BlueCross BlueShield of Tennessee Medical Policy Manual

Cerliponase Alfa

NDC CODE(S)

68135-0811-XX Brineura 150 MG/5ML SOLN (BIOMARIN PHARMACEUTICALS)

DESCRIPTION

Cerliponase alfa is a purified human enzyme produced by recombinant DNA technology.  The active substance is a recombinant human tripeptidyl peptidase-1 (rhTPP1), a lysosomal exopeptidase. Cerliponase alfa contains 544 amino acids with 5 consensus N-glycosylation sites on rhTPP1 that contain high mannose, phosphorylated high mannose and complex glycosylation structures.

CLN2 disease is a neurodegenerative disease caused by deficiency of the lysosomal enzyme tripeptidyl peptidase-1 (TPP1), which catabolizes polypeptides in the central nervous system (CNS).  Deficiency in TPP1 activity results in the accumulation of lysosomal storage materials normally metabolized by this enzyme in the CNS, leading to progressive decline in motor function.

Cerliponase alfa (rhTTP1), a proenzyme, is taken up by target cells in the CNS and is translocated to the lysosomes. Cerliponase alfa is activated in the lysosome and the activated proteolytic form of rhTPP1 cleaves tripeptides from the N-terminus of proteins.

REFER TO DECISION SUPPORT TREE

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL

RENEWAL CRITERIA

INDICATION(S) DOSAGE & ADMINISTRATION
CLN2 disease

300 mg administered once every other week by intraventricular infusion. Administer Brineura first followed by infusion of the Intraventricular Electrolytes each at an infusion rate of 2.5 mL/hr. The complete Brineura infusion, including the required infusion of Intraventricular Electrolytes, is approximately 4.5 hours.

  • 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 into the cerebrospinal fluid (CSF) by infusion via a surgically implanted reservoir and catheter (intraventricular access device). Brineura is intended to be administered via the Codman® HOLTER RICKHAM Reservoirs with the Codman® Ventricular Catheter. The intraventricular access device must be implanted prior to the first infusion. It is recommended that the first dose be administered at least 5 to 7 days after device implantation

  • Brineura is intended to be administered with the B Braun Perfusor® Space Infusion Pump System

  • Pre-treatment of patients with antihistamines with or without antipyretics or corticosteroids is recommended 30 to 60 minutes prior to the start of infusion.

Store upright in freezer (-25°C to -15°C); thaw at room temperature for ~60 minutes prior to administration

Hamburg CLN2 Clinical Rating Scale*

Motor Function Language Function
3 - Normal – Grossly normal gait, no prominent ataxia, no pathologic falls. 3 – Normal – Apparently normal language, intelligible and grossly age-appropriate, no decline noted yet.
2 - Clumsy, falls – Independent gait, as defined by ability to walk without support for 10 steps.  Will have obvious instability and may have intermittent falls. 2 - Abnormal – Language has become recognizably abnormal with some intelligible words.  May form short sentences to convey concepts, requests or needs.
1 - No unaided walking – Requires assistance to walk or can crawl only. 1 – Minimal – Hardly understandable with few intelligible words.
0 – Immobile – Can no longer walk or crawl. 0 - Unintelligible – No intelligible words or vocalizations.

*Retrieved from http://www.cln2connection.com/overview/natural-history/: The highest possible score when assessing motor and language function is 6.

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION  

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

SOURCE

U. S. Food and Drug Administration. (2017, April). Center for Drug Evaluation and Research. Brineura™ (cerliponase alfa) injection, for intraventricular use.  Retrieved July 12, 2017 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761052lbl.pdf.

ORIGINAL EFFECTIVE DATE:  7/28/2017

MOST RECENT REVIEW DATE:  7/28/2017

ID_MRxEx

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

Pharmaceutical Decision Support Tree

Cerliponase Alfa (Brineura)

  1. Is this the initial request for the agent?

If yes, go to question #2

If no, go to question #9

  1. Is the individual 3 years of age or older with a definitive diagnosis of late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency, confirmed by deficiency of the liposomal enzyme tripeptidyl peptidase-1 (TPP1) and/or molecular analysis indicating dysfunctional mutation of the TPP1 gene on chromosome 11p15?

If yes, go to question #3

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the individual ambulatory with mild to moderate disease documented by a two-domain score of 3 - 6 on motor and language domains of the Hamburg CLN2 Clinical Rating Scale, with a score of at least 1 in each of these two domains?

If yes, go to question #4

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Does the individual have ventriculoperitoneal shunts?

If yes, this does not meet medical necessity and/or medical appropriateness criteria

If no, go to question #5

  1. Is the individual free from acute intraventricular access device-related complications (e.g., leakage, device failure, or device-related infection)?

If yes, go to question #6

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Does the individual have a history of bradycardia, conduction disorder, or structural heart disease?

If yes, go to question #7

If no, go to question #8

  1. Does the individual have an order/agreement for electrocardiogram (ECG) monitoring to be performed during infusion?

If yes, go to question #8

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the requested dosage 300mg (1 kit/2 vials) every 14 days for a period of 6 months with possible renewal per the following?

300 mg administered once every other week by intraventricular infusion. Administer Brineura first followed by infusion of the Intraventricular Electrolytes each at an infusion rate of 2.5 mL/hr. The complete Brineura infusion, including the required infusion of Intraventricular Electrolytes, is approximately 4.5 hours.

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Does the individual continue to meet the initial criteria requirements in questions 2 through 8?

If yes, go to question #10

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is there absence of unacceptable toxicity from the drug or complications from the device, e.g., intraventricular access device leakage or infection, severe hypersensitivity reaction, severe hypotension, etc.?

If yes, go to question #11

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Has the individual had a 12-lead ECG evaluation performed within the last 6 months (those with cardiac abnormalities require ECG during each infusion)?

If yes, go to question #12

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Has the individual 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)?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

This document has been classified as public information.