Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Cerliponase alfa (Brineura™)

Policy #:08.01.39b

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract

MEDICALLY NECESSARY

Cerliponase alfa (Brineura™) is considered medically necessary and, therefore, covered when all of the following criteria are met:
  • Diagnosis of late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease confirmed by either of the following:
    • TPP1 enzyme activity test indicating deficient activity in leukocytes or fibroblasts
    • TPP1 molecular test showing gene mutation on each parental allele of TPP1 gene
  • Individual is symptomatic (i.e., seizures, ataxia, language delay, vision loss)
  • Individual is 3 years of age and older

Continuation of cerliponase alfa (Brineura™) should take into consideration whether there was a confirmed response demonstrated by sustained ambulation and less than a 2-point decline in CLN2 motor domain score.

EXPERIMENTAL/ INVESTIGATIONAL

For all other uses, cerliponase alfa (Brineura™) is considered experimental/investigational and, therefore, not covered because its safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

BILLING REQUIREMENTS

If there is no specific HCPCS code available for the drug administered, the drug must be reported with the most appropriate unlisted code along with the corresponding National Drug Code (NDC).
Guidelines

The CLN2 Disease Clinical Rating Scale assesses disease progression in the following functional areas: motor, language, vision, and seizures. The motor and language domains were designated as primary endpoint of the Brineura studies. Each functional area is scored on a scale of 3 (normal function) to 0 (total loss of function), with the highest possible score being 6, with a decline of 1 point indicating a significant loss in function.

Motor Function
Language Function
3- Grossly normal gait; no prominent ataxia; no pathologic falls3- Apparently normal language; intelligible and
grossly age-appropriate; no decline noted yet
2- Independent gait, as defined by ability to walk without support for 10 steps; will have obvious instability, and may have intermittent falls2- Language has become recognizably
abnormal; some intelligible words; may form
short sentences to convey concepts,
requests, or needs; this score signifies a
decline from a previous level of ability (from
the individual maximum reached)
1- Requires assistance to walk, or can crawl
only
1- Hardly understandable; few intelligible words
0- Can no longer walk or crawl0- No intelligible words or vocalizations

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Cerliponase alfa (Brineura™) was approved by the FDA on April 27, 2017 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).

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, cerliponase alfa (Brineura) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

Description

Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is one of a group of inherited, neurodegenerative, lysosomal storage disorders collectively referred to as Batten disease. It is a rare autosomal recessive disease caused by a deficiency of tripeptidyl peptidase 1 (TPP1) enzyme, due to a mutation in the TPP1 gene. It is characterized by seizures, ataxia, language delays, blindness, and early death. Language delay and seizures are typically the initial symptoms and usually present between the ages of 2 and 4 years of age. Visual impairment may begin as early as 4 years, leading to blindness by age 7 to 10 years. Children generally succumb to the disease by the mid-teenage years.

The tripeptidyl peptidase 1 (TPP1) gene provides instructions for making tripeptidyl peptidase 1 enzyme, which is an inactive enzyme. This enzyme, found in the cells' lysosomes, breaks down peptides into amino acids. A deficiency of this enzyme decreases the breakdown of peptides and thereby causes peptide accumulation in the lysosomes. These accumulations cause cell damage and eventually cell death, particularly in the nerve cells. The progressive death of nerve cells in the brain leads to the signs and symptoms of CLN2 disease.

Cerliponase alfa (Brineura) was approved April 27, 2017 to slow the loss of ambulation in symptomatic individuals 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2). It is a proenzyme, taken up by target cells in the central nervous system (CNS), and translocated to the lysosomes where it is activated. The activated form then cleaves the proteins, preventing the accumulation of lysosomal storage materials.

Cerliponase alfa (Brineura) is administered to the cerebrospinal fluid by intraventricular infusion at a dose of 300 mg once every other week.

CLINICAL TRIALS

The efficacy of cerliponase alfa (Brineura) was studied over 96 weeks in a non-randomized, single-arm, dose-escalation study with extension consisting of 24 individuals, aged 3 to 8 years, with symptomatic late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), confirmed by TPP1 deficiency. Results of the Brineura-treated group were compared to the scores of untreated individuals from an independent natural history cohort, consisting of 42 individuals. The matched efficacy population consisted of 21 treated individuals matched to an untreated individual based on baseline age, genotype, and motor CLN2 score. Assessment for decline in the motor domain of the CLN2 Clinical Rating Scale was done at 48, 72, and 96 weeks. Decline was defined as having an unreversed 2-point decline or an unreversed score of 0 in the motor domain of the CLN2 Clinical Rating Scale. The results showed that when compared to the natural cohort group at 96 weeks, 21/21 (100%) of the matched Brineura-treated individuals had an absence of 2-point decline in motor language (ML) score compared with 9/21 (43%) of the untreated individuals. Also, the majority (95%) of the Brineura-treated individuals demonstrated sustained ambulation, as evidenced by less than a 2-point decline in the CLN2 motor domain score.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References


Brineura™ [Prescribing Information] Novato, CA. Biomarin, April 2017. Available at: http://brineura.com/downloads/Brineura_PI.pdf. Accessed June 7, 2017.

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.

Lexi-Drugs Compendium. Brineura™. 06/09/2017. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed June 15, 2017.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Brineura™. 06/05/2017. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed June 15, 2017.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Brineura™ (cerliponase alfa) drug label [FDA Web site]. 04/2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761052lbl.pdf. Accessed June 7, 2017.

Williams RE, Adams HR, Blohm M, et al. Management strategies for CLN2 disease. Pediatr Neurol. 2017; 69:102-112.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

E75.4 Neuronal ceroid lipofuscinosis


HCPCS Level II Code Number(s)

J0567 Injection, cerliponase alfa, 1 mg




Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

Revisions for 08.01.39b
01/01/2019This policy has been identified for the HCPCS code update, effective 01/01/2019.

The following HCPCS code has been added to this policy:
J0567 Injection, cerliponase alfa, 1 mg

The following HCPCS codes have been termed from this policy:
C9014 Injection, cerliponase alfa, 1 mg
J3590 Unclassified biologics


08.01.39a
06/06/2018This policy has been reissued in accordance with the Company's annual review process.
01/01/2018This policy has been identified for the HCPCS code update, effective 01/01/2018.

The following HCPCS code has been added to this policy:
C9014 Injection, cerliponase alfa, 1 mg


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 01/01/2019
Version Issued Date: 01/02/2019
Version Reissued Date: N/A

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