CLINICAL TRIALS PROFILE FOR CENOBAMATE

All Clinical Trials for Cenobamate

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01397968 ↗	Efficacy and Safety of YKP3089 in Subjects With Treatment Resistant Partial Onset Seizures	Unknown status	SK Life Science	Phase 2	2011-05-01	This study is to evaluate the efficacy of YKP3089 in reducing seizure frequency when compared to baseline in subjects with partial onset seizures not fully controlled despite their treatment with 1 to 3 concomitant anti-epileptic drugs. Also to evaluate the safety and tolerability of YKP3089.
NCT01397968 ↗	Efficacy and Safety of YKP3089 in Subjects With Treatment Resistant Partial Onset Seizures	Unknown status	SK Life Science, Inc.	Phase 2	2011-05-01	This study is to evaluate the efficacy of YKP3089 in reducing seizure frequency when compared to baseline in subjects with partial onset seizures not fully controlled despite their treatment with 1 to 3 concomitant anti-epileptic drugs. Also to evaluate the safety and tolerability of YKP3089.
NCT03234699 ↗	Assess the Influence of Cenobamate on the PK of Cytochrome P450 (CYP) Probe Drugs as a Means of Predicting Drug-drug Interactions	Completed	SK Life Science	Phase 1	2017-02-22	This study is aimed to investigate the influence of cenobamate on the activity of CYP3A4/5, CYP2B6, CYP2C19, and CYP2C9 by using drugs recommended by both the FDA and EMA as in vivo probes. In order to avoid a potential pharmacokinetic interaction between the probes, midazolam (CYP3A), warfarin (CYP2C9), and omeprazole (CYP2C19) will be administered together as a validated cocktail and separately from bupropion (CYP2B6) using an adequate washout time period between the 2 assessments. The starting daily dose of cenobamate will be 12.5 mg, which will be administered for 2 weeks. Then, daily cenobamate doses will be increased every 2 weeks to 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg. The CYP probes will be tested before cenobamate administration, at steady state at 100mg/day of cenobamate for midazolam only and finally at steady state at 200mg/day of cenobamate for all CYP probes. The results of this DDI study will provide a basis to make appropriate dose recommendation for a safe use of concomitant drugs with cenobamate using these isoenzymes in their metabolic pathway.
NCT03234699 ↗	Assess the Influence of Cenobamate on the PK of Cytochrome P450 (CYP) Probe Drugs as a Means of Predicting Drug-drug Interactions	Completed	SK Life Science, Inc.	Phase 1	2017-02-22	This study is aimed to investigate the influence of cenobamate on the activity of CYP3A4/5, CYP2B6, CYP2C19, and CYP2C9 by using drugs recommended by both the FDA and EMA as in vivo probes. In order to avoid a potential pharmacokinetic interaction between the probes, midazolam (CYP3A), warfarin (CYP2C9), and omeprazole (CYP2C19) will be administered together as a validated cocktail and separately from bupropion (CYP2B6) using an adequate washout time period between the 2 assessments. The starting daily dose of cenobamate will be 12.5 mg, which will be administered for 2 weeks. Then, daily cenobamate doses will be increased every 2 weeks to 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg. The CYP probes will be tested before cenobamate administration, at steady state at 100mg/day of cenobamate for midazolam only and finally at steady state at 200mg/day of cenobamate for all CYP probes. The results of this DDI study will provide a basis to make appropriate dose recommendation for a safe use of concomitant drugs with cenobamate using these isoenzymes in their metabolic pathway.
NCT03509285 ↗	A Study of the Abuse Liability Potential of Cenobamate in Recreational Drug Users	Completed	SK Life Science	Phase 1	2017-03-08	This randomized, single-dose, placebo- and active-controlled, crossover study will evaluate the abuse liability potential of cenobamate in recreational drug users with sedative drug use experience. In the Qualification phase, subjects will receive a single dose of either alprazolam or placebo in a crossover design, with a wash-out period of at least 24 hours between treatments. Subjects who are clearly able to distinguish the positive control from placebo will be enrolled in the Treatment phase and will be randomized to single oral doses of cenobamate (2 dose levels), alprazolam (2 dose levels), and placebo in a double-blind, double-dummy, 5-way crossover design. Washout-periods between the 5 treatment periods in the Treatment phase will be at least 16 days.

Clinical Trial Conditions for Cenobamate

Condition Name

Condition Name for Cenobamate
Intervention	Trials
Partial Epilepsy	3
Healthy	2
Primary Generalized Tonic Clonic Seizures in the Setting of Idiopathic Generalized Epilepsy	1
Focal Seizure	1

Condition MeSH

Condition MeSH for Cenobamate
Intervention	Trials
Seizures	6
Epilepsies, Partial	3
Epilepsy	3
Epilepsy, Generalized	2

Clinical Trial Locations for Cenobamate

Trials by Country

Trials by Country for Cenobamate
Location	Trials
United States	41
Poland	14
Ukraine	10
India	5
Bulgaria	3

Trials by US State

Trials by US State for Cenobamate
Location	Trials
Maryland	5
Pennsylvania	3
Florida	3
California	3
Washington	2

Clinical Trial Progress for Cenobamate

Clinical Trial Phase

Clinical Trial Phase for Cenobamate
Clinical Trial Phase	Trials
Phase 3	4
Phase 2	1
Phase 1	6

Clinical Trial Status

Clinical Trial Status for Cenobamate
Clinical Trial Phase	Trials
Recruiting	4
Completed	3
Not yet recruiting	1

Clinical Trial Sponsors for Cenobamate

Sponsor Name

Sponsor Name for Cenobamate
Sponsor	Trials
SK Life Science, Inc.	11
SK Life Science	3

Sponsor Type

Sponsor Type for Cenobamate
Sponsor	Trials
Industry	14

Cenobamate: Clinical Trials Update, Market Analysis, and Projections

Introduction

Cenobamate, marketed under the brand name XCOPRI, is a novel anti-seizure medication (ASM) developed by SK Biopharmaceuticals and SK Life Science, Inc. It has been approved for the treatment of partial-onset seizures in adults and has shown promising results in various clinical trials and real-world studies. Here, we will delve into the latest updates on clinical trials, market analysis, and future projections for cenobamate.

