In which countries is Cenobamate approved?

Introduction to Cenobamate

Overview and Mechanism of Action
Cenobamate is a novel oral small‐molecule neurotherapeutic agent discovered and developed by SK Biopharmaceuticals and SK Life Science, Inc. It is recognized as a breakthrough anti‐seizure medication (ASM) with a dual, complementary mechanism of action. On a molecular level, cenobamate enhances the inactivated state of voltage-gated sodium channels through preferential blockade of the persistent sodium current, thereby reducing repetitive neuronal firing. Simultaneously, it acts as a positive allosteric modulator of the γ-aminobutyric acid (GABAA) ion channel at a non-benzodiazepine binding site. This duality contributes significantly to its robust anticonvulsant effects and distinguishes it from many other ASMs, offering promising efficacy in patients with refractory focal-onset seizures. Its mechanism was initially explored through preclinical screening using well-established animal models, and subsequent studies confirmed its beneficial actions without causing significant neurotoxicity or cell death.

Therapeutic Uses
Cenobamate is primarily indicated for the treatment of partial-onset seizures in adult patients with epilepsy who have not achieved adequate seizure control with at least two other anti-seizure medications. Its therapeutic utility extends to addressing drug-resistant epilepsy, a condition that affects roughly one-third of patients even with multiple ASMs available. Clinically, cenobamate has shown significant effects in reducing seizure frequency and even achieving seizure freedom in a subset of patients. The drug’s unique pharmacological profile suggests that beyond seizure reduction, it might contribute to improved quality of life for patients by minimizing adverse effects that typically accompany conventional therapies. Moreover, its availability as a once-daily tablet further optimizes patient compliance and convenience, emphasizing its role in modern epilepsy management.

Regulatory Approval Process

General Drug Approval Process
The process of bringing a new drug to market is complex and rigorous, involving a series of preclinical and clinical evaluations to establish safety, efficacy, pharmacokinetics, and pharmacodynamics. Typically, drug approval requires extensive documentation that includes phase 1 through phase 3 clinical trials, supporting animal studies, manufacturing process validations, and quality assurance assessments. Regulatory agencies such as the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), and Health Canada conduct detailed reviews of submitted data through processes that might include accelerated pathways, conditional approvals, or expedited reviews for drugs that address serious medical conditions or unmet needs.
Furthermore, the drug approval process is characterized by multiple stages—from the initial Investigational New Drug (IND) application to New Drug Application (NDA) or Marketing Authorization Application (MAA) submission—and typically involves external advisory committees, risk–benefit assessments, and extensive post-approval monitoring to ensure ongoing safety. Such comprehensive evaluations ensure that only those drugs with a favorable therapeutic index are granted approval, providing assurance to both clinicians and patients.

Specifics for Cenobamate
For cenobamate, the regulatory evaluation followed this rigorous pathway. The clinical development program showcased robust data through two pivotal phase 2 trials and a phase 3 trial where significant reductions in seizure frequency were observed compared to placebo. The impressive efficacy data, including seizure freedom rates approaching almost one-fifth to almost one-fourth of patients in some studies, played a crucial role in its regulatory success.
The termination of early concerns—such as drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)—once a slower titration schedule was instituted further supported its safety profile. Such modifications to the dosage regimen were based on early trial observations, which then paved the way for an open-label long-term safety study confirming the tolerability of the adjusted titration approach. Ultimately, the positive benefit–risk profile facilitated accelerated regulatory reviews, culminating in approval decisions that not only underscored its innovative mechanism of action but also the need for newer therapeutic options in refractory focal epilepsy.

Countries with Approval

Major Markets
The major markets where cenobamate has been approved are characterized by well-established regulatory structures and a high incidence of epilepsy, ensuring both scientific scrutiny and market readiness.

• United States of America – Cenobamate was approved by the FDA in November 2019 and is commercially available under the trade name XCOPRI® for the treatment of partial-onset seizures in adult patients. This approval has been widely celebrated because the United States maintains one of the most rigorous regulatory standards, which implies that cenobamate has met high benchmarks for efficacy and safety. The extensive clinical data and support from multiple randomized clinical trials contributed to the confidence of regulators and the epilepsy community alike.

