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Horizon BCBSNJ
Uniform Medical Policy ManualSection:Drugs
Policy Number:151
Effective Date: 09/11/2020
Original Policy Date:05/23/2017
Last Review Date:09/08/2020
Date Published to Web: 05/30/2017
Subject:
Cerliponase Alfa (Brineura)

Description:
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IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.

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On April 27, 2017, the FDA approved Brineura (cerliponase alfa), an enzyme replacement therapy, indicated 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), also known as tripeptidyl peptidase (TPP1) deficiency.

CLN2 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), collectively referred to as Batten disease. CLN2 disease is a rare inherited disorder that primarily affects the nervous system. In the late infantile form of the disease, signs and symptoms typically begin between ages 2 and 4. The initial symptoms usually include language delay, recurrent seizures (epilepsy) and difficulty coordinating movements (ataxia). Affected children also develop muscle twitches (myoclonus) and vision loss. CLN2 disease affects essential motor skills, such as sitting and walking. Individuals with this condition often require the use of a wheelchair by late childhood and typically do not survive past their teens. Batten disease is relatively rare, occurring in an estimated two to four of every 100,000 live births in the United States. Brineura is the first drug FDA approved to treat CLN2. Continuing studies will test its use for children under two years of age and its long-term effects over 10 years.

The FDA approval of Brineura was based on a non-randomized single-arm dose escalation clinical study with extension in symptomatic pediatric patients with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease, confirmed by TPP1 deficiency. Brineura-treated patients were compared to untreated patients from a natural history cohort. The Motor domain of a CLN2 Clinical Rating Scale was used to assess disease progression. Scores ranged from 3 (grossly normal) to 0 (profoundly impaired) with unit decrements representing milestone events in the loss of motor function (ability to walk or crawl). Twenty-four patients, aged 3 to 8 years were enrolled in the Brineura single-arm clinical study. One patient withdrew after week 1 due to inability to continue with study procedures; 23 patients were treated with Brineura 300 mg every other week for 48 weeks, and continued treatment during the extension period.

In the clinical study with extension, patients were assessed for decline in the Motor domain of the CLN2 Clinical Rating Scale at 48, 72 and 96 weeks. Decline was defined as having an unreversed (sustained) 2-category decline or an unreversed score of 0 in the Motor domain of the CLN2 Clinical Rating Scale. Patients’ responses to Brineura treatment were evaluated if at screening a combined Motor plus Language CLN2 score of less than 6 was recorded. Two patients with a combined Motor plus Language CLN2 score of 6 were excluded from the analyses; they maintained that score throughout the study period. Motor scores of the 22 Brineura-treated patients in the clinical study with extension were compared to scores of the independent natural history cohort that included 42 untreated patients who satisfied inclusion criteria for the clinical study. The results of logistic modeling with covariates (screening age, screening motor score, genotype: 0 key mutations (yes/no)), demonstrated the odds of Brineura-treated patients not having a decline by 96 weeks were 13 times the odds of natural history cohort patients not having a decline [Odds Ratio (95% CI): 13.1 (1.2, 146.9)].

In an unadjusted non-randomized comparison, of the 22 patients treated with Brineura and evaluated for efficacy at week 96, 21 (95%) did not decline, and only the patient who terminated early was deemed to have a decline in the Motor domain of the CLN2 Clinical Rating Scale. Results from the natural history cohort demonstrated progressive decline in motor function; of the 42 patients in the natural history cohort 21 (50%) experienced an unreversed (sustained) 2-category decline or unreversed score of 0 in the Motor domain of the CLN2 Clinical Rating Scale over 96 weeks. To further assess efficacy, the 22 patients from the Brineura clinical study with a baseline combined Motor plus Language CLN2 score less than 6 were matched to 42 patients in the natural history cohort. Patients were matched based on the following covariates: baseline age at time of screening within 3 months, genotype (0, 1, or 2 key mutations), and baseline Motor domain CLN2 score at time of screening. Using the Motor domain of the CLN2 Clinical Rating Scale, decline was defined as having an unreversed 2-category decline or an unreversed score of 0. At 96 weeks, the matched analysis based on 17 pairs demonstrated fewer declines in the Motor domain for Brineura-treated patients compared to untreated patients in the natural history cohort.

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)

The requirements of the Horizon BCBSNJ Cerliponase Alfa (Brineura) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

1. Brineura (cerliponase alfa) is considered medically necessary for the treatment of late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) (or tripeptidyl peptidase (TPP1) deficiency) when all of the following criteria are met:

