Cerliponase alfa
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Identification
- Summary
Cerliponase alfa is an enzyme replacement therapy used to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, also known as tripeptidyl peptidase 1 (TPP1) deficiency.
- Brand Names
- Brineura
- Generic Name
- Cerliponase alfa
- DrugBank Accession Number
- DB13173
- Background
Cerliponase alfa is a hydrolytic lysosomal N-terminal tripeptidyl peptidase-1 (TPP1).4 On April 27, 2017, cerliponase alfa was first approved by the FDA as the first treatment for neuronal ceroid lipofuscinosis type 2 (CLN2), also known as TPP1 deficiency.7 It was also approved by the EMA on May 30, 2017 5 and by Health Canada on December 19, 2018.6 CLN2 is a predominantly pediatric-onset neurodegenerative disease caused by a deficiency in the lysosomal enzyme TPP1, leading to progressive impairment in motor and cognitive function.1,3 As a recombinant human TPP1, cerliponase alfa is used as an enzyme replacement therapy to restore the levels of TPP1 in patients with CLN2.7
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Recombinant Enzymes - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 59000.0 Da (approximate)
- Sequences
>Cerliponase alfa protein sequence SYSPEPDQRRTLPPGWVSLGRADPEEELSLTFALRQQNVERLSELVQAVSDPSSPQYGKY LTLENVADLVRPSPLTLHTVQKWLLAAGAQKCHSVITQDFLTCWLSIRQAELLLPGAEFH HYVGGPTETHVVRSPHPYQLPQALAPHVDFVGGLHRFPPTSSLRQRPEPQVTGTVGLHLG VTPSVIRKRYNLTSQDVGSGTSNNSQACAQFLEQYFHDSDLAQFMRLFGGNFAHQASVAR VVGQQGRGRAGIEASLDVQYLMSAGANISTWVYSSPGRHEGQEPFLQWLMLLSNESALPH VHTVSYGDDEDSLSSAYIQRVNTELMKAAARGLTLLFASGDSGAGCWSVSGRHQFRPTFP ASSPYVTTVGGTSFQEPFLITNEIVDYISGGGFSNVFPRPSYQEEAVTKFLSSSPHLPPS SYFNASGRAYPDVAALSDGYWVVSNRVPIPWVSGTSASTPVFGGILSLINEHRILSGRPP LGFLNPRLYQQHGAGLFDVTRGCHESCLDEEVEGQGFCSGPGWDPVTGWGTPNFPALLKT LLNP
Download FASTA FormatReferences:
- KEGG DRUG: Cerliponase alfa [Link]
- Synonyms
- Cerliponase alfa
- Cerliponase alpha
- Immature cell growth-inhibiting gene 1 protein
- Immature human tripeptidyl-peptidase 1
- Immature lysosomal pepstatin-insensitive protease
- Immature tripeptidyl-peptidase I
- RECOMBINANT HUMAN TRIPEPTIDYL PEPTIDASE-1
- External IDs
- BMN 190
- BMN-190
- BMN190
Pharmacology
- Indication
Cerliponase alfa 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.4,5,6 It is approved for use in children in the US, whereas in Europe and Canada, it is approved for use in patients of all ages.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Neuronal ceroid lipofuscinosis type 2 •••••••••••• Management of Neuronal ceroid lipofuscinosis type 2 •••••••••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Cerliponase alfa is an enzyme replacement therapy that aims to supplement TPP1 deficiency 2 and attenuate the disease progression in CLN2.3
- Mechanism of action
CLN2 disease is a neurodegenerative disease associated with a variety of mutations leading to reduced activity or inactivation of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1),3 which removes tripeptides from the N-terminus of peptides in the central nervous system (CNS).2 TPP1 has no known substrate specificity.4 Deficiency in TPP1 activity results in the accumulation of ceroid lipofuscin in the lysosomes normally metabolized by TPP1 in the CNS, leading to massive glial activation and neuronal loss and a progressive decline in motor and cognitive function.3,4 Because TPP1 expression is developmentally controlled and peaks around the age of two to four, which is the onset of signs and symptoms of the classic late-infantile phenotype of CLN2 disease.3
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.1,2,4
Target Actions Organism NCation-independent mannose-6-phosphate receptor ligandHumans - Absorption
Cerliponase alfa pharmacokinetics have high inter-subject and intra-subject variability.4 Following intraventricular infusions of 300 mg of cerliponase alfa, the median maximum concentration (Cmax) in cerebrospinal fluid (CSF) was 1260, 1630 and 1390 ug/ml at day 1, week 5, and week 13, respectively. The median Tmax was 4.5, 4.3 and 4.3 h on day 1, week 5 and week 13, respectively. The area under the CSF concentration–time curve from 0 to the last measurable concentration (AUC0–t) 9290, 12,400 and 10,500 ug x h/ml, respectively.1,4
- Volume of distribution
Following intraventricular infusions of 300 mg of cerliponase alfa, the median CSF volume of distribution at steady state was 245, 196 and 186 ml on day 1, week 5 and week 13, respectively.1,4
- Protein binding
Not Available
- Metabolism
Cerliponase alfa is a protein and is expected to be degraded through peptide hydrolysis.4
- Route of elimination
Not Available
- Half-life
Following intraventricular infusions of 300 mg of cerliponase alfa, the median CSF half-life was 6.2, 7.4 and 7.7 hours on day 1, week 5 and week 13, respectively.1,4
- Clearance