• European Union – Following a positive advisory opinion from the Committee for Medicinal Products for Human Use (CHMP) in January 2021, cenobamate has been approved by the European Medicines Agency (EMA) for adjunctive treatment of focal-onset seizures. In the EU, it is marketed under the trade name ONTOZRY®. The approval covers a broad range of European countries including, but not limited to, key markets such as Germany, France, Italy, Spain, and the United Kingdom. Additionally, the approval implicitly extends to countries that are not EU members but adhere to EMA standards, like Switzerland.
 
• Canada – Cenobamate has also received approval in Canada, where Paladin Labs Inc. launched the product in January 2024. The Canadian market’s adherence to robust review processes similar to those of the FDA and EMA strengthens the trust in this newly approved therapeutic agent.

• Israel – In Israel, Dexcel Pharma has been granted rights to develop and commercialize cenobamate for the treatment of partial-onset seizures. The product was set to launch in April 2024, marking another significant milestone for the drug in addressing drug-resistant epilepsy in the region.

These major markets serve as proof of the international recognition that cenobamate has received based on its compelling clinical profile and thorough regulatory validation.

Emerging Markets
Besides these established markets, cenobamate is actively being developed or licensed for commercialization in several emerging regions. While formal approval status might still be under review in some of these territories, the strategic licensing agreements indicate strong prospects for future approval based on existing clinical data and regulatory endorsements from major markets.

• Greater China Region – Under the partnership with Ignis Therapeutics (Suzhou) Limited, cenobamate is being developed for the Greater China area, which includes mainland China, Hong Kong, Macau, and Taiwan. This licensing agreement demonstrates the intention to eventually navigate the regulatory landscape in these jurisdictions, which have been increasingly focusing on innovative ASMs.

• Japan – Ono Pharmaceutical Co., Ltd. has obtained rights to develop and commercialize cenobamate in Japan. Given Japan’s stringent but well-defined regulatory framework for new drug approvals, this move indicates that clinical data from the U.S. and Europe may soon facilitate local approval, expanding the accessibility of cenobamate in an important Asian market.

• Latin America – A licensing agreement between SK Bio-Pharmaceutics and Eurofarma for cenobamate in Latin America signifies that the drug is on its way to becoming available in over 20 markets across the region. Although final approvals may be pending in certain countries, the commercial arrangement indicates confidence in its performance and the fulfillment of regulatory requirements within Latin America.

• Middle East and North Africa (MENA) – Hikma Pharmaceuticals and SK Biopharmaceuticals have entered into strategic partnerships to bring cenobamate to the MENA region. Although this initiative is in its earlier stages compared to the U.S. and EU approvals, it reflects the growing recognition of the drug’s clinical value, especially in regions with a high prevalence of epilepsy.

In summary, while cenobamate is currently approved in major markets such as the USA, the European Union (including the United Kingdom and Switzerland), Canada, and Israel, licensing and development activities in regions like Greater China, Japan, Latin America, and the MENA region signal a robust pipeline towards eventual approval and commercialization in these emerging markets.

Implications of Approval

Market Impact
The approval of cenobamate in key regulatory jurisdictions carries significant market implications. In the United States, the availability of XCOPRI® presents a new option for patients who have struggled with drug-resistant focal-onset seizures. The impressive clinical results, which include both significant reductions in seizure frequency and relatively high seizure-freedom rates, are likely to influence treatment protocols and prompt re-evaluation of existing ASM regimens. Meanwhile, within the European Union, the approval of ONTOZRY® not only brings a novel treatment to a diverse patient population but also strengthens the market competitiveness of European pharmaceutical firms by diversifying the therapeutic portfolio for epilepsy treatment.
Furthermore, the approvals in Canada and Israel enhance the global narrative of cenobamate as a forward-looking treatment with broad applicability. They serve as case studies of regulatory convergence where rigorous scientific assessment leads to international consensus on therapeutic value. The multinational approvals support a market expansion strategy that leverages existing clinical data to overcome regional regulatory challenges, thereby helping to streamline pricing and reimbursement policies on a global scale. Lastly, the strategic licensing deals in emerging markets indicate that cenobamate is positioned to gradually penetrate additional territories, further cementing its role in the global epilepsy treatment market.

