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This is a new policy published on 3/24/2020. It will be effective on 4/25/2020 or later.
  
Horizon BCBSNJ
Uniform Medical Policy ManualSection:Drugs
Policy Number:201
Effective Date: 04/25/2020
Original Policy Date:03/24/2020
Last Review Date:
Date Published to Web: 03/24/2020
Subject:
Teprotumumab-trbw (Tepezza)

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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Thyroid eye disease (TED), sometimes called Graves' ophthalmopathy or Graves’ Eye Disease, is an autoimmune disease in which the immune system causes inflammation and swelling and stimulates the production of muscle tissue and fat behind the eye. The overactive thyroid gland (hyperthyroidism) is usually caused by Graves' disease. Up to one-half of people with Graves’ disease develop thyroid eye disease. TED has a higher prevalence in women than men (16 per 100,000 vs. 3 per 100,000, respectively). Both men and women demonstrate a bimodal pattern of age of diagnosis (40-44 and 60-64 years in women; 45-49 and 65-69 years in men). The median age of diagnosis is 43 years for all patients, with a range from 8-88 years. Patients diagnosed over the age of 50 years have a worse prognosis overall. Risk factors for TED include age, gender, ethnicity, and family history. A positive family history of TED is noted in 61% of TED patients.

In some people, thyroid eye disease can occur with normal levels of thyroid hormones (euthyroid) or low levels of thyroid hormones (hypothyroidism). Thyroid eye disease may occur in patients who already know they have thyroid disease, or it may be the first sign of Graves’ disease. While TED often occurs in people living with hyperthyroidism or Graves’ disease, it is a distinct disease and treating hyperthyroidism may not resolve the eye symptoms and signs.

In the “active phase” of thyroid eye disease, the main symptoms include inflammation and increased amounts of the tissue, muscles, and fat behind the eye (in the bony eye socket) causing the eyeballs to bulge out. If the eye is pushed far enough forward, the eyelids may not close properly when blinking and sleeping. The front part of the eye, called the cornea, may become unprotected, dry and, damaged. Also, the enlargement of the tissues and muscles of the eye may prevent it from working well, which affects eye position and eye movements leading to double vision. In severe cases, the inflammation and enlargement of the tissues, muscles, and fat behind the eye compresses the optic nerve, the nerve that connects the eye to the brain, causing vision loss. Although this condition impacts relatively few individuals, thyroid eye disease can be incapacitating. For example, the troubling ocular symptoms can lead to the progressive inability of people with thyroid eye disease to perform important daily activities, such as driving or working.

Treatment of patients with TED includes: reversal of hyperthyroidism, if present, monitoring for and prompt treatment of hypothyroidism, occurring as a consequence of treating hyperthyroidism, cessation of smoking, if applicable, local measures to reduce ocular surface irritation, and treatment of inflammation and swelling in the periorbital tissues. Prior to Tepezza (teprotumumab-trbw), there were no FDA approved pharmacotherapies to treat TED. Patients with mild symptoms (proptosis <3 mm above upper limit of normal) and active TED are managed with local supportive measures (ex. ointments, artificial tears). It is also important to address modifiable risk factors, such as smoking cessation, correction of thyroid dysfunction and selenium supplementation for six months (if deficient). Nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase 2 (COX-2) inhibitors, may also be helpful in some with mild symptoms of eye irritation, although there are no clinical trials supporting their use. For moderate symptoms (≥ 3 mm above upper limit of normal) to severe active TED, oral or IV glucocorticoids are the mainstay treatment option. IV glucocorticoids may be initiated in patients with mild active TED if present with eye muscle involvement, risk of progression and impaired quality of life. If high-dose glucocorticoid therapy is contraindicated, cannot be tolerated (eg, steroid psychosis, poorly controlled diabetes), or is ineffective, options include other medical therapies, external orbital radiation, or orbital decompression surgery.

Rituximab and tocilizumab have been studied in the treatment of active TED, but show varying results. Rituximab may be used in patients with glucocorticoid-refractory, severe disease who wish to avoid decompression surgery or, rarely, as initial therapy if glucocorticoids are contraindicated or poorly tolerated (eg, steroid psychosis, poorly controlled diabetes). The selection of patients for rituximab therapy is important, and patients with severe, new-onset Graves' orbitopathy may be those who benefit most from this approach. Tocilizumab targets interleukin (IL)-6 and has been used in patients with rheumatoid arthritis and has been investigated for the treatment of patients with Graves' orbitopathy who are not improving with glucocorticoids. External radiation has been used more often in Europe than in the United States, possibly because of retinal side effects seen early in its introduction, as well as questionable long-term beneficial effects from this modality. Furthermore, the availability of alternative secondary therapeutics has made the approach less useful. It is still sometimes used in patients with moderate-to-severe eye disease in whom IV glucocorticoids are contraindicated, cannot be tolerated, or are ineffective.

