Long-term safety and efficacy of intracerebroventricular enzyme replacement therapy with cerliponase alfa in children with CLN2 disease: two year results from an ongoing multicenter extension study
Abstract number :
2.191
Submission category :
4. Clinical Epilepsy / 4C. Clinical Treatments
Year :
2017
Submission ID :
346413
Source :
www.aesnet.org
Presentation date :
12/3/2017 3:07:12 PM
Published date :
Nov 20, 2017, 11:02 AM
Authors :
Emily de los Reyes, Nationwide Children’s Hospital, The Ohio State University, Columbus, OH, USA; Angela Schulz, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Nicola Specchio, Bambino Gesù Children’s Hospital, IRCCS, Rome, I
Rationale: CLN2 disease, a rare, inherited, pediatric, neurodegenerative lysosomal storage disorder caused by TPP1 deficiency, is characterized by seizures, language and motor function loss, blindness and early death. A phase 1/2 study (NCT01907087) demonstrated that intracerebroventricular (ICV) infusion of 300 mg cerliponase alfa, a recombinant human TPP1 enzyme, every other week for 48 weeks slowed deterioration in motor and language function. This extension study (NCT02485899) assesses the long-term safety and efficacy of ICV-administered cerliponase alfa in children with CLN2 disease for up to 240 weeks. Methods: Subjects who completed the phase 1/2 study continued receiving 300 mg cerliponase alfa every other week in this open-label extension study. Cumulative data from both studies were used to evaluate long-term safety (assessed by adverse events (AEs) frequency) and efficacy (assessed by changes in the CLN2 clinical rating scale motor and language (ML) domains). Results: 24 subjects (safety population) were initially treated with cerliponase alfa in the phase 1/2 study (9 male, 15 female, mean (SD) age 4.3 years (1.24)); 23 subjects (efficacy population) enrolled in the extension study (96 to 161 weeks total exposure, median 116 weeks). All had AEs; most were Grade 1-2. Common AEs included pyrexia, vomiting, and convulsion. Twenty (83%) subjects had at least one serious AE, which were mostly consistent with neurodegenerative disease in a pediatric population. Significant attenuation of the rate of decline in ML score (mean (95% CI): 0.27 (0.12, 0.42) points/ 48 weeks, p < 0.0001) was observed compared with a rate of decline of 2.0 points/48 weeks in untreated patients. The responder ( < 2 point loss per 48 weeks) rate at 96 weeks (100%, p < 0.0001) was improved compared to that observed at 48 weeks, suggesting a persistent treatment effect. Conclusions: These data suggest that enzyme replacement therapy with ICV-administered cerliponase alfa has an acceptable safety profile and a sustained treatment effect over time. Funding: BioMarin Pharmaceutical Inc.
Clinical Epilepsy