Seizures In Children With Cln2 Disease Receiving Cerliponase Alfa For >5 Years

Long-term intracerebroventricular administration of 300 mg cerliponase alfa every 2 weeks has been shown to slow deterioration in motor and language function in children with CLN2 disease. Seizures also present a significant burden throughout disease progression. We report data on the incidence of seizures in subjects treated with cerliponase alfa for >5 years.

Subjects who received 300 mg cerliponase alfa for up to 240 weeks in an open-label extension study were considered. Change from baseline in the seizure domain score of the CLN2 Clinical Rating scale among treated subjects was compared to natural history controls. The number of treated subjects reporting ≥1 adverse event (AE) of convulsions was assessed for each 24-week period of follow-up.

A total of 24 subjects were enrolled in the primary study (mean [SD] age: 4.9 [1.3] years); 23 subjects continued to receive cerliponase alfa in the extension (mean [range] exposure: 272 [162–300] weeks). Mean (SD) seizure (generalized tonic-clonic) score increased, representing improvement, from 1.7 (1.2) at baseline to 2.4 (0.8) at week 289 in treated subjects and decreased from 1.7 (1.1) to 0.7 (1.2) in natural history controls. The proportion of treated subjects reporting ≥1 AE of convulsions declined from 88% (n=21) in weeks 0-24 to 59% (n=13) in weeks >216.

These results suggest that there may be a reduction in the incidence of seizures over time in subjects receiving cerliponase alfa treatment. Further evaluation will be required to assess the impact of disease progression, anti-seizure medication use, and impact on other seizure types.