Banzel (rufinamide) — an approved add-on, anti-seizure oral therapy — is safe and effective in lowering seizure rates in children and adolescents with Lennox-Gastaut syndrome (LGS), according to a review study.
Nevertheless, researchers point out that future studies are needed to better assess the therapy’s effectiveness and provide optimized treatment approaches, as well as to clarify the timing and combination of Banzel with new anti-seizure therapies.
The review study, “Adjunctive Rufinamide in Children with Lennox-Gastaut Syndrome: A Literature Review,” was published in the journal Neuropsychiatric Disease and Treatment.
The characteristic presence of treatment-resistant seizures in LGS patients has a negative impact on patients’ development, quality of life, and survival.
Seizure management in these patients usually involves a combination of several anti-seizure therapies, including first-line valproate (brand name Convulex, Depakote, among others), lamotrigine, and topiramate, and second-line levetiracetam, clobazam, zonisamide, and Banzel.
Banzel, (marketed by Eisai and under the brand name Inovelon in Europe) is one of the latest approved anti-seizure therapies redirected toward LGS. Its mechanism of action involves the suppression of sodium channels’ activity in nerve cells in a way that distinguishes it from other anti-seizure therapies.
Researchers in Italy set out to review the therapeutic role of Banzel in LGS pediatric patients. They systematically analyzed published studies on Banzel’s effectiveness, safety profile, and its interaction with other anti-seizure therapies in children and adolescents with LGS, up to September 2019.
From a total of 333 studies, 23 were considered eligible. Most studies evaluated Banzel’s effects for up to three years.
Results showed that Banzel add-on treatment was associated with 26% to 65% reductions in seizure rates in LGS pediatric patients, which was superior to its effects in other treatment-resistant epileptic conditions.
Banzel was particularly effective in lowering the rates of spasms (by 99%), tonic seizures — those leading to sudden stiffness of the body, arms or legs — (by 73%), and drop seizures (by 50%) in LGS patients. Its effects on focal seizures — those starting at only one side of the brain — appeared to be more variable.
Also, exploratory analyses of clinical data highlighted that these benefits were associated with an improved quality of life in terms of the number of seizure-free days, with Banzel-treated patients reporting a 42.2% higher number of seizure-free days than those receiving a placebo.
Overall, the therapy showed a favorable safety profile, resulting mostly in mild adverse events. Common adverse events included vomiting, decreased appetite, somnolence (sleepiness), upper respiratory tract infections, mood changes, followed by constipation, diarrhea, seizures, and drowsiness.
The rate of Banzel discontinuations was up to 15% and associated with worsening of seizures or severe, but rare, adverse events. Data also suggested that Banzel-associated adverse events were dose-independent, supporting the close monitoring of Banzel’s effectiveness-safety balance to determine the best dose in each patient.
Given that Banzel can alter a person’s heartbeat, the researchers recommended that LGS patients on long-term Banzel treatment should be followed by a cardiologist.
Valproate was the mostly used anti-seizure therapy in these patients, followed by benzodiazepines, lamotrigine, topiramate, and levetiracetam. No specific combination of anti-seizure therapies that included Banzel seemed to be more effective in LGS patients.
The team noted that future studies assessing combination therapy responses in terms of seizure type and underlying cause of the disease could help to clarify the therapeutic effects of different treatment combinations.
Compared with older therapies, Banzel was considered to have an overall favorable interaction profile with other anti-seizure therapies.
Among newly approved therapies for LGS, Epidiolex was found to slightly increase the blood levels of Banzel. So, the researchers suggested that clinicians take this into consideration when prescribing this combination.
The team concluded that, overall, Banzel shows a very favorable profile in terms of safety and interactions with other anti-seizure therapies.
“Further studies are needed to clarify the interaction profile with the newest [anti-seizure treatments] for LGS and to assess correlations between the [underlying cause] of LGS and [therapy] response to individualize treatment and maximize efficacy,” the researchers wrote.