Notification

Cerliponase alfa (Brineura®)


Notification Issue Date: 03/05/2019

This version of the policy will become effective 06/03/2019.

This policy has been updated to communicate dosing and frequency requirements for Cerliponase alfa (Brineura®).



Medicare Advantage Policy

Title:Cerliponase alfa (Brineura®)
Policy #:MA08.089c

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


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. 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. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

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 Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

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

MEDICALLY NECESSARY

Cerliponase alfa (Brineura®) is considered medically necessary and, therefore, covered for individuals 3 years of age and older, when all of the following criteria are met, including dosing and frequency:
  • 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 indicating pathogenic gene mutation on each parental allele of TPP1 gene
  • Individual is symptomatic (i.e., seizures, ataxia, language delay, vision loss)
  • Dosing and frequency: 300 mg via intraventricular infusion once every other week

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.

DOSING AND FREQUENCY REQUIREMENTS

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this policy to ensure consistency with the most recently published recommendations for the use of cerliponase alfa (Brineura®). Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount ofcerliponase alfa (Brineura®) outside of the Dosing and Frequency Requirements listed in this policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the utilization management activities. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for cerliponase alfa (Brineura®).

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.

When coverage of cerliponase alfa (Brineura®) is requested outside of the Dosing and Frequency Requirements listed in this policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.

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).
Policy 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 Evidence of Coverage, cerliponase alfa (Brineura®) is covered under the medical benefits of the Company’s Medical Advantage products when the medical necessity criteria and dosing and frequency requirements 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, December 2018. Available at: http://brineura.com/downloads/Brineura_PI.pdf. Accessed January 15, 2019.

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®. 01/08/2019. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed January 15, 2019.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Brineura®. 12/19/2018. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed January 15, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Brineura® (cerliponase alfa) drug label [FDA Web site]. 12/2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761052lbl.pdf. Accessed January 15, 2019.

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 MA08.089c
06/03/2019This version of the policy will become effective 06/03/2019.

This policy has been updated to communicate dosing and frequency requirements for Cerliponase alfa (Brineura®).).

Revisions for MA08.089b
01/01/2019This policy has been identified for the HCPCS code update, effective 01/01/2019.

TThe 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

MA08.089a
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

Revisions for MA08.089
09/08/2017This version of the policy will become effective 09/08/2017.

This new policy has been developed to communicate the Company’s coverage criteria for cerliponase alfa (Brineura®).






Version Effective Date: 06/03/2019
Version Issued Date: 06/03/2019
Version Reissued Date: N/A