Following intraventricular infusions of 300 mg of cerliponase alfa, the median CSF clearance was 32.3, 24.2 and 28.7 ml/h on day 1, week 5 and week 13, respectively.1,4
- Adverse Effects
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- Toxicity
There is no information available regarding the acute toxicity (LD50) and overdose of cerliponase alfa.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Brineura Solution 150 mg / 5 mL Intracerebral Biomarin International Limited 2019-03-18 Not applicable Canada Brineura Injection, solution; Kit 150 mg/5mL Intraventricular BioMarin Pharmaceutical Inc. 2017-04-27 Not applicable US Brineura Injection, solution 150 mg Intracerebral Biomarin International Limited 2020-12-23 Not applicable EU
Categories
- ATC Codes
- A16AB17 — Cerliponase alfa
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- X8R2D92QP1
- CAS number
- 151662-36-1
References
- General References
- Markham A: Cerliponase Alfa: First Global Approval. Drugs. 2017 Jul;77(11):1247-1249. doi: 10.1007/s40265-017-0771-8. [Article]
- Lewis G, Morrill AM, Conway-Allen SL, Kim B: Review of Cerliponase Alfa: Recombinant Human Enzyme Replacement Therapy for Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2. J Child Neurol. 2020 Apr;35(5):348-353. doi: 10.1177/0883073819895694. Epub 2019 Dec 29. [Article]
- Mole SE, Schulz A, Badoe E, Berkovic SF, de Los Reyes EC, Dulz S, Gissen P, Guelbert N, Lourenco CM, Mason HL, Mink JW, Murphy N, Nickel M, Olaya JE, Scarpa M, Scheffer IE, Simonati A, Specchio N, Von Lobbecke I, Wang RY, Williams RE: Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients. Orphanet J Rare Dis. 2021 Apr 21;16(1):185. doi: 10.1186/s13023-021-01813-5. [Article]
- FDA Approved Drug Products: BRINEURA (cerliponase alfa) injection, for intraventricular use (July 2024) [Link]
- EMA Approved Drug Products: Brineura (cerliponase alfa) Intracerebroventricular Infusion [Link]
- Health Canada Approved Drug Products: BRINEURA (cerliponase alfa) Intracerebroventricular Infusion (June 2020) [Link]
- FDA News Release: FDA approves first treatment for a form of Batten disease [Link]
- External Links
- KEGG Drug
- D10813
- PubChem Substance
- 347911440
- 1922436
- ChEMBL
- CHEMBL3544921
- Wikipedia
- Cerliponase_alfa
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Late-infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) 1 somestatus stop reason just information to hide Not Available Approved for Marketing Not Available Late-infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) 1 somestatus stop reason just information to hide 2 Completed Treatment Jansky-Bielschowsky Disease / Late-infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) / Neuronal Ceroid Lipofuscinosis 1 somestatus stop reason just information to hide 1, 2 Active Not Recruiting Treatment Late-infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) 1 somestatus stop reason just information to hide 1, 2 Completed Treatment Jansky-Bielschowsky Disease / Late-infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) / Neuronal Ceroid Lipofuscinosis 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Intracerebral 150 mg Injection, solution Intracerebral; Parenteral 150 MG Injection, solution; kit Intraventricular 150 mg/5mL Solution Intracerebral 150 mg / 5 mL Solution Intracerebral 30 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Ligand
- General Function
- Mediates the transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes (PubMed:18817523, PubMed:2963003). Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex (PubMed:18817523, PubMed:2963003). The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer (PubMed:18817523). This receptor also binds IGF2 (PubMed:18046459). Acts as a positive regulator of T-cell coactivation by binding DPP4 (PubMed:10900005)
- Specific Function
- D-mannose binding
- Gene Name
- IGF2R
- Uniprot ID
- P11717
- Uniprot Name
- Cation-independent mannose-6-phosphate receptor
- Molecular Weight
- 274372.42 Da
References
- Meng Y, Sohar I, Wang L, Sleat DE, Lobel P: Systemic administration of tripeptidyl peptidase I in a mouse model of late infantile neuronal ceroid lipofuscinosis: effect of glycan modification. PLoS One. 2012;7(7):e40509. doi: 10.1371/journal.pone.0040509. Epub 2012 Jul 6. [Article]
- Markham A: Cerliponase Alfa: First Global Approval. Drugs. 2017 Jul;77(11):1247-1249. doi: 10.1007/s40265-017-0771-8. [Article]
- Lewis G, Morrill AM, Conway-Allen SL, Kim B: Review of Cerliponase Alfa: Recombinant Human Enzyme Replacement Therapy for Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2. J Child Neurol. 2020 Apr;35(5):348-353. doi: 10.1177/0883073819895694. Epub 2019 Dec 29. [Article]
- FDA Approved Drug Products: BRINEURA (cerliponase alfa) injection, for intraventricular use (July 2024) [Link]
Drug created at April 28, 2017 19:55 / Updated at October 18, 2024 22:26