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Kim A, Grover A, Hammon K, et al. Clinical Pharmacokinetics and Pharmacodynamics of Cerliponase Alfa, Enzyme Replacement Therapy for CLN2 Disease by Intracerebroventricular Administration. Clin Transl Sci. 2020;14(2):635-644doi: 10.1111/cts.12925.
Kim, A., Grover, A., Hammon, K., de Hart, G., Slasor, P., Cherukuri, A., Ajayi, T., Jacoby, D., Schulz, A., Specchio, N., de Los Reyes, E., Gissen, P., & Henshaw, J. W. (2021). Clinical Pharmacokinetics and Pharmacodynamics of Cerliponase Alfa, Enzyme Replacement Therapy for CLN2 Disease by Intracerebroventricular Administration. Clinical and translational science, 14(2), 635-644. https://doi.org/10.1111/cts.12925
Kim, Aryun, et al. "Clinical Pharmacokinetics and Pharmacodynamics of Cerliponase Alfa, Enzyme Replacement Therapy for CLN2 Disease by Intracerebroventricular Administration." Clinical and translational science vol. 14,2 (2021): 635-644. doi: https://doi.org/10.1111/cts.12925
Kim A, Grover A, Hammon K, de Hart G, Slasor P, Cherukuri A, Ajayi T, Jacoby D, Schulz A, Specchio N, de Los Reyes E, Gissen P, Henshaw JW. Clinical Pharmacokinetics and Pharmacodynamics of Cerliponase Alfa, Enzyme Replacement Therapy for CLN2 Disease by Intracerebroventricular Administration. Clin Transl Sci. 2021 Mar;14(2):635-644. doi: 10.1111/cts.12925. Epub 2020 Nov 30. PMID: 33202105; PMCID: PMC7993266.
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Clin Transl Sci. 2021 Mar;14(2):635-644. doi: 10.1111/cts.12925. Epub 2020 Nov 30.

Clinical Pharmacokinetics and Pharmacodynamics of Cerliponase Alfa, Enzyme Replacement Therapy for CLN2 Disease by Intracerebroventricular Administration.

Clinical and translational science

Aryun Kim, Anita Grover, Kevin Hammon, Greg de Hart, Peter Slasor, Anu Cherukuri, Temitayo Ajayi, David Jacoby, Angela Schulz, Nicola Specchio, Emily de Los Reyes, Paul Gissen, Joshua W Henshaw

Affiliations

  1. BioMarin Pharmaceutical Inc., Novato, California, USA.
  2. University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  3. Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
  4. Nationwide Children's Hospital and Ohio State University, Columbus, Ohio, USA.
  5. NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK.

PMID: 33202105 PMCID: PMC7993266 DOI: 10.1111/cts.12925

Abstract

Cerliponase alfa is recombinant human tripeptidyl peptidase 1 (TPP1) delivered by i.c.v. infusion for CLN2, a pediatric neurodegenerative disease caused by deficiency in lysosomal enzyme TPP1. We report the pharmacokinetics (PK) and pharmacodynamics of cerliponase alfa, the first i.c.v. enzyme replacement therapy, characterized in a phase I/II study. Escalating doses (30-300 mg Q2W) followed by 300 mg Q2W for ≥ 48 weeks were administered in 24 patients aged ≥ 3 years. Concentrations peaked in cerebrospinal fluid (CSF) at the end of ~ 4-hour i.c.v. infusion and 8 hours thereafter in plasma. Plasma exposure was 300-1,000-fold lower than in CSF, with no correlation in the magnitude of peak concentration (C

© 2020 BioMarin. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.

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