Brineura (cerliponase alfa)
Drugs to Treat Neuronal Ceroid Lipofuscinosis type 2 (CLN2) Injection Kit; Injection Vial (ML)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Cerliponase alfa is a biosynthetic (recombinant DNA origin) form of human tripeptidyl peptidase-1 (TPP1), a lysosomal enzyme that catabolizes polypeptides in the CNS.
Cerliponase alfa is a biosynthetic (recombinant DNA origin) form of human tripeptidyl peptidase-1 (TPP1), a lysosomal enzyme that catabolizes polypeptides in the CNS. Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is caused by a deficiency of TPP1. TPP1 has no known substrate specificity; deficiency of the enzyme results in the accumulation of lysosomal storage materials in the CNS leading to progressive decline in motor function.
As an enzyme replacement therapy, cerliponase alfa is intended to replace the deficient endogenous enzyme in patients with CLN2 disease. Cerliponase alfa is a proenzyme; following intraventricular administration, the drug is taken up by target cells in the CNS and translocated to lysosomes through the cation independent mannose-6-phosphate receptor where it is then activated; the principal activity of the active (proteolytic) form of the enzyme is cleavage of tripeptides from the N-terminus of proteins.
Studies have shown extensive intrapatient and interpatient variability in the pharmacokinetics of cerliponase alfa. Following intraventricular administration of doses of 30, 100, and 300 mg in patients with CLN2 disease, CSF exposure of cerliponase alfa increased less than proportionally. There was no apparent accumulation of the drug in CSF or plasma when administered at a dosage of 300 mg once every other week.
Following single and multiple intraventricular doses of cerliponase alfa 300 mg every 2 weeks, CSF concentrations peaked at 15 minutes postinfusion and declined in a biphasic manner with a median half-life of approximately 7 hours. Plasma concentrations peaked at approximately 12 hours following the end of the infusion and declined in a biexponential manner. The estimated CSF volume of distribution following intraventricular infusion of 300 mg of cerliponase alfa exceeds the usual CSF volume of 100 mL.
Because cerliponase alfa is a protein, the drug is expected to be degraded through peptide hydrolysis.
Generic name: cerliponase alfa
Drug class: Drugs to Treat Neuronal Ceroid Lipofuscinosis type 2 (CLN2)
Therapeutic class: Metabolic Disease Enzyme Replacement Agents
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
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Indications
The following indications are listed for Brineura:
- Treatment To Slow Loss Of Ambulation In Late Infantile Neuronal Ceroid Lipofuscinosis Type 2
Also known as: Treatment To Slow Loss Of Ambulation In Tripeptidyl Peptidase 1 Deficiency, Treatment To Slow Motor Decline In Late Infantile Neuronal Ceroid Lipofuscinosis Type 2.
Dosing
The recommended dosage of cerliponase alfa in pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease is 300 mg once every other week by intraventricular infusion.
It is recommended that the first dose of cerliponase alfa be administered at least 5-7 days after implantation of the intraventricular access device.
Cerliponase alfa is administered directly into the CSF by intraventricular infusion via a surgically implanted intraventricular access device consisting of a reservoir (Codman(R) Holter Rickham reservoir) and catheter (Codman(R) ventricular catheter). The intraventricular access device must be implanted prior to (manufacturer recommends 5-7 days) administration of the first infusion. Infusions of cerliponase alfa should be administered using a controlled infusion device (B Braun Perfusor(R) Space infusion pump system).
Each infusion of cerliponase alfa should be followed by an infusion of intraventricular electrolytes (supplied by the manufacturer) to facilitate drug delivery and maintain patency of the intraventricular access device. Both cerliponase alfa and the electrolyte solution should be administered by intraventricular infusion at a rate of 2.5 mL/hour using the recommended syringe pump (B Braun Perfusor(R) Space infusion pump system); the duration of the complete infusion (cerliponase alfa plus the required infusion of intraventricular electrolytes) is approximately 4.5 hours. The complete infusion must be administered using an infusion set with a 0.2-mcm inline filter.
