Cerliponase Alfa (1 brand name, 1 dosage form, 1 route)
Available dosage forms: INJECTABLE.
Routes of administration: INJECTION.
Brand Names
- BRINEURA
Boxed Warning
Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate BRINEURA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue BRINEURA and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1)].
Indications and Usage
BRINEURA is 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.
Contraindications
BRINEURA is contraindicated in patients with: any sign or symptom of acute, unresolved localized infection on or around the device insertion site (e.g., cellulitis or abscess); or suspected or confirmed CNS infection (e.g., cloudy CSF or positive CSF gram stain, or meningitis) [see Warnings and Precautions (5.2)]. any acute intraventricular access device-related complication (e.g., leakage, extravasation of fluid, or device failure) [see Warnings and Precautions (5.3)]. ventriculoperitoneal shunts.
Adverse Reactions
The following adverse reactions are described below and elsewhere in the labeling: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.1)] Meningitis and Other Intraventricular Access Device-Related Infections [see Warnings and Precautions (5.2)] Intraventricular Access Device-Related Complications [see Warnings and Precautions (5.3)] Cardiovascular Adverse Reactions [see Warnings and Precautions (5.4)] Infusion-Associated Reactions [see Warnings and Precautions (5.5)]
Mechanism of Action
CLN2 disease is a neurodegenerative disease caused by deficiency of the lysosomal enzyme tripeptidyl peptidase-1 (TPP1), which catabolizes polypeptides in the CNS. TPP1 has no known substrate specificity. Deficiency in TPP1 activity results in the accumulation of lysosomal storage materials normally metabolized by this enzyme in the central nervous system (CNS), leading to progressive decline in motor function. Cerliponase alfa (rhTTP1), a proenzyme, is taken up by target cells in the CNS and is translocated to the lysosomes through the Cation Independent Mannose-6-Phosphate Receptor (CI-MPR, also known as M6P/IGF2 receptor). Cerliponase alfa is activated in the lysosome and the activated proteolytic form of rhTPP1 cleaves tripeptides from the N-terminus of proteins.