Cerliponase

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.

• 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. BRINEURA is a hydrolytic lysosomal N-terminal tripeptidyl peptidase 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.

• 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) ].contraindicated

Administration of BRINEURA should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. ( 2.1 ) BRINEURA should be administered by or under the supervision of a physician experienced in intraventricular administration. ( 2.1 ) Premedication of patients with antihistamines with or without antipyretics or corticosteroids is recommended. ( 2.1 ) Prior to each infusion, inspect the scalp for signs of intraventricular access device reservoir leakage, failure, or potential infection. ( 2.1 ) Recommended BRINEURA dosage is 300 mg administered once every other week as an intraventricular infusion. In patients less than 2 years of age, lower doses are recommended. ( 2.2 ) Dosing is not recommended in patients less than 37 weeks post-menstrual age or those weighing less than 2.5 kg. ( 2.2 ) See the full prescribing information for dosage modifications due to hypersensitivity reactions. ( 2.3 ) See the full prescribing information for preparation and administration instructions. ( 2.4 , 2.6 ) 2.1 Recommendations Prior to BRINEURA Treatment Administration of BRINEURA should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Initiate BRINEURA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment [see Warnings and Precautions (5.1) ] .

Meningitis and Other Intraventricular Access Device-Related Infections : Monitor the device insertion site for signs of infection. ( 4 , 5.2 ) Intraventricular Access Device-Related Complications : Consult a neurosurgeon for any complications with the implanted device. In case of device-related complication, discontinue the infusion and refer to the device labeling for further instructions. ( 4 , 5.3 ) Cardiovascular Adverse Reactions : Monitor vital signs before, during, and post-infusion. Monitor Electrocardiogram (ECG) in patients with a history of bradycardia, conduction disorder, or with structural heart disease, during the infusion. In patients without cardiac abnormalities, perform regular 12-lead ECG evaluations every 6 months. ( 2.5 , 5.4 ) Infusion-Associated Reactions (IARs) : If an IAR occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administering antihistamines and/or antipyretics may ameliorate the symptoms. ( 5.5 ) 5.1 Hypersensitivity Reactions Including Anaphylaxis Life-threatening hypersensitivity reactions including anaphylaxis have been reported in patients treated with enzyme replacement therapies, including BRINEURA . BRINEURA-treated patients have had these reactions occur in clinical studies and postmarketing use [see Adverse Reactions (6) ] . In clinical Trial 1 and Trial 2 to 96 weeks, a total of 11 of 24 (46%) patients experienced hypersensitivity reactions during the infusion or within 24 hours of completion of the infusion.

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) ] Most common adverse reactions (≥8%) are: pyrexia, ECG abnormalities, decreased CSF protein, vomiting, seizures, device-related complications, hypersensitivity, increased CSF protein, hematoma, headache, irritability, pleocytosis, device-related infections, bradycardia, feeling jittery, and hypotension. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact BioMarin at 1-866-906-6100 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Trial 1 and Trial 2 The safety of BRINEURA was evaluated in 24 patients with CLN2 disease who received at least one 300 mg dose of BRINEURA given by intraventricular infusion in a clinical trial with extension (Trials 1 and 2) of up to 161 weeks [see Clinical Studies (14) ] .

8.1 Pregnancy Risk Summary There are no available data on BRINEURA use in pregnant women to inform a drug-associated risk of pregnancy-related outcomes. Animal reproduction studies have not been conducted using cerliponase alfa. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. 8.2 Lactation Risk Summary There are no data on the presence of cerliponase alfa in human milk, the effects on the breastfed child, or the effects on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of BRINEURA to an infant during lactation; therefore, the development and health benefits of breastfeeding should be considered along with the mother's clinical need for BRINEURA and any potential adverse effects on the breastfed infant from BRINEURA or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of BRINEURA have been established to slow the loss of ambulation in pediatric patients with CLN2 disease and the information on this use is discussed throughout the labeling.

Metabolism

Patients 3 years of age and older The pharmacokinetics of cerliponase alfa were evaluated in patients with CLN2 disease who received intraventricular infusions of 30 mg (0.1 times the maximum approved recommended dosage), 100 mg (approximately 0.3 times the maximum approved recommended dosage), and 300 mg over approximately 4.5 hours once every other week. Cerliponase alfa CSF exposure following the initial single dose administration of BRINEURA increased less than proportionally across doses of 30 mg, 100 mg, and 300 mg.

• Apr 27, 2017BLABLA761052Biomarin Pharm

1. 1Pyrexia8817%
2. 2Seizure7515%
3. 3Vomiting367.1%
4. 4Device Related Infection295.7%
5. 5Device Leakage285.5%
6. 6Csf Culture Positive265.1%
7. 7Pneumonia224.3%
8. 8Headache203.9%
9. 9Drug Ineffective193.7%
10. 10Off Label Use173.3%
11. 11Nausea163.1%
12. 12Device Occlusion153.0%
13. 13Dystonia153.0%
14. 14General Physical Health Deterioration153.0%
15. 15Cough132.6%

The 7 most recently updated of 7 ClinicalTrials.gov registrations naming Cerliponase as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Intravitreal ERT to Prevent Retinal Disease Progression in Children With CLN2
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 5 enrolled · David L Rogers, MD
  NCT05152914updated 2026-04-30
• Cerliponase Alfa Observational Study in the US
  Active not recruiting · Observational · 35 enrolled · BioMarin Pharmaceutical
  NCT04476862updated 2026-01-14
• Examining Developmental Outcomes of Children Diagnosed With CLN2 Disease
  Enrolling by invitation · Observational · 30 enrolled · Jessica Scherr
  NCT03862274updated 2025-10-24
• A Safety, Tolerability, and Efficacy Study of BMN 190 in Pediatric Patients < 18 Years of Age With CLN2 Disease
  Completed · Phase 2 · Interventional · 14 enrolled · BioMarin Pharmaceutical
  NCT02678689updated 2025-02-17
• An Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 190 in Patients With CLN2 Disease
  Completed · Phase 1 · Phase 2 · Interventional · 23 enrolled · BioMarin Pharmaceutical
  NCT02485899updated 2022-08-24
• Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database
  Recruiting · Observational · 500 enrolled · Universitätsklinikum Hamburg-Eppendorf
  NCT04613089updated 2021-10-29
• A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Intracerebroventricular BMN 190 in Patients With Late-Infantile Neuronal Ceroid Lipofuscinosis (CLN2) Disease
  Completed · Phase 1 · Phase 2 · Interventional · 24 enrolled · BioMarin Pharmaceutical
  NCT01907087updated 2019-03-08

Frequently asked questions

How does Cerliponase work?

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.

What is Cerliponase used for?

According to FDA labeling, Cerliponase carries indications including: 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. BRINEURA is a hydrolytic lysosomal N-terminal tripeptidyl peptidase 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What are the brand names for Cerliponase?

Cerliponase is marketed under brand names including Brineura.

What are the contraindications for Cerliponase?

Cerliponase labeling lists contraindications including: 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) ].. Always consult the full prescribing information and a clinician.