Brineura® (cerliponase alfa) is the only treatment that directly addresses the cause of CLN2 disease by replacing the TPP1 enzyme

Brineura® (cerliponase alfa) is a type of treatment called enzyme replacement therapy. Brineura helps to replace the TPP1 enzyme, the enzyme that is missing or not working properly in children with CLN2 disease.

Brineura was evaluated in 24 children with CLN2 disease in a clinical study with extension1

Each child’s ability to walk, with or without assistance, was evaluated over approximately 2 years. Their results were compared to records of untreated patients who experienced the rapid, predictable loss of mobility that occurs in CLN2 disease.1

Patients in the Brineura clinical study1

Children in the study ranged from 3 to 8 years old. The average age at first symptom was3.4 years (ranged from 2.5 to 6.3 years)1,2

Children in the extension study were evaluated at approximately 2 years; the study is still ongoing1

The CLN2 Clinical Rating Scale was used to measure how Brineura works1,*

Children’s ability to walk and crawl was measured using the CLN2 Clinical Rating Scale. Scores range from 3 (normal) to 0 (loss of walking/crawling abilities).1 Within each score, there may be some differences in the way each child shows their ability to walk or crawl.

Brineura helped maintain children’s ability to walk, with or without assistance, over approximately 2 years of treatment1

In the clinical study, decline was defined as a sustained drop of 2 points or a score o 0 on the CLN2 Clinical Rating Scale.1

  • The only Brineura-treated patient who experienced a significant decline in their ability to walk or crawl discontinued from the study after 1 infusion1
  • Ten children treated with the full dose of Brineura dropped 1 point on the CLN2 Clinical Rating Scale

Layla is a patient with CLN2 disease. She's been on treatment with Brineura since 2015

“ Layla is touching lives—not only has she touched other people’s lives, I feel like she’s made me a better person. I feel like I’m way more empathetic…Learning and going through this is something that really makes you realize what’s important.”

—Maria, Layla's mom

Possible side effects of Brineura1

Like all medicines, Brineura can cause side effects. Talk to your healthcare team immediately if your child experiences any side effects.

The most common side effects reported during Brineura infusions included1:

  • Fever
  • Problems with the electrical activity of the heart
  • Decreased or increased protein in the fluid of the brain
  • Vomiting
  • Seizures
  • Allergic reaction (hypersensitivity)
  • Collection of blood outside of blood vessels (hematoma)
  • Headache
  • Irritability
  • Increased white blood cell count in the fluid of the brain
  • Device-related infection
  • Slow heart rate
  • Feeling jittery
  • Low blood pressure

If your child is acting differently or if you have any concerns, talk to your healthcare team immediately.

Discover the path toward treatment with Brineura

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References: 1. Brineura [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2017. 2. Data on file, BioMarin Pharmaceutical Inc. 3. Steinfeld R, Heim P, von Gregory H, et al. Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations. Am J Med Genet. 2002;112:347-354.

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
Brineura is contraindicated in patients with acute intraventricular access device-related complications and with ventriculoperitoneal shunts.
Brineura must only be administered via the intraventricular route and using aseptic technique to reduce the risk of infection. Healthcare professionals should inspect the scalp for skin integrity to ensure the intraventricular access device is not compromised prior to each infusion. Brineura is contraindicated if there are signs of acute intraventricular access device-related complications (e.g., leakage, device failure or signs of device-related infection such as swelling, erythema of the scalp, extravasation of fluid, or bulging of the scalp around or above the intraventricular access device). In case of intraventricular access device complications, discontinue the Brineura infusion and refer to the manufacturer’s labeling for further instructions. Routinely send cerebrospinal fluid (CSF) samples for testing to detect subclinical device infections.
Material degradation of the intraventricular access device reservoir may occur after approximately 105 perforations of the intraventricular access device and may require replacement as soon as, or prior to, 105 administrations of Brineura.
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.
Hypotension occurred in 2 patients during or up to 8 hours after Brineura infusion. Patients did not require alteration in treatment, and reactions resolved spontaneously or after intravenous fluid administration.
One patient experienced hypoxia 8 hours after Brineura infusion, followed by a low mean arterial pressure at 15 hours post infusion. Symptoms resolved after oxygen administration, airway repositioning, and normal saline infusion. One patient reported decreased oxygen saturation, 45 minutes after starting Brineura, with associated low diastolic blood pressure. Hypoxia resolved after oxygen administration. No treatment was administered for the low diastolic blood pressure, which returned to normal while the patient continued to receive Brineura infusion without change to the infusion rate or dose.
Due to the potential for anaphylaxis, appropriate medical support should be readily available when Brineura is administered. If anaphylaxis occurs, immediately discontinue the infusion and initiate appropriate medical treatment. Observe patients closely during and after the infusion.
Hypersensitivity reactions were reported in 11 patients during or within 24 hours after completion of the Brineura infusion. The signs and symptoms observed concomitantly with hypersensitivity reactions include pyrexia, vomiting, pleocytosis, or irritability. Patients were routinely premedicated with antihistamines with or without antipyretics or corticosteroids, prior to infusion of Brineura.
The management of hypersensitivity reactions should be based on the severity of the reaction and may include temporarily interrupting the infusion, and/or treatment with antihistamines, antipyretics, and/or corticosteroids. If a severe hypersensitivity reaction occurs, immediately discontinue the infusion and initiate appropriate medical treatment.
Brineura has not been studied in pregnancy or lactation.
Safety and effectiveness in pediatric patients below 3 years of age have not been established.
In clinical trials, the most frequently reported adverse reactions (≥8%) were pyrexia, ECG abnormalities, CSF protein decreased, vomiting, seizures, hypersensitivity, CSF protein increased, hematoma, headache, irritability, pleocytosis, device-related infection, bradycardia, feeling jittery, and hypotension.
Seizures were reported in 12 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.
Device-related adverse reactions were reported in 12 patients and included infection, delivery system–related complications, and pleocytosis. Intraventricular access device-related CNS infections were observed in 2 patients. In both cases, antibiotics were administered, the intraventricular access device was replaced, and treatment continued. Devicerelated complications did not result in discontinuation of Brineura treatment. Other device-related adverse reactions included 1 patient with leakage of the intraventricular access device and 1 with 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 (33.3%) in patients treated with Brineura. No association was found between serum or CSF ADA titers and incidence or severity of hypersensitivity.
Inform caregivers of the signs and symptoms of anaphylaxis, hypotension, bradycardia, and device-related complications. Instruct them to seek immediate medical care should any of these signs and symptoms occur.
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 full Prescribing Information
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
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 were observed with Brineura treatment. If any signs of infection occur, contact your child’s doctor immediately. Your child’s intraventricular access device may need to be replaced over time.
Brineura should not be used in patients with active intraventricular access device-related complications (e.g., leakage, device failure, or device-related infection) and with shunts used to drain extra fluid around the brain.
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 FDA at 1-800-FDA-1088.
Please see full Prescribing Information