On January 21, 2020, the FDA approved Tepezza (teprotumumab-trbw), the first drug for the treatment of adults with thyroid eye disease. The FDA granted this application Priority Review, in addition to Fast Track and Breakthrough Therapy designations. It also received an Orphan Drug designation. It is a targeted inhibitor of the insulin-like growth factor-1 receptor that is administered to patients once every 3 weeks for a total of 8 infusions.

Tepezza (teprotumumab-trbw) was approved based on the results of two studies (Study 1 and 2) consisting of a total of 170 patients with active thyroid eye disease who were randomized to either receive Tepezza (teprotumumab-trbw) or a placebo. Study 1 was a phase 2 trial (NCT01868997) and Study 2 was a phase 3 trial (NCT03298867) called OPTIC. Of the patients who were administered Tepezza (teprotumumab-trbw), 71% in Study 1 and 83% in Study 2 demonstrated a greater than 2 millimeter reduction in proptosis (eye protrusion) as compared to 20% and 10% of subjects who received placebo, respectively.

The most common adverse reactions observed in patients treated with Tepezza (teprotumumab-trbw) are muscle spasm, nausea, alopecia (hair loss), diarrhea, fatigue, hyperglycemia (high blood sugar), hearing loss, dry skin, dysgeusia (altered sense of taste) and headache. As per the FDA labeled package insert, Tepezza (teprotumumab-trbw) should not be used if pregnant, and women of child-bearing potential should have their pregnancy status verified prior to beginning treatment and should be counseled on pregnancy prevention during treatment and for 6 months following the last dose of Tepezza (teprotumumab-trbw).

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

1. Treatment with Tepezza (teprotumumab-trbw) is considered medically necessary for the treatment of Thyroid Eye Disease (TED) in adults when ALL of the following criteria are met:
    A. The prescriber is a specialist in the area of the patient’s diagnosis (e.g. endocrinologist, ophthalmologist) or has consulted with a specialist in the area of the patient’s diagnosis.

    B. Member has a clinical diagnosis of Graves' disease associated with active moderate to severe TED with documentation of one or more of the following:
        Lid retraction of ≥ 2mm
        Moderate or severe soft-tissue involvement
        Proptosis ≥ 3 mm above normal values for race and gender
        Periodic or constant diplopia

    C. Member has a clinical activity score (CAS) ≥ 4 (on the 7-point version of the scale) for the most severely affected eye.

      [INFORMATIONAL NOTE: TED is termed active when inflammation is present and is typically measured with the Clinical Activity Score (CAS) – a 7 or 10 point component scale which measures the presence or absence of inflammatory signs/symptoms. The 7 point scale comprises two pain scores (reported by patients) and five physician evaluations of inflammation (a CAS ≥3 is indicative of active TED). The elements of the score include: spontaneous orbital pain, gaze evoked orbital pain, eyelid swelling that is considered to be due to active (inflammatory phase) TED, eyelid erythema, conjunctival redness that is considered to be due to active TED, chemosis (edema of the conjunctiva), inflammation of caruncle (flesh body at medial angle of eye).
    7-point Clinical Activity Score used to assess TED
    Elements aScore
    Spontaneous orbital pain1
    Gaze evoked orbital pain1
    Eyelid swelling that is considered to be due to active (inflammatory phase) TED1
    Eyelid erythema1
    Conjunctival redness that is considered to be due to active TED1
    Chemosis (edema of the conjunctiva)1
    Inflammation of caruncle (flesh body at medial angle of eye)1
    a - 7-point scale (excluding the last 3 elements) is used when no previous assessment is available. TED is considered active when CAS ≥3]
      D. Documentation that onset of active TED symptoms are within 9 months prior to initiation

      E. Clinical labs (documentation required) show that member is euthyroid with baseline disease under control or with mild hypo- or hyperthyroidism defined as free thyroxine (FT4) and free triiodothyronine (FT3) levels <50% above or below the normal limits

      F. Member has not received previous surgical therapy or orbital radiation for TED and does not require immediate surgical ophthalmological intervention

      G. If member is diabetic, must have a well-controlled disease

      H. Member has not been on high dose (>1 gram methylprednisolone or equivalent) oral or IV (intravenous) steroid therapy in the past 4 weeks

      I. Member has not previously been treated with rituximab

      J. Member has had an inadequate response, or there is a contraindication or intolerance to glucocorticoid therapy (maximum cumulative dose < 1000mg methylprednisolone or equivalent) used for the indication of TED OR there is documentation indicating why the member would not be a candidate for glucocorticoid therapy

      [INFORMATIONAL NOTE: In the clinical trials for Tepezza, trial 1 included patients with no previous medical or surgical treatment, excluding local supportive measures and oral steroids if the maximum cumulative dose is less than 1000 mg methylprednisolone or equivalent with at least 6 weeks between last administration of oral steroids and randomization. Trial 2 excluded patients with any steroid use (intravenous [IV] or oral) with a cumulative dose equivalent to ≥ 1 g of methylprednisolone for the treatment of TED. Previous steroid use (IV or oral) with a cumulative dose of <1 g methylprednisolone or equivalent for the treatment of TED and previous use of steroid eye drops is allowed if the corticosteroid was discontinued at least 4 weeks prior to Screening.]


