68135-0811-XX Brineura 2 X 150 MG/5ML KIT (BIOMARIN PHARMACEUTICALS)
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.
Cerliponase alfa for the treatment of late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Cerliponase alfa for the treatment of other conditions/diseases is considered investigational.
Cerliponase alfa is considered medically appropriate if ALL of the following:
Individual is 3 years of age or older
Individual has 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
Individual has 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
Individual is ambulatory
Individual must not have ventriculoperitoneal shunts
Individual must not have acute intraventricular access device-related complications (e.g., leakage, device failure, or device-related infection, such as cellulitis, abscess or suspected or confirmed CNS infection)
Individual with history of bradycardia, conduction disorder, or with structural heart disease must have electrocardiogram (ECG) monitoring performed during infusion
Cerliponase alfa is considered medically appropriate for renewal if ALL of the following criteria are met
Individual continues to meet ALL of the initial approval criteria
Absence of unacceptable toxicity from the drug or complications from the device, e.g., meningitis and other intraventricular access device-related infections, intraventricular access device-related complications, severe hypersensitivity reaction, severe cardiovascular reactions, severe hypotension, etc.
Individual has a 12-lead ECG evaluation performed within the last 6 months (those with cardiac abnormalities require ECG during each infusion)
Individual 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)
|INDICATION(S)||DOSAGE & ADMINISTRATION|
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.
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.
LENGTH OF AUTHORIZATION
Coverage will be provided 6 months and may be renewed
Refer to DOSAGE LIMITS below
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.
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.
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).
Lexicomp Online. (2018). AHFS DI. Cerliponase alfa. Retrieved September 19, 2018 from Lexicomp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Evaluations. (2018, December). Cerliponase alfa. Retrieved February 11, 2019 from MICROMEDEX Healthcare Series.
U. S. Food and Drug Administration. (2018, December). Center for Drug Evaluation and Research. Brineura® (cerliponase alfa) injection, for intraventricular use. Retrieved February 11, 2019 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761052s003lbl.pdf.
ORIGINAL EFFECTIVE DATE: 7/28/2017
MOST RECENT REVIEW DATE: 4/9/2019
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.
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MaxMaximum billable units per dose and over time by indication as a Medical Benefit; 1 billable unit = 1 mg