Proper aseptic technique must be strictly observed during preparation and administration of cerliponase alfa. Prior to use, vials of cerliponase alfa and intraventricular electrolytes should be stored upright in the freezer and kept in their original package to protect from light. The manufacturer-supplied administration kit (containing syringes, syringe needles, an extension line, infusion set with 0.2-mcm inline filter, and a port needle) should be stored separately from the drug and should not be frozen. Prior to intraventricular infusion, vials of cerliponase alfa and intraventricular electrolytes should be thawed at room temperature for approximately 60 minutes. The vials should not be thawed or warmed in any other way or shaken; condensation will occur during the thawing process. Commercially available cerliponase alfa injection for intraventricular use is a clear to slightly opalescent and colorless to pale yellow solution, and the intraventricular electrolytes injection is a clear to colorless solution. After the drug and electrolyte vials are completely thawed, they should be inspected visually for particulate matter or discoloration; the solutions should not be used if discoloration or particulate matter other than a few naturally occurring particles of the drug (e.g., thin translucent fibers or opaque particulate matter that is removed by the 0.2-mcm inline filter) are present. Vials containing intraventricular electrolytes also may contain particulate matter that may appear during the thawing period but should dissolve once the solution reaches room temperature. Cerliponase alfa and the intraventricular electrolytes solution should be used immediately once thawed; if not used immediately, unopened vials should be stored in the refrigerator at 2-8degreesC and used within 24 hours. Thawed solution should not be refrozen.
To prepare the cerliponase alfa solution for intraventricular infusion, a total of 10 mL should be withdrawn from two 5-mL vials of cerliponase alfa into a syringe; the syringe should be properly labeled to indicate that the contents contain cerliponase alfa. To prepare the electrolyte solution, a total of 2 mL should be withdrawn from the vial of intraventricular electrolytes into a syringe; the syringe should be properly labeled to indicate that the contents contain intraventricular electrolytes. Syringes should be used immediately following preparation. If not used immediately, the syringes should be stored in the refrigerator at 2-8degreesC and used within 4 hours. Vials of cerliponase alfa and intraventricular electrolytes are intended for single use only; any unused portions should be discarded. Cerliponase alfa should not be diluted or mixed with any other drug.
Prior to infusion, the patient's scalp should be inspected for signs of leakage or failure of the intraventricular access device and for potential infections; the scalp should be prepared for intraventricular infusion per institution standard of care. A total of 0.5-1 mL of CSF should be withdrawn to check patency of the intraventricular access device and the specimen should be sent for culture. (See Intraventricular Access Device-related Complications under Cautions: Warnings/Precautions.) The infusion system also should be inspected periodically during infusion for signs of leakage or delivery failure.
Following completion of the infusion, the infusion components, needles, unused solutions, and other waste materials should be disposed of in accordance with local requirements.
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Drug interactions
No formal drug interaction studies have been performed to date with cerliponase alfa.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Cerliponase alfa is contraindicated in patients with acute intraventricular access device-related complications (e.g., leakage, device failure, device-related infection) or ventriculoperitoneal shunts.
- Central nervous system infection
There are no severe contraindications for this drug.
- Bradycardia
- Structural disorder of heart
Adverse reactions
Adverse effects reported in 8% or more of patients receiving cerliponase alfa in clinical studies include pyrexia, ECG abnormalities, decreased CSF protein, vomiting, seizures, hypersensitivity, increased CSF protein, hematoma, headache, irritability, pleocytosis, device-related infection, bradycardia, feeling jittery, and hypotension.
More Frequent
- Abnormal ECG
- Hypersensitivity drug reaction
- Seizure disorder
Less Frequent
- Bradycardia
- Hypotension
- Infection
Rare or Very Rare
- Anaphylaxis
- Bacterial meningitis
- Hypoxia
- Tachycardia
More Frequent
- Decreased protein level in cerebrospinal fluid
- Elevated protein level in cerebrospinal fluid
- Fever
- Headache disorder
- Irritability
- Pleocytosis of cerebrospinal fluid
- Vomiting
Less Frequent
- Hematoma
- Nervousness
Rare or Very Rare
- Diarrhea
- Skin rash
Precautions
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Safety and efficacy of cerliponase alfa have not been established in pediatric patients younger than 3 years of age.
There are no adequate and well-controlled studies of cerliponase alfa in pregnant women. Animal reproduction studies with the drug have not been performed to date.
It is not known whether cerliponase alfa is distributed into human milk, affects milk production, or affects the breast-fed infant. The known benefits of breast-feeding should be considered along with the mother's clinical need for cerliponase alfa and any potential adverse effects of the drug or disease on the infant.
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ICD codes
| Code | Type | Description |
|---|---|---|
| Treatment to slow loss of ambulation in late infantile neuronal ceroid lipofuscinosis type 2 | ||
| E75.4 | ICD10CM | Neuronal ceroid lipofuscinosis |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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