Angelini Pharma Presents Long-Term Data for cenobamate (ONTOZRY®) Demonstrating Sustained Benefit in Adults with Epilepsy Experiencing Uncontrolled Focal Seizures

• Findings from a post-hoc analysis of the C017 open-label extension study demonstrated 23.6% of patients receiving adjuvant treatment with cenobamate achieved sustained seizure freedom for at least one year
• Additional post-hoc analyses found that patients who did not achieve complete seizure freedom but were able to maintain a 90–99% reduction in seizure frequency for up to five years were seizure-free approximately 98% of study days
• Compelling clinical response combined with the well-tolerated safety profile continue to support use of cenobamate in the treatment of adults with epilepsy experiencing uncontrolled focal seizures

Rome (Italy) 4 Sep 2023 – Angelini Pharma, part of the privately owned Angelini Industries, today shared positive findings from post-hoc analyses of the C017 open-label extension (OLE) study, which demonstrated that adjunctive treatment with cenobamate provided long-term seizure reduction, including seizure freedom, among certain patients with uncontrolled focal-onset epilepsy. Results are being presented as part of the 35th International Epilepsy Congress 2023 in Dublin (Ireland).

Cenobamate is an anti-seizure medication (ASM) approved in Europe 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 two anti-epileptic medicinal products.

In a post-hoc analysis of the C017 open-label extension (OLE) study (abstract #1324), seizure freedom for at least one year was achieved by 23.6% of the patients with 19% achieving seizure freedom from the first day of treatment in the OLE. The results also show14.3% of patients achieved seizure freedom for at least two years and 7.5% of patients for at least three years. More than half (58.1%) of patients had no focal to bilateral tonic clonic (FBTC) seizures for at least one year, 42.6% for at least two years and 27.8% for at least three years with 25%, 21.9% and 17.2% of the patients achieving seizure freedom from day one of treatment in the OLE, respectively.

Findings also showed that cenobamate reduced the day-to-day seizure burden in patients with inadequately controlled focal seizures by significantly increasing the number of days with fewer or no seizures in those patients who did not achieve long-term seizure freedom. An additional post-hoc analysis from the C017 OLE study (abstract #151) showed that 17% of patients who achieved a 90-99% reduction in seizure frequency maintained this response during the length of their participation in the study (median = 291.3 weeks/5.5 years), with approximately 98% of days seizure-free and a 93.7% reduction in risk of days with seizures.

Most (92%) of the patients treated with cenobamate who achieved a 90-99% reduction in seizure frequency were seizure-free at least 95% of the days throughout the study duration; 43.2% were seizure-free 99% of the days throughout the study duration.  Results also showed that the number of days with seizures decreased along the years, ranging between 3.6% (year 1) and 1.2% (year 5). These outcomes, together with the favorable tolerability and safety profile, led to retention rates of 90% after five years, considerably higher than those of the entire population, 60% after five years.

Further post-hoc analysis of the OLE study (abstract #1071) evaluated the seizure-free days for patients based on responder rates (≥50%, ≥75%, and ≥90%), concomitant ASMs and number of previously failed ASMs, showing ≥50% responders remained seizure-free for 91.8% of the days, ≥75% responders remained 96.3% of the days seizure-free, and ≥90% responders stayed 98.2% of the days seizure-free. The observed improvements were independent of the mechanism of action of the concomitant ASMs. When looking at the percentage of seizure-free days in patients who had failed a different number of ASMs, the rate ranged from 81.7% for those failing at least seven ASMs to 91.0% for those who only failed one to two ASMs.

“The objective of epilepsy treatment is to achieve and maintain seizure freedom, but this is not always possible for many patients despite active treatment with anti-seizure medications,” said Dr. Manuel Toledo, Hospital Vall d’Hebron and Associate Professor, Universidad Autonoma de Barcelona, Spain. “Findings from a post-hoc analysis of the C017 open-label extension study showed adjunctive treatment with cenobamate helped 17% of patients achieve a 90-99% reduction in seizure frequency, with approximately 98% of seizure-free days and responses maintained for up to five years. These data demonstrate high levels of sustained seizure reduction are possible and help inform clinical practice so we can help more patients with uncontrolled seizures live more of their days with fewer seizures.”