    2. When Tepezza (teprotumumab-trbw) is considered medically necessary, therapy will be approved for 8 infusions over 6 months at the following FDA-approved dose:
          • Initiate dosing with 10mg/kg for the first infusion followed by 20 mg/kg every 3 weeks for 7 additional infusions
      [INFORMATIONAL NOTE: As per the FDA labeled package insert dosing section - Administer the diluted solution intravenously over 90 minutes for the first two infusions. If well tolerated, the minimum time for subsequent infusions can be reduced to 60 minutes. If not well tolerated, the minimum time for subsequent infusions should remain at 90 minutes. Do not administer as an intravenous push or bolus. Tepezza should not be infused concomitantly with other agents.

      Tepezza may cause infusion reactions. Infusion reactions have been reported in approximately 4% of patients treated with Tepezza. Signs and symptoms of infusion-related reactions include transient increases in blood pressure, feeling hot, tachycardia, dyspnea, headache and muscular pain. Infusion reactions may occur during any of the infusions or within 1.5 hours after an infusion. Reported infusion reactions are usually mild or moderate in severity and can usually be successfully managed with corticosteroids and antihistamines. In patients who experience an infusion reaction, consideration should be given to pre-medicating with an antihistamine, antipyretic, corticosteroid and/or administering all subsequent infusions at a slower infusion rate.]
      3. Continuation of Tepezza (teprotumumab-trbw) beyond 8 infusions over 6 months is considered investigational.

      4. Tepezza (teprotumumab-trbw) is considered investigational for all other indications, including but not limited to diabetic macular edema, scleroderma.

      Medicare Coverage:

      There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.
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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:
      Teprotumumab-trbw (Tepezza)
      Tepezza (Teprotumumab-trbw)

      References:
      1. Tepezza [package insert]. Horizon Therapeutics. Lake Forest, IL. January 2020.

      2. FDA approves first treatment for thyroid eye disease. FDA. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-thyroid-eye-disease. January 21, 2020.

      3. Thyroid Eye Disease. Prevent Blindness. Available at: https://www.preventblindness.org/thyroid-eye-disease. Accessed February 4, 2020.

      4. Smith TJ, Kahaly GJ, Ezra DG. Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med. 2017 May 4;376(18):1748-1761.

      5. Douglas RS, Kahaly GH, Patel A. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med. 2020 Jan 23;382(4):341-352.

      6. Wang Y, Patel A, Douglas R. Thyroid Eye Disease: How A Novel therapy may change the treatment paradigm. Therapeutics and Clinical Risk management. 2019;15:1305-18.

      7. Strianese D. Update on Graves disease: advances in treatment of mild, moderate and severe thyroid eye disease. Current opinion in ophthalmology. 2017;28(5):505-13.

      8. Kotwal A, Stan M. Current and Future Treatments for Graves' Disease and Graves' Ophthalmopathy. Hormone and metabolic research. 2018;50(12):871-86.

      9. Marcocci C, Kahaly GJ, Krassas GE, et al. Selenium and the Course of Mild Graves' Orbitopathy. New England Journal of Medicine. 2011;364(20):1920-31.

      10. Stan MN, Garrity JA, Carranza Leon BG, Prabin T, Bradley EA, Bahn RS. Randomized controlled trial of rituximab in patients with Graves' orbitopathy. The Journal of clinical endocrinology and metabolism. 2015;100(2):432-41.

      11. Perez-Moreiras JV, Alvarez-Lopez A, Gomez EC. Treatment of active corticosteroid-resistant graves' orbitopathy. Ophthalmic plastic and reconstructive surgery. 2014;30(2):162-7.

      12. Perez-Moreiras JV, Gomez-Reino JJ, Maneiro JR, et al. Efficacy of tocilizumab in patients with moderate to severe corticosteroid resistant Graves orbitopathy: A randomized clinical trial. American journal of ophthalmology. 2018;195:181-90.

      13. Liaboe CA, Clark TJ, Carter K, et al. Thyroid Eye Disease: An Introductory Tutorial and Overview of Disease. EyeRounds.org. Available at: https://webeye.ophth.uiowa.edu/eyeforum/tutorials/thyroid-eye-disease/Thyroid-Eye-Disease.pdf. November 18, 2016.

      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*

      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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