by Isabella Colonna
For February we have selected Schulz A, Specchio N, de Los Reyes E, Gissen P, Nickel M, Trivisano M, Aylward SC, Chakrapani A, Schwering C, Wibbeler E, Westermann LM, Ballon DJ, Dyke JP, Cherukuri A, Bondade S, Slasor P, Cohen Pfeffer J. Safety and efficacy of cerliponase alfa in children with neuronal ceroid lipofuscinosis type 2 (CLN2 disease): an open-label extension study. Lancet Neurol. 2024 Jan;23(1):60-70. doi: 10.1016/S1474-4422(23)00384-8. PMID: 38101904.
Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare paediatric neurodegenerative disease caused by mutations in the tripeptidyl peptidase 1 gene (TPP1) and characterised by progressive loss of motor and language function starting at around 3 years of age. Cerliponase alfa enzyme replacement therapy has been approved in 2017 by the EMA and the FDA for treatment of CLN2 disease. The aim of this study was to assess the long-term efficacy and safety of this drug in patients with CLN2 disease.
This work reports the cumulative results of a primary 48-week, single-arm, open-label study and of the following 240-week open-label extension study with six months of follow-up. Eligible patients were children aged 3-16 years and with a genetically confirmed diagnosis of CLN2 disease; the treatment consisted in intracerebroventricular infusion of 300mg cerliponase alfa every 2 weeks. There was a historical control group which included patients with CLNS2 previously enrolled in the DEM-CHILD neuronal ceroid lipofuscinosis patient database.
Twenty-three patients completed the primary study receiving the treatment for a mean of 272.1 weeks and were enrolled in the extension study, but only 17 individuals completed the planned follow-up. In comparison to the historical untreated controls, patients who received the treatment were less likely to have an unreversed 2-point decline or a score of 0 in the combined motor and language domains of the CLN2 Clinical Rating Scale, they experienced a slower clinical progression and a reduction of frequency of tonic-clonic seizures. All patients had at least one adverse event and 21 reported a serious adverse event; however, none of the adverse events led to study discontinuations or death.
In summary, this study showed that long-term treatment with cerliponase alfa is associated with a significant slowing of motor and language decline in children with CLN2 disease and with acceptable safety and tolerability.