Brineura (cerliponase alfa), an enzyme replacement, is the first and only product to treat CLN2 disease
Brineura (cerliponase alfa) injection for intraventricular use is indicated to slow the loss of ambulation in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency.
CLN2 disease is a rare and rapidly progressing childhood neurodegenerative disorder
CLN2 disease is one of the most common forms of neuronal ceroid lipofuscinoses (NCLs),1 also known as Batten disease.2 CLN2 disease is an autosomal recessive lysosomal storage disorder (LSD), and is associated with a predictable and rapid decline in function.1
Visit CLN2Connection.com to learn more about CLN2 disease >

Brineura helps replace the deficient tripeptidyl peptidase 1 (TPP1) enzyme in children with CLN2 disease3

Pathogenic variants (mutations) in the TPP1 gene (also referred to as the CLN2 gene) result in absence of or reduced activity of the TPP1 enzyme.4 This enzyme deficiency is associated with the neuronal degeneration observed in CLN2 disease.4
about-cell-01
Absence or reduced activity of the TPP1 enzyme is associated with an accumulation of storage material in the lysosome, which is associated with neuronal dysfunction and cell death.3,5
about-cell-02
Brineura is taken up into target cells and translocated to the lysosomes.3
about-cell-03
Brineura cleaves the lysosomal tripeptides and helps to clear accumulation in the cell.3
Brineura is contraindicated in patients with acute intraventricular access device-related complications and with ventriculoperitoneal shunts. Cardiovascular and hypersensitivity reactions related to Brineura may occur.
Brineura is an enzyme replacement therapy administered via intraventricular infusion
The use of intraventricular route ensures Brineura is delivered directly into the central nervous system. Intraventricular infusion has been used in clinical settings for over 50 years in adults and children, and is an established approach for delivery of drugs to the brain.6
Brineura is administered to the cerebrospinal fluid by infusion via a surgically implanted reservoir and catheter (intraventricular access device).3 The intraventricular access device must be surgically implanted prior to the first intraventricular infusion.3 It is recommended that the first dose be administered at least 5 to 7 days after device implantation.3
Brineura is contraindicated if there are signs of acute intraventricular access device-related complications. In case of intraventricular access device complications, discontinue the Brineura infusion and refer to the manufacturer’s labeling for further instructions.
Device-related adverse reactions were reported in 12 patients and included infection, delivery system related complications, and pleocytosis. Device-related complications did not result in discontinuation of Brineura treatment.
Brineura dosage
vials

The recommended dosage of Brineura in pediatric patients 3 years of age and older is 300 mg administered once every other week by intraventricular infusion.3 The complete Brineura infusion, including the required infusion of Intraventricular Electrolytes, is approximately 4.5 hours.3
Brineura should be administered under strict aseptic techniques. Administration protocols may vary by institution. Refer to your institution’s policies and procedures for guidance.
The care team prepares the patient and their family for infusion and what to expect during the infusion process. The child will be monitored before, during, and after the infusion. Pretreatment of patients with antihistamines with or without antipyretics or corticosteroids is recommended 30 to 60 minutes prior to the start of the infusion.
Perform electrocardiogram (ECG) monitoring during infusion in patients with a history of bradycardia, conduction disorder, or with structural heart disease, as some patients with CLN2 disease may develop conduction disorders or heart disease. In patients without cardiac abnormalities, regular 12-lead ECG evaluations should be performed every 6 months.
Learn more about Brineura administration by downloading a Dosing and Administration Guide >
View more helpful resources >
See Brineura efficacy results
The efficacy of Brineura was assessed over 96 weeks in a nonrandomized, single-arm clinical study with extension.
Next section >
References: 1. Mole SE, Williams RE. Neuronal ceroid-lipofuscinoses. 2001 Oct 10 [Updated 2013 Aug 1]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews . 2. Haltia M. The neuronal ceroid-lipofuscinoses: from past to present. Biochimica et Biophysica Acta. 2006;1762:850-856. 3. Brineura [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2020. 4. Schulz A, Kohlschutter A, Mink J, Simonati A, Williams R. NCL diseases clinical perspectives. Biochimica et Biophysica Acta. 2013;1832:1801-1806. 5. Vuillemenot B, Kennedy D, Cooper J, et al. Nonclinical evaluation of CNS-administered TPP1 enzyme replacement in canine CLN2 neuronal ceroid lipofuscinosis. Mol Genet Metab. 2015;114:281-293. 6. Cohen-Pfeffer JL, Gururangan S, Lester T, et al. Intracerebroventricular delivery as a safe, long-term route of drug administration. Pediatr Neurol. 2017;67:23-35.

