Persistent Treatment Effect of Cerliponase Alfa in Children with CLN2 Disease: A 3 Year Update from an Ongoing Multicenter Extension Study

Background: 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. An open-label study 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 cerliponase alfa for up to 240 weeks.

Design: Subjects who completed the initial study continued receiving 300 mg cerliponase alfa q.o.w. 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 were treated with cerliponase alfa in the open-label study (9 male, 15 female, mean (SD) age 4.3 years (1.24)); 23 subjects enrolled in the extension study (162 to 239 weeks treatment, median 193.7 weeks); 22 remained on study for at least 168 weeks. Common AEs included pyrexia, vomiting, and convulsion. Fewer subjects reported convulsions over time (21 (88%) during the first 24 weeks of therapy vs 6 (26%) during the last 24 weeks). Twenty (83%) subjects experienced serious AEs including hypersensitivity and device-related infections. The responder rate (< 2 points loss in motoric speech score per 48 weeks) after 160 weeks was 83% (p = 0.0013). The score decrease rate (mean (95% CI): 0.20 (0.10, 0.30) points / 48 weeks, p < 0.0001) was significantly lower compared to a decrease rate of 2.0 points / 48 weeks in untreated patients and has improved since previous analysis after 48 weeks (0.40 points / 48 weeks).

Conclusions: These data suggest that enzyme replacement therapy with intracerebroventricular cerliponase alfa has an acceptable safety profile and a sustained treatment effect.

Reference

1. Schulz A, Ajayi T, Specchio N, et al; CLN2 Study Group. Study of intraventricular cerliponase alfa for CLN2 disease. N Engl J Med 2018;378(20):1898–1907

 

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