland are currently living with epilepsy[1] and significant treatment needs remain for those with drug-resistant disease[2]
• Uncontrolled seizures have a high burden on quality of life and can impact many aspects of daily living, such as driving, going to work and completing everyday activities[3]
• Data show that over half of people taking cenobamate experienced a 50%-or-more reduction in focal (partial) seizure frequency[4]

London, UK, May 15 2023 – Angelini Pharma has today announced that cenobamate, an oral anti-seizure medicine (ASM), has been reimbursed for adjunctive treatment of focal onset seizures with or without secondary generalisation in adult patients with epilepsy who have not been adequately controlled despite a history of treatment with at least two anti-epileptic medicinal products.^[5]

In Ireland, 30% of people with epilepsy have difficulty controlling their seizures,[6] and are therefore more likely to experience comorbidities, social stigmatisation and have an impaired quality of life.³

The reimbursement of cenobamate follows the positive recommendation from the National Centre for Pharmacoeconomics (NCPE), and the approval in EU with the European Commission Decision granted on March 26^th, 2021. A pivotal clinical trial data (study C017) published in The Lancet Neurology, also demonstrated that drug-resistant focal-onset seizures showed 50%-or-greater reduction among more than half of patients when adding cenobamate (200 mg/day) to their daily treatment of 1–3 anti-seizure medications.⁴ Furthermore, 11.2% of patients were seizure-free when taking 200 mg/day of cenobamate, and this increased to 21.1% of patients taking the maximum daily dose 400 mg/day (during the 12-week maintenance phase).⁴ The most common adverse reactions reported included somnolence, dizziness, fatigue, vertigo, ataxia and headache.[7]

Professor Norman Delanty, Consultant Neurologist at Beaumont Hospital, Dublin said, “I am very pleased by the HSE’s decision to reimburse the use of cenobamate for eligible people who have epilepsies resistant to current anti-seizure medications. This marks a further important step forward in epilepsy care in Ireland, providing a much needed additional treatment option that has the potential to significantly reduce the frequency of focal-onset seizures.”

Peter Murphy, CEO at Epilepsy Ireland also commented on today’s announcement saying, “Epilepsy is one of the most common serious neurological conditions in Ireland, and while most people can become seizure-free, as many as 10,000-15,000 people are still living with uncontrolled seizures. For this group in particular, the condition can be a significant long-term, yet often hidden, disability. Living with epilepsy involves learning to cope not only with the physical impact of seizures, but with impaired psychological and social functioning, while stigma is still an issue reported by many. Along with loss of one’s driver’s license or employment, isolation and low self-esteem are all potential challenges that may cause as many problems as the seizures themselves.” He added, “Given the impact that refractory epilepsy can have on all aspects of a person’s life, it's extremely important that patients can access the best possible treatments. It is always encouraging to see the approval of effective new epilepsy medications and cenobamate will offer an additional treatment option for many people in Ireland who have so far struggled to achieve seizure freedom.”

Stuart Mulheron, Angelini, UK & Ireland General Manager commented, “We are committed to bringing life-changing treatments to people living with epilepsy and are delighted to be able to bring the benefits of cenobamate to the people of Ireland”.

Cenobamate is approved in the EU for the adjunctive treatment of focal-onset seizures with or without secondary generalisation in adult patients with epilepsy who have not been adequately controlled despite a history of treatment with at least two anti-epileptic medicinal products.⁷

-ENDS-

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Adverse events and product complaint should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard for the UK or www.hpra.ie for Ireland. Adverse events and product complaint should also be reported to Angelini Pharma on (UK) +44 2034889643, (IRE) +353 1 584 4671 or UKIReporting@angelinipharma.com

For more information, please contact:

Stuart Mulheron - UK & Ireland General Manager, Angelini Pharma - stuart.mulheron@angelinipharma.com

About Epilepsy

Epilepsy is a serious neurological condition that affects an estimated 40,000 people in Ireland.¹ Epilepsy is defined as the tendency to have repeated seizures which start in the brain.[8]

There are different types of seizures which are usually categorised into two groups: 1. generalised seizures which affect the whole brain or 2. focal seizures, also sometimes called partial seizures which affect one part of the brain. Depending on the function of the affected part of the brain, this will then determine the type of focal seizure. They can either be seizures with full awareness or limited awareness.⁸

