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ONTOZRY™ (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, Jan. 29, 2021 (GLOBE NEWSWIRE) -- 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 epilepsy1 and approximately 40% of adult people with epilepsy have inadequate control of seizures after treatment with two anti-seizure medications (ASMs).2

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 Neurology3 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.4,5 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.4,6

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.7,8

*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.

About Arvelle Therapeutics
Arvelle Therapeutics is an emerging biopharmaceutical company focused on bringing innovative solutions to patients suffering from CNS disorders. Arvelle is responsible for the development and commercialization of cenobamate, an investigational anti-seizure medicine, in the European market. Arvelle is headquartered in Switzerland and received start-up financing of $207.8 million, one of the largest initial financing commitments for a European-focused biopharmaceutical company, with investments from a global syndicate including NovaQuest Capital Management, BRV Capital Management, LSP, H.I.G. BioHealth Partners, Andera Partners, F-Prime Capital and KB Investments. More information is available at https://arvelletx.com.

About Angelini Pharma
Angelini Pharma is an international pharmaceutical company, part of the Italian privately-owned Angelini Group. Angelini Pharma is committed to helping patients in the therapeutic areas of Mental Health (including Pain), Rare Diseases and Consumer Healthcare. 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 commercializes 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 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).

About SK Biopharmaceuticals Co., Ltd.
SK Biopharmaceuticals and its U.S. subsidiary SK life science are global pharmaceutical companies focused on the research, development and commercialization of treatments for disorders of the central nervous system (CNS). The companies have a pipeline of eight compounds in development for the treatment of CNS disorders, including epilepsy. Additionally, SK Biopharmaceuticals is focused on early research in oncology. For more information, visit SK Biopharmaceuticals’ website at www.skbp.com/eng and SK life science’s website at www.SKLifeScienceInc.com.

About Cenobamate
Cenobamate was discovered 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 has been approved in the U.S. where it is commercially available under the trademark XCOPRI®.9  IMPORTANT SAFETY INFORMATION AND INDICATION FOR XCOPRI® (cenobamate tablets) CV can be found on www.xcopri.com

Cenobamate is a novel small molecule that provides a unique, dual, complementary mechanism of action aimed at treatment of seizures.10,11,12 Cenobamate is the only anti-seizure medication which, 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.11,12 The unique dual mechanism of action of cenobamate suggests that it has the potential to both prevent seizure initiation and limit seizure spread.13,14,15,16,17

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.18 Additionally, cenobamate is being assessed in an ongoing randomized, double-blind, placebo-controlled trial evaluating its safety and efficacy as adjunctive therapy in patients with primary generalized tonic-clonic seizures (NCT03678753).19

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 UK Medicines and Healthcare Products Regulatory Agency (MHRA) has designated cenobamate as a Promising Innovative Medicine (PIM). A PIM designation is an early indication that a medicinal product is a promising candidate for the Early Access to Medicines Scheme.

In addition, as of August 2020, the German Federal Institute for Drugs and Medical Devices (BfArM) has included cenobamate for the treatment of drug-resistant focal-onset seizures in adults in its list of confirmed drugs for compassionate use (CPU) programmes for one year within the country.

About Study 0173
Study 017 was 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 had the option to enrol in an open-label extension of the 017 study will provide additional insight into the long-term clinical efficacy and safety profile of adjunctive cenobamate.

References

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. 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. Seizure. 2002;11:356–360.
7. Engel J. Neurol. 2003;60(9):1412.
8. Engel J. Ann Indian Acad Neurol. 2014;17(Suppl 1):S12–7.
9. Cenobamate prescribing information. FDA. Last accessed 20 July, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212839s000lbl.pdf 
10. Guignet M, Campbell A, White HS, Epilepsia. 2020 Oct 16. doi: 10.1111/epi.16718. Online ahead of print
11. Nakamura M, et al. Eur J Pharmacol 2019;855:175-182.
12. Sharma R, et al. Eur J Pharmacol 2020;879:173117.
13. Anderson LL et al., Epilepsia 2014; 55(8):1274-1283.
14. Piredda SG et al, J Pharmacol Exp Ther. 1985;232(3):741-745.
15. Stafstrom CE, Epilepsy Curr 2007; 7(1):15-22.
16. Vreugdenhil M et al., Eur J Neurosci., 2004; 19: 2769-2778.
17. White HS et al, Epilepsy Res. 1997;28(3):167-79.
18. Sperling MR, et al. Epilepsia, Feb 2020;61:1099–1108.
19. Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures NCT03678753.


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