Add-on Xcopri Therapy Reduces Seizures in 4 Adults: Case Series
Study showed treatment helped patients who previously had limited results
Combining Xcopri (cenobamate) with existing antiseizure medications may significantly reduce the frequency of seizures in adults with Dravet syndrome, according to a report of four patients.
The oral medication — marketed as Ontozry in Europe — reduced the frequency of seizures in all four adults by more than 80% over a median follow-up of 14 months.
“We highlight [Xcopri] as an [antiseizure medication] that may lead to a clinically meaningful reduction of seizure frequency in adult patients with [Dravet syndrome],” researchers wrote, adding further studies are needed to determine if all patients will benefit from the medication.
The study, “Successful treatment of adult Dravet syndrome patients with cenobamate,” was published in the journal Epilepsia.
Dravet syndrome is a severe type of epilepsy that often manifests in the first year of life. It is marked by episodes of prolonged seizures, cognitive impairments, and poor muscle coordination.
The majority of Dravet syndrome cases are caused by mutations in the SCN1A gene, which encodes a protein component of the sodium channel NAV1.1. This channel regulates the transport of sodium ions into nerve cells, allowing them to transmit nerve signals to other cells.
When NAV1.1 channels stop working due to mutations, a type of inhibitory neurons called GABA neurons becomes impaired, causing the nervous system to go into overdrive, become overactivated, leading to seizures.
Xcopri, developed by SK life science, is approved by the U.S. Food and Drug Administration to treat adults with partial seizures, which affect only a specific area of the brain. Its exact mode of action is unknown, but it is thought to act on GABA neurons, stimulating them to send silencing signals.
The medication also is thought to act on sodium channels that are persistently activated and promote an inactive state in these channels.
While therapies acting on sodium channels are not recommended for people with Dravet due to their potential to worsen seizures, a team of researchers from Germany now described the benefits of using Xcopri as an add-on therapy in four adults with Dravet syndrome carrying the SCN1A mutation.
Four patients with histories of seizures, limited results from therapies
The first patient was a 22-year-old man who experienced his first epileptic seizure following vaccination at 3 months. From the age of 1, he began experiencing prolonged seizures and generalized tonic-clonic seizures, characterized by convulsions with muscle jerks or other body movements, that continued into adolescence.
Before starting Xcopri, the patient had tried more than 12 antiseizure medications, including Onfi (clobazam), Depacon (valproic acid), and Keppra (levetiracetam), but the effects were limited. However, adding a daily dose of 250 mg of Xcopri to Keppra and Onfi reduced the frequency of his generalized seizures by 80% and the total number of seizures by more than 50%. The patient took Xcopri for 14 months and the only side effect was mild fatigue.
The second patient was a 27-year-old woman who experienced her first seizure at 4 months old, three days after vaccination. She began therapy with potassium bromide but continued to experience seizures monthly, some triggered by infections.
Until age 10, her seizures included brief jerking or twitching of muscles, stiffening of muscles without awareness, and night-time seizures. But at age 13, she began experiencing night-time seizures an average of five times a week. The seizures led to mental impairment, poor muscle tone, and movement difficulties.
The woman tried 14 antiseizure medications, steroid pulse therapy, and vagus nerve stimulation without lasting success. She started taking Xcopri at age 26, and with a final dose of 150 mg daily, her generalized seizures reduced from five per week to one per month — a seizure reduction of more than 80%. After taking Xcopri for more than 14 months, mild fatigue was the only side effect.
Patient three was a 26-year-old man who experienced his first generalized seizure at 8 months following a fever. He experienced other types of seizures throughout childhood, but only generalized seizures continued into adulthood.
The patient tried 17 antiseizure medications, but discontinued most of them due to side effects. He started taking a 200 mg daily dose of Xcopri at age 26, alongside Keppra and Depacon, and seizures were reduced from around 11 to two per month — a reduction of more than 80%. The man took Xcopri for more than 17 months without side effects.
The final patient was a 23-year-old man who experienced a first generalized seizure at 8 months. He developed movement and cognitive impairments, and a brain MRI scan performed at age 9 showed scarring on the left side of the brain. Treatment with 10 different epilepsy medications did not provide a satisfactory reduction in seizures.
The patient began taking Xcopri at age 22, alongside Depacon, Onfi, and Diacomit (stiripentol). After four months on a 200 mg daily dose of Xcopri, the patient had no seizures. He took the medication for more than 10 months without any side effects, and experienced only one generalized seizure per month.
“In all patients, [Xcopri] was the first [antiseizure medication] in their long disease histories to achieve significant seizure reduction over a long follow-up period. [Xcopri] was well tolerated with no serious adverse events. All patients continued on [Xcopri] at last follow-up,” the researchers wrote.
However, “due to the assumed mechanism of action, caution is required when initiating therapy with [Xcopri] in [Dravet syndrome] patients,” they concluded.
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