The US Food and Drug Administration (FDA) has approved Sunovion Pharmaceuticals Inc's (Sunovion) supplemental New Drug Application (sNDA) for the use of Aptiom (eslicarbazepine acetate) as monotherapy for the treatment of partial-onset seizures.
This new approved indication allows Aptiom to be used as monotherapy in people who initiate treatment for the first time or convert from other antiepileptic drugs (AEDs) to Aptiom. Previously approved in 2013 by the FDA as adjunctive therapy for partial-onset seizures, Aptiom is the only exclusively once-daily non-extended release AED, which can be used alone or in combination with other AEDs in the treatment of partial-onset seizures.
“We are pleased to have achieved FDA approval of a monotherapy indication for Aptiom, based on the results of two identically designed phase 3 clinical studies conducted by Sunovion. Data from the monotherapy trials, in addition to the data generated from the adjunctive trials, confirm that Aptiom is efficacious and well-tolerated as adjunctive or monotherapy treatment within a daily dose range of 800 to 1,600 milligrams. Prescribers now have greater flexibility to optimise clinical response and tolerability when using Aptiom to treat people with partial-onset seizures,” said Antony Loebel, M.D., executive vice president and chief medical officer, Sunovion Pharmaceuticals Inc., and head of global clinical development for Sumitomo Dainippon Pharma Group.
The approval of Aptiom as monotherapy for partial-onset seizures was supported by data from two pivotal phase 3 clinical trials (Studies 093-045 and 093-046). Both trials met the pre-specified primary endpoint agreed upon with the FDA.
“Sunovion has an ongoing commitment to people living with epilepsy. This approval reinforces our track record of bringing CNS therapies to market,” said David Frawley, senior vice president and chief commercial officer, Sunovion.
“We believe that Aptiom provides an additional therapeutic option to a larger group of people with partial-onset seizures, since Aptiom can now be used both as a monotherapy, as well as an adjunctive treatment.”
“Epilepsy is a common medical condition. About a third of the approximately three million people in the US who have epilepsy do not have fully successful treatment with current approaches,” said John Stern, M.D., director, epilepsy clinical programme and professor, UCLA department of neurology.
“The approval of Aptiom as a monotherapy for partial-onset seizures is based on clinical studies that provide valuable information regarding the treatment of people with epilepsy."
Two identically designed phase 3, dose-blinded, historical-controlled, multi-center, randomized clinical trials (Studies 093-045 and 093-046) evaluated the safety and efficacy of Aptiom (1,600 mg/day or 1,200 mg/day) as monotherapy for partial-onset seizures in patients 16 years of age or older whose seizures were not well-controlled with other antiepileptic drugs (AEDs).
The primary endpoint for both trials was the percentage of patients who exited the study due to pre-defined criteria identifying worsening seizure control, compared to historical controls from previous, similarly designed trials of epilepsy patients converting to AED monotherapy. Trial results showed that conversion to Aptiom monotherapy was associated with exit rates superior to historical controls in patients with partial-onset seizures, who were not well-controlled by one or two current AEDs.
Aptiom administered once-daily was generally well tolerated in both dose strengths. In the Aptiom monotherapy trials, the most common treatment-related adverse events, headache, dizziness, fatigue, somnolence, and nausea, were mainly mild or moderate in severity.
Aptiom is the latest member of the dibenzazepine carboxamide family of antiepileptic drugs (AEDs), an established class of medicines. Aptiom is the only exclusively once-daily, non-extended release AED now FDA-approved for use as monotherapy or adjunctive therapy for partial-onset seizures. The precise mechanism(s) by which eslicarbazepine, the primary active metabolite of Aptiom, exerts anticonvulsant activity is unknown but is thought to involve inhibition of voltage-gated sodium channels. Aptiom can be taken whole or crushed, with or without food. Aptiom is not classified as a controlled substance by the FDA.
The initial research and development of eslicarbazepine acetate was performed by BIAL-Portela & Ca, S.A. (BIAL), a privately held Portuguese research-based pharmaceutical company. Subsequently, Sunovion acquired the rights under an exclusive license to further develop and commercialise eslicarbazepine acetate in the United States and Canadian markets from BIAL. BIAL gained approval for eslicarbazepine acetate from the European Commission on April 21, 2009 as adjunctive therapy in adult patients with partial-onset seizures with or without secondary generalisation. In Europe, the product is marketed under the trade name Zebinix. Aptiom is approved in Canada for use as adjunctive therapy in the treatment of partial-onset seizures in patients with epilepsy who are not satisfactorily controlled with conventional therapy.
Epilepsy is the fourth most common neurological condition, and one in 26 people in the US will develop epilepsy in their lifetime. Epilepsy manifests as unprovoked seizures, which are caused by abnormal firing of impulses from nerve cells in the brain. Partial-onset seizures, one type of seizure and the most common, are characterized by bursts of electrical activity that are initially focused in specific areas of the brain and may become more widespread, with symptoms varying according to the affected areas. The unpredictable nature of seizures can have a significant impact on those with epilepsy. Reducing the frequency of seizures can greatly lessen the burden of epilepsy. With approximately one-third of people living with epilepsy still unable to control seizures, there continues to be a need for new therapies. Up to 40 per cent of people living with epilepsy do not respond to the first or second monotherapy, and approximately 36 per cent do not have adequate control of seizures despite the use of two or more antiepileptic medications.