Intracerebroventricular Cerliponase Alfa (BMN 190) in Children with CLN2 Disease: Interim Results from a Phase 1/2, Open-Label, Dose-Escalation Study

Background: CLN2 disease, a rare, inherited, pediatric-onset, neurodegenerative lysosomal storage disorder caused by TPP1 enzyme deficiency, is characterized by seizures, ataxia, rapid loss of language and motor functions, blindness, and early death. Cerliponase alfa (BMN 190) is a recombinant human TPP1 enzyme. This phase 1/2, multicenter, open-label, dose-escalation study evaluated the safety, tolerability, and efficacy of every other week intracerebroventricular (ICV) infusions of cerliponase alfa in children with CLN2 aged 3 to 16 years.

Design/Methods: The first nine subjects were assigned to one of three cohorts in a dose escalation period (30, 100, 300 mg). All subjects were subsequently administered a stable dose of cerliponase alfa (300 mg) for at least 48 weeks. Efficacy was evaluated by monitoring changes in motor and language functions using a CLN2 clinical rating scale.

Results: A total of 24 subjects (9 male, 15 female, mean age 4.5 ± 1.2 years) enrolled in the study. All subjects had adverse events (AEs), the majority were Grade 1–2 and included pyrexia, hypersensitivity and convulsion. A total of 29 serious AEs (9 considered study drug-related), occurred in 15 subjects. There were no anaphylaxis/anaphylactoid reactions, study drug discontinuations or deaths due to AEs. In contrast to the 2.18 ± 1.07 units/year decline observed in the natural history, no net loss of function (p < 0.0001) was observed in the 13 subjects who completed at least 36 weeks of treatment.

Conclusion: Enzyme replacement therapy with ICV-administered cerliponase alfa is well-tolerated and slows the progression of functional decline in children with CLN2.