About Cenobamate

Cenobamate was discovered and developed by SK Biopharmaceuticals and SK life science and is an FDA-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®.[9]

Cenobamate is a novel small molecule that provides a dual, complementary mechanism of action aimed at treatment of seizures.[10]^,[11] Cenobamate at clinically relevant concentrations, acts both as a positive allosteric modulator of GABA_A receptors at a non-benzodiazepine binding site and preferentially blocks the persistent sodium current.^11,[12] The dual mechanism of action of cenobamate suggests that it has the potential to both prevent seizure initiation and limit seizure spread. 10^,11,12,[13]

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.[14] 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 generalized tonic-clonic seizures (NCT03678753).[15]

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, Spain, Austria, Italy, France, Belgium, Switzerland, Luxembourg, Netherlands, Slovakia, Norway, Finland, Sweden, Denmark and UK under the trademark ONTOZRY®.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR CENOBAMATE

Cenobamate has received marketing authorisation in the EU and Great Britain 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 two anti-epileptic medicinal products. The recommended starting dose of cenobamate is 12.5 mg per day, titrated gradually to the recommended target dose of 200 mg per day. Based on clinical response, dose may be increased to a maximum of 400 mg per day.

Cenobamate is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients, and patients with familial Short-QT syndrome.

According to the cenobamate EU Risk Management Plan, the occurrence of drug rash with eosinophilia and systemic symptoms (DRESS) has been recognised as an important identified risk of the medicine. Important potential risks are hypersensitivity, suicidality (class effect), QT shortening and reproductive / embryofoetal toxicity.

In clinical trials, the most commonly reported adverse reactions were somnolence, dizziness, fatigue and headache. The approved Product Information of cenobamate includes the routine risk minimisation measures for reducing safety risks in patients treated with the medicinal product.

About C017

C017 was a multicentre, double-blind, randomised, 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. Following an 8-week baseline period, the study participants were randomised 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 percentage change from baseline in focal seizure frequency averaged over in 28 days in the 18-week double blind treatment period, and the responder rate (percentage of patients achieving ≥50% reduction from baseline in focal seizure frequency) during 12-week maintenance phase of the double-blind treatment period. Data from patients who had the option to be enrolled in an open-label extension of the C017 study will provide additional insight into the long-term clinical efficacy and safety profile of adjunctive cenobamate.

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 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 20 countries employing almost 3,000 people and commercialises its products in more than 70 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).

[1] Epilepsy Ireland. Epilepsy Facts and Myths. Available at: https://www.epilepsy.ie/content/epilepsy-facts-and-myths Accessed October 2022.

[2] Schmidt D et al. BMJ. 2014;348:g2546.

[3] National Institute for Health and Care Excellence. NICE Technical Appraisal Guidance [TA753]. Available at: https://www.nice.org.uk/guidance/ta753/chapter/3-Committee-discussion Accessed October 2022.

[4] Krauss L G et al. Lancet Neurol. 2020 Jan;19(1):38-48.

[5] Data on File.

[6] Epilepsy Ireland. Treatment. Available at: https://www.epilepsy.ie/content/treatment Accessed October 2022.

[7] Cenobamate Summary of Product Characteristics (SmPC). Available at: https://www.medicines.org.uk/emc/product/13012/smpc#gref Accessed October 2022.

[8] Epilepsy Society. Seizure Types. https://epilepsysociety.org.uk/about-epilepsy/epileptic-seizures/seizure-types Accessed October 2022.

[9] FDA. Cenobamate prescribing information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212839s000lbl.pdf Accessed October 2022.

[10] Guignet M et al. Epilepsia. 2020 Oct 16. doi: 10.1111/epi.16718.

[11] Sharma R et al. Eur J Pharmacol. 2020;879:173117.

[12] Nakamura M, et al. Eur J Pharmacol. 2019;855:175-182.

[13] Anderson LL et al. Epilepsia. 2014;55(8):1274-1283.

[14] Sperling MR, et al. Epilepsia. Feb 2020;61:1099–1108.

[15] Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures NCT03678753.