Description

Brineura® (cerliponase alfa) is a recombinant human tripeptidyl peptidase‑1 (TPP1) enzyme replacement therapy indicated to slow the loss of ambulation in patients with neuronal ceroid lipofuscinosis type 2 (CLN2 disease)

Policy 

Brineura (cerliponase alfa) is considered MEDICALLY NECESSARY for the treatment of neuronal ceroid lipofuscinosis type 2 (CLN2) when ALL of the following criteria are met:

1. Diagnosis of CLN2 was confirmed by enzyme assay demonstrating a deficiency of tripeptidyl peptidase 1 (TPP1) enzyme activity or by genetic testing.
2. Brineura will be administered by, or under the direction of, a physician knowledgeable in intraventricular administration.
3. Patient does not have acute intraventricular access-related complications (e.g., leakage, device failure or device-related infections)
4. Patient does not have ventriculoperitoneal shunts
5. Prescribed by or in consultation with a neurologist with expertise in the diagnosis of CLN2/TTP1 deficiency.

Continuation 

1. Patient does not have acute intraventricular access-related complications (e.g., leakage, device failure or device-related infections) AND
2. Patient does not have ventriculoperitoneal shunts AND
3. Patient demonstrates clinical benefit as evidenced by stabilization or slowed progression of motor or language function relative to expected disease trajectory.

Dosage 

• Aseptic technique must be strictly observed during preparation and administration. Brineura should be administered by, or under the direction of, a physician knowledgeable in intraventricular administration. Brineura is administered to the cerebrospinal fluid (CSF) by infusion via a surgically implanted reservoir and catheter.  
• Pre-treatment of patients with antihistamines with or without antipyretics or corticosteroids is recommended 30 to 60 minutes prior to the start of infusion.
• The recommended dosage is 300 mg administered once every other week as an intraventricular infusion, followed by infusion of intraventricular electrolytes over approximately 4.5 hours.  
• Prior to each infusion, inspect the intraventricular access device for signs of leakage, failure, or infection, and obtain cerebrospinal fluid for evaluation when clinically indicated.
• For complete information on preparation, specific intraventricular access device for use, and administration, see the full prescribing information.

BOXED WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS

• Life‑threatening hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with cerliponase alfa. These reactions may occur during the infusion or following repeated administration.Brineura must be initiated and administered in a healthcare setting equipped to manage hypersensitivity reactions, including access to cardiopulmonary resuscitation equipment. Patients should be observed during and after infusions, and treatment should be discontinued immediately if a severe hypersensitivity reaction occurs.

Coding Section 

References 

1. Brineura™ (cerliponase alfa). [Prescribing Information]. BioMarin Pharmaceutical Inc. Novato, CA. April 2017.
2. ClinicalTrials.gov. 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. Available from: https://clinicaltrials.gov/ct2/show/NCT01907087?term=NCT01907087&rank=1. Accessed April 29, 2017.
3. U.S. Food and Drug Administration. FDA News Release: FDA approves first treatment for a form of Batten disease. [Online]. April 27, 2017. Available from: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm555613.htm
4. ClinicalTrials.gov. A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 190 in Patients With CLN2 Disease. Available from: https://clinicaltrials.gov/ct2/show/NCT02485899?term=NCT02485899&rank=1. Accessed April 29, 2017. 
5. Geraets RD, Koh SY, Hastings ML, et al. Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis. Orphanet J Rare Dis. 2016; 11:40.
6. Worgall S, Kekatpure MV, Heier L, et al. Neurological deterioration in late infantile neuronal ceroid lipofuscinosis. Neurology. 2007; 69(6):521-535.
7. BioMarin Pharmaceutical. A multicenter, multinational, extension study to evaluate the long-term efficacy and safety of BMN 190 in patients with CLN2 disease. NLM Identifier: NCT02485899. Last updated on October 28, 2016. Available at: https://clinicaltrials.gov/ct2/show/NCT02485899?term=cerliponase+alfa&rank=2 . Accessed on July 10, 2017.
8. BioMarin Pharmaceutical. 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. NLM Identifier: NCT01907087. Last updated on April 25, 2016. Available at: https://clinicaltrials.gov/ct2/show/NCT01907087?term=cerliponase+alfa&rank=1 . Accessed on July 10, 2017.
9. Brineura^™ [Product Information], San Rafael, CA. Biomarin, April 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761052lbl.pdf . Accessed on July 10, 2017.
10. Cerliponase alfa. In: DrugPoints System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated April 27, 2017. Available at: http://www.micromedexsolutions.com. Accessed on July 10, 2017.
11. National Institute of Neurological Disorders and Stroke. Batten disease fact sheet. 2011. Available at: http://www.ninds.nih.gov/disorders/batten/detail_batten.htm. Accessed on July 10, 2017. 
12. Boustany RM. Cerliponase alfa and neuronal ceroid lipofuscinosis type 2: long-term outcomes and lessons for future research. Lancet Neurol. 2024;23(1):5–7.
13. Schulz A, Schwering C, Wibbeler E, et al. Real‑world clinical outcomes of patients with CLN2 disease treated with cerliponase alfa. Front Neurol. 2025;16:1516026.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

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