      a. Member has diagnosis of CLN2 disease confirmed by TPP1 deficiency (documentation of medical records required)
      b. Member is a pediatric patient 3 years of age or older
      c. Member has mild to moderate disease documented by a two domain score of 3-6 on motor and language domains of the Hamburg Scale, with a score of at least 1 in each of these two domains (documentation of medical records required)
      d. Member’s Motor domain of the CLN2 Clinical Rating Scale prior to starting therapy with Brineura (documentation of medical records required)
      e. Member’s seizures are stable (documentation of medical records required)
      f. Member does not have another inherited neurologic disease (e.g., other forms of CLN or seizures unrelated to CLN2), another neurological illness that may have caused cognitive decline (e.g., trauma, meningitis, hemorrhage), or contraindications to neurosurgery (e.g., congenital heart disease, severe respiratory impairment, or clotting abnormalities)
      g. Member does not require ventilation support (with the exception of noninvasive support at night)
      h. Member has not had generalized motor status epilepticus or severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks before the first dose is to be administered
      i. Member has not received stem cell, gene therapy, or enzyme replacement therapy in the past for CLN2
      j. Member does not have any of the following:
        • Signs or symptoms of acute or unresolved localized infection on or around the device insertion site (e.g. cellulitis or abscess);
        • Suspected or confirmed CNS infection (e.g. .cloudy CSF or positive CSD gram stain, or meningitis)
        • Acute intraventricular access device-related complication (e.g. leakage, extravasation of fluid, or device failure)
        • Ventriculoperitoneal shunts
      k. Brineura will be administered by, or under the direction of, a physician knowledgeable in intraventricular administration and aseptic technique must be strictly observed during preparation and administration.
    [INFORMATIONAL NOTE: In clinical study with extension, the Motor domain of a CLN2 Clinical Rating Scale was used to assess disease progression. Scores ranged from 3 (grossly normal) to 0 (profoundly impaired) with unit decrements representing milestone events in the loss of motor function (ability to walk or crawl).]

2. When Brineura (cerliponase alfa) is considered medically necessary, initial therapy will be approved for 6 months at the following FDA-approved dose:
      a. 300 mg administered once every other week by intraventricular infusion
    [INFORMATIONAL NOTE: 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 (Part Numbers: 82-1625, 82-1621, 82-1616) with the Codman® Ventricular Catheter (Part Number: 82-1650). 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.
    The essential performance requirements for this syringe pump used to deliver Brineura are as follows:
    - Delivery rate of 2.5 mL/hr with delivery accuracy of +/- 1 mL/hr
    - Compatible with 20 mL syringes provided in the Administration Kit for use with Brineura
    - Occlusion alarm setting to ≤ 281 mm Hg

    Administer Brineura and the Intraventricular Electrolytes using the provided Administration Kit for
    use with Brineura components. 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.

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

3. Continuation of Brineura (cerliponase alfa) will be approved every 6 months at the FDA-approved dose of 300 mg once every other week by intraventricular infusion when the member meets all of the following criteria:
      a. Continues to meet initial review criteria
      b. Member is able to tolerate intraventricular infusions showing no adverse reactions (i.e., hypersensitivity reactions meningitis and other intraventricular access device-related infections, cardiovascular adverse reactions, etc. ) (documentation of medical records required)
      c. There is evidence of efficacy and disease stability and/or improvement (i.e., no decline in the Motor domain of the CLN2 Clinical Rating Scale, defined as having a sustained 2-point decline or an unreversed score of 0 in the motor domain of the CLN2 Clinical Rating Scale) (documentation of medical records required)
      d. Members with cardiac abnormalities must have had a 12-lead ECG evaluation performed within the last 6 months
    [INFORMATIONAL NOTE: In the clinical study with extension, patients were assessed for decline in the motor domain of the CLN2 Clinical Rating Scale. The scale measures performance of mobility, with normal function being a score of 3 and no function being a score of 0. Decline was defined as having a sustained 2-point decline or an unreversed score of 0 in the motor domain of the CLN2 Clinical Rating Scale.

    In an unadjusted non-randomized comparison, of the 22 patients treated with Brineura and evaluated for efficacy at week 96, 21 (95%) did not decline, and only the patient who terminated early was deemed to have a decline in the Motor domain of the CLN2 Clinical Rating Scale.]

4. Brineura (cerliponase alfa) for the treatment of other conditions/diseases is considered investigational, including but not limited to Batten Disease, Jansky-Bielschowsky Disease.

Medicare Coverage:

There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL specifically for this drug. Therefore, Medicare Advantage will follow the Horizon BCBSNJ Medical Policy.

Medicaid Coverage:

For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Cerliponase Alfa (Brineura)
Brineura (Cerliponase Alfa)
Batten Disease, Cerliponase Alfa (Brineura) for

References:
1. Brineura™ (cerliponase alfa). [Prescribing Information]. BioMarin Pharmaceutical Inc. Novato, CA. December 2018.

    2. ClinicalTrials.gov. 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. Available from: https://clinicaltrials.gov/ct2/show/NCT01907087?term=NCT01907087&rank=1. Accessed April 29, 2017.

    3. U.S. Food and Drug Administration. FDA News Release: FDA approves first treatment for a form of Batten disease. [Online]. April 27, 2017. Available from: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm555613.htm

    4. ClinicalTrials.gov. A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 190 in Patients With CLN2 Disease. Available from: https://clinicaltrials.gov/ct2/show/NCT02485899?term=NCT02485899&rank=1. Accessed February 25, 2019.

    5. ClinicalTrials.gov. Brineura. Available at https://clinicaltrials.gov/ct2/results?cond=&term=brineura&cntry=&state=&city=&dist=. Accessed February 2019.
      Codes:
      (The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

      CPT*
      J0567

      HCPCS

      * CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

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      Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

      The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy

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