Regulatory Decision Summary for Banzel

This submission proposes to expand the currently approved indication to include patients 1 to less than 4 years of age. The current indication in patients 4 years of age and older was supported by a small but well-controlled study of 74 patients in the rufinamide arm (Placebo: 64 patients), which yielded positive efficacy data. Currently, Lamictal (lamotrigine) is approved for adjunctive treatment of patients >9 kg with Lennox-Gastaut Syndrome (LGS). This disease is one of the most devastating childhood epilepsies with an incidence of approximately 0.5 - 2 per 10,000. Some patients could experience 1,000s of attacks per year, including major seizures (generalized tonic-clonic, drop attacks). Patients are difficult to recruit into trials and carry to study completion. Thus, LGS trials are typically small (few arms) and have a low number of patients. Due to these limitations, and the fact that LGS is rare disease and very difficult to treat, flexibility is shown in order to include as much information in the PM despite the fact that study 303 was not designed nor adequately powered to demonstrate efficacy for this particular age group (1 to <4 years). This approach will provide prescribers with the available data, allowing for a more informed and sound clinical judgement in treating their patients.

Despite the fact that plasma levels of rufinamide appear to be similar across all pediatric age groups (1 to 17 years), efficacy was not clearly demonstrated in this particular population (1 to <4 years of age). Thus, rufinamide PM has been amended to provide a description of study 303 and state the facts on safety, efficacy and pharmacokinetics. All other safety issues, known to Health Canada at this time, are labelled properly and risks can be managed.