Medical Policy

 

Subject: Cerliponase Alfa (Brineura™)
Document #: DRUG.00099 Publish Date:    12/27/2017
Status: Revised Last Review Date:    08/03/2017

Description/Scope

This document addresses the use of cerliponase alfa (Brineura, BioMarin® Pharmaceutical, Inc, San Rafael, CA), a recombinant human tripeptidyl peptidase 1 enzyme replacement therapy in the treatment of late infantile neuronal ceroid lipofuscinosis type 2.

Position Statement

Medically Necessary:

Cerliponase alfa is considered medically necessary for late infantile neuronal ceroid lipofuscinosis type 2 when both of the following are present:

Investigational and Not Medically Necessary:

Cerliponase alfa is considered investigational and not medically necessary for all other indications.

Rationale

Neuronal ceroid lipofuscinoses are a subset of lysosomal storage disorders that can arise from genetic mutations. These disorders can affect individuals ranging from infants to adults depending on which gene is mutated. To date there are approximately nine genes that have been linked to the varying forms of neuronal ceroid lipofuscinosis. Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is a form of Batten disease, a fatal inherited disorder of the nervous system. CLN2 results from a functional reduction in  an enzyme called tripeptidyl peptidase 1 which is an acid protease that degrades proteins. In the absence of tripeptidyl peptidase 1, the lysosomal storage materials that are normally metabolized by this enzyme accumulate in organs, particularly in the brain. The buildup of these storage materials in the brain can cause progressive neurodegeneration and loss of cognitive, motor and visual functions.

In 2013, the United States Food and Drug Administration (FDA) granted Orphan Drug designation for cerliponase alfa for the treatment of CLN2. In April 2017, the FDA approved cerliponase alfa for symptomatic individuals with CLN2. This approval is based on a phase 1/2 open-label dose-escalation clinical trial (NCT01907087) in which study investigators evaluated the safety and efficacy of cerliponase alfa in individuals with late infantile CLN2 disease. A total of 24 participants were included and efficacy measures (which included disease rating scale and magnetic resonance imaging) were compared to a natural history control of 42 participants. Study participants were children age 3 to 16 years of age, all had a diagnosis of CLN2 of mild to moderate disease documented by a two-domain score of 3-6 on motor and language domains of the Hamburg Scale. Disease progression was measured by the Motor domain of a CLN2 Clinical Rating Scale in which scores ranged from 3 (grossly normal) to 0 (profoundly impaired). Decline was defined as an unreversed (sustained) 2-category decline or an unreversed score of 0. A total of 24 participants were originally enrolled in the single-arm study. One participant withdrew after 1 week. The remaining 23 participants received cerliponase alfa every other week for 48 weeks and continued treatment during the extension period. During the study with extension, the participants were assessed for decline in the Motor domain of the CLN2 Clinical Rating Scale at 48, 72, and 96 weeks. Two participants with a combined Motor plus Language CLN2 score of 6 were excluded from the analyses while the participant who dropped out of the study early was analyzed as having a decline at the time of termination. At week 96, when compared to the natural cohort group, of the 22 participants treated with cerliponase alfa, 21 of the participants did not decline while 21 participants in the natural cohort group showed a sustained decline. The most common side effects during the trial were fever, electrocardiogram abnormalities, and decreased cerebrospinal fluid protein.

Background/Overview

According to the National Institute of Neurological Disorders and Stroke (2011), Batten disease is an inherited disease of the nervous system. It typically begins in childhood and is fatal. There are four main types of neuronal ceroid lipofuscinoses; congenital, infantile, late infantile and adult. The late infantile type begins between ages 2 and 4 years of age. Early signs typically include loss of muscle coordination and drug-resistant seizures. This form progresses rapidly and death usually occurs between 8 and 12 years of age. Batten disease and other forms of neuronal ceroid lipofuscinoses are rare, occurring in an estimated 2 to 4 in 100,000 live births annually.

Cerliponase alfa is an infusion administered into the cerebrospinal fluid by way of a surgically implanted reservoir and catheter (an intraventricular access device). Cerliponase alfa is contraindicated if there are intraventricular access device complications such as leakage, device failure, or device-related infection or if the individual has ventriculoperitoneal shunts in place.

The most common side effects include fever, electrocardiogram abnormalities, decrease or increase of cerebrospinal fluid protein, vomiting, seizures, hypersensitivity, hematoma, headache, irritability, pleocytosis, device-related infection, bradycardia, feeling jittery, and hypotension.

Definitions

Enzyme replacement therapy: A treatment provided, usually via intravenous or intraventricular infusion, to provide enzymes in an individual unable to make sufficient amounts of that enzyme on their own.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

HCPCS

 

C9014

Injection, cerliponase alfa, 1 mg [Brineura]

J3490

Unclassified drugs [when specified as cerliponase alfa (Brineura)]

 

 

ICD-10 Diagnosis

 

 

E75.4

Neuronal ceroid lipofuscinosis

 

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

References

Peer Reviewed Publications:

  1. Geraets RD, Koh SY, Hastings ML, et al. Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis. Orphanet J Rare Dis. 2016; 11:40.
  2. Worgall S, Kekatpure MV, Heier L, et al. Neurological deterioration in late infantile neuronal ceroid lipofuscinosis. Neurology. 2007; 69(6):521-535.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. 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.
  2. 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.
  3. 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.
  4. 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.
Websites for Additional Information
  1. 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.
Index

Brineura
Cerliponase alfa

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History
Status Date Action
  12/27/2017 The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Coding section with 01/01/2018 HCPCS changes; added C9014.
Revised 08/03/2017 Medical Policy & Technology Assessment Committee (MPTAC) review. Removed age requirement 
criterion from Clinical Indications section. Updated Definitions and References sections.
  06/28/2017 Rationale section updated.
New 05/04/2017 MPTAC review. Initial document development.
Preliminary Discussion 02/02/2017 MPTAC review. Pre-FDA approval review.