Last Review Date: 09/05/2024

Date of Origin: 5/30/2017

Dates Reviewed: 05/2017, 04/2018, 02/2019, 02/2020, 02/2021, 02/2022, 02/2023, 02/2024, 09/2024

1. Length of Authorization

Coverage will be provided for 6 months and may be renewed.

2. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

• Brineura 150 mg/5 mL single dose vial: 2 vials every 14 days

2. Max Units (per dose and over time) [HCPCS Unit]:

• 300 billable units (1 kit containing 2 vials) every 14 days

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 37 weeks post-menstrual age (gestational age at birth plus post-natal age) and weighs at least 2.5 kg; AND

Universal Criteria ¹

• Patient must not have any acute intraventricular access device-related complications (e.g., leakage, extravasation of fluid, or device failure); AND
• Patient must not have ventriculoperitoneal shunts; AND
• Patient has no sign or symptom of acute, unresolved localized infection on or around the device insertion site (e.g., cellulitis or abscess); or a suspected or confirmed CNS infection (e.g., cloudy CSF, positive CSF gram stain, or meningitis); AND

Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2); tripeptidyl peptidase 1 (TPP1) deficiency † Ф ^1,2,6-7

• Patient must have a definitive diagnosis of late infantile CLN2 confirmed by deficiency of the lysosomal enzyme tripeptidyl peptidase-1 (TPP1) and/or molecular analysis indicating two (2) pathogenic variants/mutations in the TPP1/CLN2 gene on chromosome 11p15; AND
• Patient has mild to moderate disease documented by a two-domain score of 3 to 6 on the motor and language domains of the Hamburg CLN2 Clinical Rating Scale, with a score of at least 1 in each of these two domains; AND
• Patient is ambulatory; AND
• Patients with a history of bradycardia, conduction disorder, or with structural heart disease will have electrocardiogram (ECG) monitoring performed during each infusion

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

Coverage may be renewed based on the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Absence of unacceptable toxicity from the drug or complications from the device. Examples of unacceptable toxicity or complications include: meningitis and other intraventricular access device-related infections, intraventricular access device-related complications (e.g., device leakage, device failure extravasation of CSF fluid, or bulging of the scalp around or above the access device), severe hypersensitivity reactions including anaphylaxis, severe cardiovascular reactions, infusion-associated reactions (e.g., vomiting, seizure, rash, pyrexia, hypersensitivity, and anaphylactic reaction), etc.; AND
• Patient has had a 12-lead ECG evaluation performed within the last 6 months [Note: Patients with cardiac abnormalities (e.g., a history of bradycardia, conduction disorder, or with structural heart disease) require an ECG during each infusion]; AND
• Patient has responded to therapy compared to pretreatment baseline with stability/lack of decline in motor function/milestones on the Motor domain of the Hamburg CLN2 Clinical Rating Scale [Decline is defined as having an unreversed (sustained) 2-category decline or an unreversed score of 0].

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J0567 - Injection, cerliponase alfa, 1 mg; 1 billable unit = 1 mg

NDC:

• Brineura 150 mg/5 mL (30 mg/mL) solution, two single-dose vials per carton co-packaged with Intraventricular Electrolytes Injection 5 mL in a single-dose vial: 68135-0811-xx

7. References

1. Brineura [package insert]. Novato, CA; BioMarin Pharmaceutical Inc.; July 2024. Accessed August 2024.
2. Schulz A, Specchio N, Gissen P. Intracerebroventricular Cerliponase Alfa (BMN 190) in Children with CLN2 Disease: Interim Results from a Phase 1/2, Open-Label, Dose-Escalation Study. Neuropediatrics 2016; 47 - FV02-06. DOI: 10.1055/s-0036-1583718.
3. Cherukuri A, Cahan H, Van Tuyl A, et al. Immunogenicity to cerliponase alfa, an enzyme replacement therapy for patients with CLN2 disease: results from a phase 1/2 study. Molecular Genetics and Metabolism. 2017 Jan 1;120(1):S35.
4. Schulz A, Specchio N, Gissen P, et al. Long-term safety and efficacy of intracerebroventricular enzyme replacement therapy with cerliponase alfa in children with CLN2 disease: interim results from an ongoing multicenter, multinational extension study. Molecular Genetics and Metabolism. 2017 Jan 1;120(1):S120.
5. Online Mendelian Inheritance in Man, OMIM^®. Johns Hopkins University, Baltimore, MD. MIM Number: 204500: 9/18/2016. World Wide Web URL: https://omim.org/
6. Schulz A, Ajayi T, Specchio N, et al. 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.
7. 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 Sep;119(1-2):160-7. doi: 10.1016/j.ymgme.2016.07.011.
8. Mole SE, Schulz A, Badoe E, et al. Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients. Orphanet J Rare Dis. 2021 Apr 21;16(1):185. doi: 10.1186/s13023-021-01813-5.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A