Brineura® (cerliponase alfa), an enzyme replacement, is the first and only product to treat CLN2 disease

Brineura® (cerliponase alfa) injection for intraventricular use is indicated to slow the loss of ambulation in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency.

CLN2 disease is a rare and rapidly progressing childhood neurodegenerative disorder

CLN2 disease is one of the most common forms of neuronal ceroid lipofuscinoses (NCLs),1 also known as Batten disease.2 CLN2 disease is an autosomal recessive lysosomal storage disorder (LSD), and is associated with a predictable and rapid decline in function.1

Visit CLN2Connection.com to learn more about CLN2 disease >

Brineura helps replace the deficient tripeptidyl peptidase 1 (TPP1) enzyme in children with CLN2 disease3

Pathogenic variants (mutations) in the TPP1 gene (also referred to as the CLN2 gene) result in absence of or reduced activity of the TPP1 enzyme.4 This enzyme deficiency is associated with the neuronal degeneration observed in CLN2 disease.4
about-cell-01
Absence or reduced activity of the TPP1 enzyme is associated with an accumulation of storage material in the lysosome, which is associated with neuronal dysfunction and cell death.3,5
about-cell-02
Brineura is taken up into target cells and translocated to the lysosomes.3
about-cell-03
Brineura cleaves the lysosomal tripeptides and helps to clear accumulation in the cell.3
Brineura is contraindicated in patients with acute intraventricular access device-related complications and with ventriculoperitoneal shunts. Cardiovascular and hypersensitivity reactions related to Brineura may occur.

Brineura is an enzyme replacement therapy administered via intraventricular infusion

The use of intraventricular route ensures Brineura is delivered directly into the central nervous system. Intraventricular infusion has been used in clinical settings for over 50 years in adults and children, and is an established approach for delivery of drugs to the brain.6
Brineura is administered to the cerebrospinal fluid by infusion via a surgically implanted reservoir and catheter (intraventricular access device).3 The intraventricular access device must be surgically implanted prior to the first intraventricular infusion.3 It is recommended that the first dose be administered at least 5 to 7 days after device implantation.3
Brineura is contraindicated if there are signs of acute intraventricular access device-related complications. In case of intraventricular access device complications, discontinue the Brineura infusion and refer to the manufacturer’s labeling for further instructions.
Device-related adverse reactions were reported in 12 patients and included infection, delivery system–related complications, and pleocytosis. Device-related complications did not result in discontinuation of Brineura treatment.

Brineura dosage

vials_with_carton_us_xl_v03
The recommended dosage of Brineura in pediatric patients 3 years of age and older is 300 mg administered once every other week by intraventricular infusion.3 The complete Brineura infusion, including the required infusion of Intraventricular Electrolytes, is approximately 4.5 hours.3
Brineura should be administered under strict aseptic techniques. Administration protocols may vary by institution. Refer to your institution’s policies and procedures for guidance.
The care team prepares the patient and their family for infusion and what to expect during the infusion process. The child will be monitored before, during, and after the infusion. Pretreatment of patients with antihistamines with or without antipyretics or corticosteroids is recommended 30 to 60 minutes prior to the start of the infusion.
Perform electrocardiogram (ECG) monitoring during infusion in patients with a history of bradycardia, conduction disorder, or with structural heart disease, as some patients with 
CLN2 disease may develop conduction disorders or heart disease. In patients without cardiac abnormalities, regular 
12-lead ECG evaluations should be performed every 6 months.
Learn more about Brineura administration by downloading a Dosing and Administration Guide >

See Brineura efficacy results

The efficacy of Brineura was assessed over 96 weeks in a nonrandomized, single-arm clinical study with extension.

