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Brineura® (cerliponase alfa) clinical study: Design and demographics

Brineura was assessed over 96 weeks in a nonrandomized, single-arm study with extension vs a natural history cohort1,2

Clinical Study chart
  • 24 patients, aged 3 to 8 years, were treated with Brineura® (cerliponase alfa) 300 mg administered every other week for 48 weeks and continued during the extension period1
    • 1 patient withdrew after week 1 due to inability to continue with study procedures1
    • Brineura-treated patients were compared to an independent natural history cohort that included 42 patients who satisfied inclusion criteria for the clinical study1

Learn more about the natural history of CLN2 disease at >

The clinical study was designed to assess disease progression using the CLN2 Clinical Rating Scale1,2

  • CLN2 Clinical Rating Scale has a Motor and a Language domain, each with a 0-to-3 score (the highest possible combined score is 6)1,2
    • Each score represents a range of function
    • Only the Motor domain was used to assess disease progression1
    • Due to the inability to establish comparability for the CLN2 Language domain ratings between the clinical study with extension and the natural history cohort, efficacy of Brineura for the Language domain cannot be established1
motor function
Adapted from: Steinfeld R, et al. Am J Med Genet. 2002:112:347-354.
*In some children, motor development was never completely normal and was rated 2.

Baseline demographics of enrolled population1,2

Baseline demographics of enrolled population

*Enrolled patient had a single dose and withdrew consent due to inability to comply with study procedures.1
‡Similar distribution to natural history control group.5
§Common alleles are c.622C>T and c.509-1G>C.6
SD, standard deviation.

  • Patients were evaluated for efficacy if they had a combined Motor plus Language CLN2 score of less than 6 at screening1
    • Two patients with a combined Motor plus Language score of 6 (grossly normal for both domains) were excluded from the efficacy analysis; they maintained that score throughout the study period1

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Brineura safety was evaluated in a clinical study of 24 patients with CLN2 disease

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Brineura Efficacy Results

Brineura efficacy was evaluated in 24 patients with CLN2 disease in a nonrandomized, single-arm clinical study with extension.


  1. Brineura [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2020.
  2. Data on file, BioMarin Pharmaceutical Inc.
  3. Schulz A, Ajayi T, Specchio N, de Los Reyes E, Gissen P, Ballon D, Dyke JP, Cahan H, Slasor P, Jacoby D, Kohlschütter A; CLN2 Study Group. Study of Intraventricular Cerliponase Alfa for CLN2 Disease. N Engl J Med. 2018 May 17;378(20):1898-1907. doi: 10.1056/NEJMoa1712649. Epub 2018 Apr 24. PMID: 29688815.
  4. 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.
  5. Nickel M, Jacoby D, Lezius S, et al. Natural history of CLN2 disease: quantitative assessment of disease characteristics and rate of progression. Poster session presented at: The 12th Annual WORLD Symposium; February – March 2016; San Diego, CA.
  6. Fietz M, AlSayed M, Burke D, et al. Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Expert recommendations for early detection and laboratory diagnosis. Mol Genet Metab. 2016;119:160-167.


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.

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.


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

Please see accompanying full Prescribing Information, or visit

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.