Patient Access and Benefits
For patients worldwide, the approval of cenobamate represents the promise of better seizure management and an enhanced quality of life. With nearly one-third of epilepsy patients remaining drug-resistant despite numerous available medications, the introduction of an agent like cenobamate increases treatment options considerably.
Patients in the United States now have access to a medication that has been shown to provide an independent pathway for seizure control through its dual mechanism of action. This is particularly important as traditional ASMs often share common side effects and limited options for seizure freedom. Similarly, in the European Union, the availability of ONTOZRY® broadens the spectrum of treatment options for physicians, allowing a more tailored approach to managing drug-resistant epilepsy. The streamlined dosing schedule—once-daily administration—facilitates medication adherence, minimizing the challenges posed by polytherapy regimens that many refractory patients face.
In emerging markets where cenobamate is under development or awaiting approval, collaborations with local partners are geared towards optimizing patient access. For instance, the licensing agreements in Latin America, Greater China, and Japan are designed not only to meet regulatory requirements but also to adapt the marketing and distribution strategies to the specific healthcare landscapes in those regions. As a result, patients in these emerging markets are anticipated to benefit from early access programs or even post-marketing surveillance initiatives that ensure longstanding safety and efficacy. Leaders in epilepsy care across these regions are preparing for cenobamate’s arrival by retraining clinicians in its proper dosing and titration, thereby mitigating risks such as DRESS syndrome through cautious and informed treatment practices.

In addition, the anticipated global spread of cenobamate through established regulatory channels signifies a major step forward in addressing an otherwise unmet medical need. By expanding the geographic footprint of its availability, cenobamate is set to reduce the burden of uncontrolled seizures worldwide, offering hope especially to patients who have exhausted other medical options. The broader therapeutic landscape not only enhances individual patient outcomes but also reduces the overall economic and social costs of epilepsy, which include frequent emergency room visits, hospitalizations, and long-term morbidity.

Conclusion
Cenobamate’s approval across several major regulatory markets highlights its significant therapeutic potential and its robust clinical profile. Based on the above references, the drug is approved in the United States—where it is marketed as XCOPRI®—and in the European Union, with countries such as Germany, France, Italy, Spain, the United Kingdom, and Switzerland having access to ONTOZRY®. Additionally, it is now approved in Canada and Israel. These approvals came on the back of extensive clinical trials demonstrating high efficacy in reducing seizure frequency and achieving seizure freedom in patients with refractory focal-onset seizures.

From a broader perspective, significant licensing and development activities have been initiated for emerging markets, including the Greater China region, Japan, Latin America, and the MENA region. Although formal regulatory approval in these areas may be pending, the established partnerships indicate strong confidence in cenobamate’s clinical benefits and its anticipated global reach.

The implications of these regulatory milestones are profound. They not only introduce a vital new treatment option for patients suffering from drug-resistant epilepsy but also reshape the competitive landscape in the ASM market. In major markets, robust regulatory decisions validate the drug’s efficacy and safety, while emerging markets are poised to benefit from localized development initiatives that promise to enhance access and affordability. Ultimately, the global expansion of cenobamate underscores the importance of innovative therapies in addressing the unmet clinical needs of individuals with refractory epilepsy, thereby potentially transforming patient outcomes and elevating standards of care across diverse healthcare systems.

In conclusion, cenobamate is approved in the United States, the European Union (including the United Kingdom and Switzerland), Canada, and Israel. It represents a significant advancement in the management of partial-onset seizures, with strong evidence supporting its use and a clear trajectory toward further market expansion. The multilayered review process, guided by stringent regulatory frameworks and bolstered by extensive clinical data, ensures that patients receive a treatment option that is not only innovative but also safe and effective. As licensing and development efforts continue in emerging regions, the promise of improved seizure control and enhanced quality of life for epilepsy patients worldwide becomes increasingly attainable.