References: 1. Mole SE, Williams RE. Neuronal ceroid-lipofuscinoses. 2001 Oct 10 [Updated 2013 Aug 1]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews®. 2. Haltia M. The neuronal ceroid-lipofuscinoses: from past to present. Biochimica et Biophysica Acta. 2006;1762:850-856. 3. Brineura [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2020. 4. Schulz A, Kohlschütter A, Mink J, Simonati A, Williams R. NCL diseases – clinical perspectives. Biochimica et Biophysica Acta. 2013;1832:1801-1806. 5. Vuillemenot B, Kennedy D, Cooper J, et al. Nonclinical evaluation of CNS-administered TPP1 enzyme replacement in canine CLN2 neuronal ceroid lipofuscinosis. Mol Genet Metab. 2015;114:281-293. 6. Cohen-Pfeffer JL, Gururangan S, Lester T, et al. Intracerebroventricular delivery as a safe, long-term route of drug administration. Pediatr Neurol. 2017;67:23-35.

Indication
Brineura® (cerliponase alfa) injection for intraventricular use is indicated to slow the loss of ambulation in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency.
Important Safety Information
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)
  • any acute intraventricular access device-related complications (e.g., leakage, extravasation of fluid, or device failure)
  • ventriculoperitoneal shunts
Important Preparation and Administration Information
Brineura must only be administered via the intraventricular route using aseptic technique to reduce the risk of infection. Administer Brineura and the Intraventricular Electrolytes using the provided Administration Kit for use with Brineura components. Prior to each infusion, inspect the scalp for signs of intraventricular access device leakage or failure and for potential infection. Prior to each infusion of Brineura and when clinically indicated, send cerebrospinal fluid (CSF) samples for testing of cell count and culture.
Special Populations

Brineura has not been studied in pregnancy or lactation.

Safety and effectiveness in pediatric patients below 3 years of age have not been established.