Clinical Trials Update

Phase 3 Open-Label Extension Study

A significant ongoing study is the 52-week open-label extension study (NCT03961568) designed to evaluate the long-term safety of cenobamate as an adjunctive therapy in subjects who complete the double-blind study YKP3089C025. This study includes a 12-week double-blind conversion phase where patients who received placebo are titrated to cenobamate, and those already on cenobamate continue their treatment. The titration process involves gradual dose increases to 200 mg over 12 weeks. Following this phase, patients enter a 40-week open-label, flexibly dosed period with cenobamate, with doses ranging from 50 mg to 200 mg[1].

Efficacy and Safety Data

Post-hoc analyses from Phase 2 and 3 trials have shown that cenobamate leads to significant reductions in seizure frequency. For instance, data from 214 patients in an open-label Phase 3 study indicated that 87.9% and 67.8% of patients achieved ≥50% and 100% seizure reduction, respectively, over any 3-month interval. Additionally, patients experienced a reduction in their average drug load by 29% and 32% after 12 and 24 months of treatment with cenobamate[3].

Real-World Experience

Recent updates on real-world experience with cenobamate, published in Epilepsia, highlight its effectiveness in over 100,000 unique patient exposures across various markets. This data supports the clinical trial findings, showing that cenobamate reduces repetitive neuronal firing by inhibiting voltage-gated sodium currents and acting as a positive allosteric modulator of the GABA_A ion channel[2].

Market Analysis

Approval and Availability

Cenobamate is approved in the United States for the treatment of partial-onset seizures in adults and is also approved in the European Union, Switzerland, the UK, Israel, and Canada. It is marketed by Dexcel and Paladin under the brand name XCOPRI[2].

Market Share and Adoption

The drug has seen increased adoption among epileptologists, general neurologists, and advanced practice providers. The milestone of 100,000 patient exposures indicates a growing market share, which is expected to continue as more healthcare providers become familiar with its efficacy and safety profile[2].

Financial Impact

A budget impact analysis conducted in the Netherlands suggests that the adoption of cenobamate can lead to significant cost savings. The study projects that an increase in cenobamate's market share could result in savings of €31,920,955 over five years, primarily due to reduced productivity and seizure event management costs[5].

Projections and Future Outlook

Continued Growth

Given its strong clinical trial data and real-world efficacy, cenobamate is projected to continue growing in the market. The drug's ability to reduce the average drug load for patients while maintaining or improving seizure control is a significant advantage, likely to attract more prescribers and patients[3].

Expanding Indications

While currently approved for partial-onset seizures, ongoing and future studies may explore the potential of cenobamate for other types of seizures and epilepsy conditions. This could further expand its market reach and solidify its position as a leading anti-seizure medication[4].

Competitive Landscape

Cenobamate competes with other anti-seizure medications such as perampanel, brivaracetam, and lacosamide. However, its unique mechanism of action and favorable safety and efficacy profile position it well in the market. As more data becomes available, cenobamate is likely to gain a stronger foothold against its competitors[5].

Key Takeaways

• Clinical Efficacy: Cenobamate has demonstrated significant reductions in seizure frequency and a favorable safety profile in both clinical trials and real-world studies.
• Market Adoption: The drug has seen substantial adoption, reaching a milestone of 100,000 patient exposures, and is expected to continue growing.
• Financial Impact: Adoption of cenobamate can lead to significant cost savings due to reduced productivity and seizure event management costs.
• Future Outlook: Cenobamate is projected to continue growing, with potential for expanding indications and a strong competitive position.

FAQs

What is cenobamate used for?

Cenobamate is used for the treatment of partial-onset seizures in adults. It is marketed under the brand name XCOPRI.

How does cenobamate work?

Cenobamate works by inhibiting voltage-gated sodium currents and acting as a positive allosteric modulator of the GABA_A ion channel, reducing repetitive neuronal firing.

What are the common side effects of cenobamate?

Common treatment-emergent adverse events include fatigue, dizziness, and somnolence[4].

Is cenobamate approved in multiple regions?

Yes, cenobamate is approved in the United States, the European Union, Switzerland, the UK, Israel, and Canada[2].

What are the financial implications of adopting cenobamate?

Adopting cenobamate can lead to significant cost savings, primarily due to reduced productivity and seizure event management costs[5].

Sources

1. ClinicalTrials.gov: Cenobamate Open-Label Extension Study for YKP3089C025.
2. PR Newswire: SK Life Science Publishes Updated Real-World Experience on Cenobamate in Epilepsia.
3. PR Newswire: Latest XCOPRI® (cenobamate tablets) CV Post-hoc Analysis Presented at the 75th American Academy of Neurology Annual Meeting.
4. Wiley Online Library: Efficacy of cenobamate for uncontrolled focal seizures: Post hoc analysis of a Phase 3, multicenter, open-label study.
5. ISPOR: Budget Impact Analysis of Cenobamate for Epilepsy Patients with Focal Onset Seizures.