“People living with uncontrolled focal seizures are often overlooked in the healthcare system as they typically receive active – yet suboptimal – treatment,” said Agnese Cattaneo, Chief Medical Officer, Angelini Pharma. “We are committed to bringing these treatment gaps to light and helping as many people living with epilepsy and uncontrolled focal seizures as possible as these impact every aspect of day-to-day life and are associated with severe comorbidities such as the inability to carry out day-to-day activities, injury, and even premature death. We are pleased to see these positive post-hoc analyses of the C017 open-label extension study as they reaffirm that adding cenobamate could help provide higher, long-term seizure control for these patients.”

Summary of Baseline Demographics and Safety Findings

Baseline Demographics and Disease Characteristics of CO17 OLE Trial Patients*

*Baseline demographics similar across reported post-hoc analyses

Tolerability and Safety Profile

The subpopulations analyzed in the three post-hoc analyses of the open-label extension (OLE) study were evaluated against the total baseline modified intention to treat (mITT) patient population defined as all patients who had taken at least one dose of cenobamate and had any seizure data recorded in the OLE. The baseline demographics and safety profile of all populations studied were consistent with prior data and similar to the entire mITT population. No new safety concerns were found.

About Epilepsy

Epilepsy is one of the most widespread neurological diseases in the world, affecting approximately 50 million people of all ages.¹ In Europe, approximately six million people are estimated to be living with this disease.² Epilepsy can have multiple potential causes, including genetics and other factors, though approximately half of cases worldwide do not have a known cause.¹

The complications associated with epilepsy are severe, with a risk of premature mortality up to two times higher than the general population.¹ The recurrent seizures associated with this condition also have wide-ranging effects on a person’s broader physical and mental health, education and employment opportunities and other quality of life factors such as social relationships.¹

Treatments are available to help reduce seizures and improve quality of life, and approximately 70% of people living with epilepsy are thought to be responsive to these treatments.¹

About the C017 Open-Label Extension Study

C017 was a multicenter, double-blind, randomized, placebo-controlled, dose-response study to evaluate the safety and efficacy of cenobamate as an adjunctive therapy in adults with uncontrolled focal epilepsy despite treatment with one to three anti-seizure medications (ASMs). Patients who completed the double-blind study and met study eligibility had the option to enroll in an open-label extension (OLE) to provide additional insight into the long-term clinical and safety profile of adjunctive cenobamate.

Of the total modified intention to treat (mITT) participants (n=354) within the OLE study, 75% (n=265) were randomized to cenobamate and 25% (n=90) to placebo. All patients underwent a two-week double-blind conversion to a target dose of cenobamate 300 mg. During the OLE treatment phase, concomitant ASMs could be added, removed, or adjusted and the product dose could be adjusted.

About cenobamate (ONTOZRY^®)

Cenobamate is an anti-seizure medication (ASM) approved in Europe as adjunctive treatment of focal-onset seizures with or without secondary generalization in adult patients living with epilepsy who have not been adequately controlled despite a history of treatment with at least two anti-epileptic medicinal products.

Cenobamate is a novel small molecule that provides a unique, dual, complementary mechanism of action aimed at treatment of seizures. The unique dual mechanism of action suggests that it has the potential to both prevent seizure initiation and limit seizure spread.^3,4

Cenobamate was discovered and developed by SK Biopharmaceuticals and and its U.S. subsidiary SK Life Science.

Long-term data on cenobamate is being studied in open-label extensions of the double-blind placebo-controlled trials, as well as the open-label safety studies in adults with uncontrolled focal-onset seizures. Additionally, the product 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).^5–9

References

1. WHO. “Epilepsy Key Facts.” N.p., 9 Feb. 2023. Web. 24 Aug. 2023.

2. Zarocostas J. BMJ 2010; 341 :c4756 doi:10.1136/bmj.c4756

3. Guignet et al. Epilepsia 2020;61:2329–39

4. Löscher et al. Epilepsia 2021;62:596–614

5. French et al. Epilepsia 2021;62:2142–50

6. Klein et al. Neurology 2022, 99 (10) e989–e998

7. Chung et al. Neurology 2020;94:e2311–e22

8. Krauss et al. Lancet Neurol 2020;19:38–48

9. Sperling et al. Epilepsia 2020;61:1099–108