WARNINGS AND PRECAUTIONS
Meningitis and Other Intraventricular Access Device-Related Infections
Bacterial meningitis requiring antibiotic treatment and removal of the device was reported during postmarketing use of Brineura. The signs and symptoms of infections may not be readily apparent in patients with CLN2 disease. To reduce the risk of infectious complications, Brineura should be administered by, or under the direction of, a physician experienced in intraventricular administration.
Intraventricular Access Device-Related Complications
During the clinical trial and in postmarketing reports, intraventricular access device-related complications were reported (e.g., device leakage, device failure, extravasation of CSF fluid, or bulging of the scalp around or above the intraventricular access device). In case of intraventricular access device-related complications, discontinue the Brineura infusion and refer to the device manufacturer’s labeling for further instructions.
Material degradation of the intraventricular access device reservoir was reported after approximately 4 years of administration, which may impact the effective and safe use of the device. The intraventricular access device should be replaced prior to 4 years of single-puncture administrations, which equates to approximately 105 administrations of Brineura.
Cardiovascular Adverse Reactions
Monitor vital signs before infusion starts, periodically during infusion, and post-infusion in a healthcare setting. Perform electrocardiogram (ECG) monitoring during infusion in patients with a history of bradycardia, conduction disorder, or with structural heart disease. In patients without cardiac abnormalities, regular 12-lead ECG evaluations should be performed every 6 months.
Hypersensitivity Reactions, Including Anaphylaxis
Hypersensitivity reactions, including anaphylaxis, have been reported in Brineura-treated patients during clinical studies and postmarketing use. In clinical trials, a total of 11 out of 24 patients (46%) experienced hypersensitivity reactions during the infusion or within 24 hours of completion of the infusion.
Due to the potential for anaphylaxis, appropriate medical support should be readily available when Brineura is administered. If a severe hypersensitivity reaction or anaphylaxis occurs, immediately discontinue the infusion and initiate appropriate medical treatment. Observe patients closely during and after the infusion. Inform patients/caregivers of the signs and symptoms of hypersensitivity reactions and anaphylaxis and instruct them to seek immediate medical care should signs and symptoms occur. Consider the risks and benefits of readministration of Brineura following an anaphylactic reaction.
ADVERSE REACTIONS
In clinical trials, the most frequently reported adverse reactions (≥8%) were pyrexia, ECG abnormalities, decreased CSF protein, vomiting, seizures, device-related complications, hypersensitivity, increased CSF protein, hematoma, headache, irritability, pleocytosis, device-related infection, bradycardia, feeling jittery, and hypotension.
Seizures were reported in 12 of 24 patients and included atonic, generalized tonic-clonic, focal, and absence. Seizures were managed with standard anticonvulsive therapies and did not result in discontinuation of Brineura treatment.
Adverse reactions related to the device were observed in 12 of 24 patients. Device-related adverse reactions include infection, delivery system-related complications, and pleocytosis.
Hematoma adverse reactions were reported in 5 patients and presented as hematoma, post-procedural hematoma, traumatic hematoma, and subdural hematoma. Hematomas did not require treatment and did not interfere with Brineura infusion.
Anti-drug antibodies (ADAs) were detected in serum (79%) and CSF (33%) in patients treated with Brineura. No association was found between serum or CSF ADA titers and incidence or severity of hypersensitivity.
To report SUSPECTED ADVERSE REACTIONS, contact BioMarin Pharmaceutical Inc. at 1-866-906-6100, or FDA at 1-800-FDA-1088, or go to www.fda.gov/medwatch.
Please see accompanying full Prescribing Information, or visit www.Brineura.com.
Indication
Brineura® (cerliponase alfa) is a prescription medication used to slow loss of ability to walk or crawl (ambulation) in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency.
Important Safety Information
Brineura is a prescription medicine. Before treatment with Brineura, it is important to discuss your child’s medical history with their doctor. Tell the doctor if they are sick or taking any medication and if they are allergic to any medicines. Your child’s doctor will decide if Brineura is right for them. If you have questions or would like more information about Brineura, contact your child’s doctor.
Brineura is only given by infusion into the fluid of the brain (known as an intraventricular injection) and using sterile technique to reduce the risk of infection. An intraventricular access device or port must be in place at least 5 to 7 days prior to the first infusion. Intraventricular access device-related infections, including meningitis, were observed with Brineura treatment. If any signs of infection or meningitis occur, contact your child’s doctor immediately. The signs and symptoms of infections may not be readily apparent in patients with CLN2 disease. Your doctor should vigilantly be looking for signs and symptoms of infection, including meningitis, during treatment with Brineura.
Your child’s intraventricular access device should be replaced prior to 4 years of single-puncture administration of Brineura, because the device may deteriorate due to repeated use.
Brineura should not be used in patients with active intraventricular access device-related complications (e.g., leakage, device failure, or device-related infection, including meningitis), symptom of acute, unresolved localized infection around the device insertion site (e.g. cellulitis or abscess), or and with shunts used to drain extra fluid around the brain. Your child’s doctor should inspect the scalp and collect samples of your child’s cerebrospinal fluid (CSF) prior to each infusion of Brineura, to check that there is no device failure or infections present.
Low blood pressure and/or slow heart rate may occur during and following the Brineura infusion. Contact your child’s doctor immediately if these reactions occur.
Undesirable or hypersensitivity reactions related to Brineura treatment, including fever, vomiting, and irritability, may occur during treatment and as late as 24 hours after infusion. Your child may receive medication such as antihistamines before Brineura infusions to reduce the risk of reactions. Serious and severe allergic reactions (anaphylaxis) may occur. If a reaction occurs, the infusion will be stopped and your child may be given additional medication. If a severe reaction occurs, the infusion will be stopped and your child will receive appropriate medical treatment. If any signs of anaphylaxis occur, immediately seek medical care.
Safety and effectiveness in pediatric patients below 3 years of age have not been established.
The most common side effects reported during Brineura infusions included fever, problems with the electrical activity of the heart, decreased or increased protein in the fluid of the brain, vomiting, seizures, hypersensitivity, collection of blood outside of blood vessels (hematoma), headache, irritability, and increased white blood cell count in the fluid of the brain, device-related infection, slow heart rate, feeling jittery, and low blood pressure. Intraventricular device-related side effects included infection, delivery system-related complications, and increased white blood cell count in fluid of the brain.
These are not all of the possible side effects with Brineura. Talk to your child’s doctor if they have any symptoms that bother them or that do not go away.
Call your doctor for medical advice about side effects. You may report side effects to BioMarin Pharmaceutical Inc. at 1-866-906-6100, or the FDA at 1-800-FDA-1088 or go to www.fda.gov/medwatch.
Please see accompanying full Prescribing Information, or visit www.Brineura.com.