Drug updated on 10/30/2024
| Dosage Form | Injection (intraventricular; 150 mg/5 mL [30 mg/mL]) |
| Drug Class | Hydrolytic lysosomal N-terminal tripeptidyl peptidases |
| Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- Indicated to slow the loss of ambulation in pediatric patients with neuronal ceroid lipofuscinosis type 2 (CLN2 disease), also known as tripeptidyl peptidase 1 (TPP1) deficiency.
Latest News
Summary
- This summary is based on the review of three systematic review(s)/meta-analysis(es). [1-3]
- Cerliponase alfa demonstrated significant effectiveness in improving quality of life in children with CLN2 disease, with a strong correlation between the Motor domain of the Clinical Rating Scale and the Physical domain of the PedsQL, highlighting motor function as a key factor in patient quality of life.
- In a Phase I/II study, the pharmacokinetics of cerliponase alfa showed no drug accumulation in CSF or plasma with biweekly dosing of 300 mg. No correlation was found between drug levels and adverse events or antidrug antibodies, indicating the dose provided maximum benefit across the range of exposures.
- The safety profile of cerliponase alfa in children with CLN2 disease included adverse events such as pyrexia, hypersensitivity, seizures, and epilepsy. However, there was no apparent correlation between drug exposure levels in CSF or plasma and the incidence of these adverse events.
- The presence of antidrug antibodies in CSF and serum did not correlate with the occurrence of adverse events, indicating that antibody formation did not significantly impact the safety profile.
- The population types included 23 children with CLN2 disease treated with cerliponase alfa for ≥96 weeks and 24 patients aged ≥3 years. No correlation was observed between baseline demographics (sex, age, weight, and disease severity) and pharmacokinetics, indicating consistent drug exposure across pediatric subgroups. Motor function showed the highest correlation with quality of life in children.
Product Monograph / Prescribing Information
| Document Title | Year | Source |
|---|---|---|
| Brineura (cerliponase alfa) Prescribing Information. | 2024 | Pfizer Inc., New York, NY |
Systematic Reviews / Meta-Analyses
| Document Title | Year | Source |
|---|---|---|
| Exploring concurrent validity of the CLN2 Clinical Rating Scale: Comparison to PedsQL using cerliponase alfa clinical trial data | 2024 | PloS One |
| Dose selection for intracerebroventricular cerliponase alfa in children with CLN2 disease, translation from animal to human in a rare genetic disease | 2021 | Clinical and Translational Science |
| Clinical Pharmacokinetics and Pharmacodynamics of Cerliponase Alfa, Enzyme Replacement Therapy for CLN2 Disease by Intracerebroventricular Administration | 2021 | Clinical and Translational Science |
Clinical Practice Guidelines
| Document Title | Year | Source |
|---|---|---|
| HSE guidelines for the treatment of neuronal ceroid lipofuscinosis Type 2 (CLN2) with Cerliponase alfa (Brineura®) | 2024 | HSE Guidelines |
| Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients | 2021 | Orphanet Journal of Rare Diseases |
| Cerliponase alfa for treating neuronal ceroid lipofuscinosis type 2 | 2019 | National Institute for Health and Care Excellence |