Subject:
Voretigene neparvovec-rzyl (Luxturna)
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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Inherited retinal dystrophies (IRD), also known as hereditary retinal diseases, broadly encompass numerous genetic retinal disorders that are associated with progressive visual dysfunction. They are caused by mutations in at least one of 220 different genes. More specifically, biallelic RPE65 mutation-associated retinal dystrophy affects approximately 1,000 to 2,000 people. Mutations in the RPE65 gene leads to reduced or absent levels of RPE65 activity, therefore blocking the visual cycle and resulting in impaired vision. Patients with biallelic RPE65 mutation-associated retinal dystrophy often experience night-time blindness due to early development of decreased light sensitivity and involuntary back-and-forth eye movements. As the disease progresses, patients may also experience loss in peripheral vision, development of tunnel vision, and eventually loss of central vision, which results in complete blindness.
In December 2017, FDA approved Luxturna (voretigene neparvovec-rzyl) for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. Luxturna is the first directly administered gene therapy that targets a disease caused by mutations in a specific gene. Luxturna received Orphan Drug designation and was granted Priority Review and Breakthrough Therapy designations. Luxturna works by using a naturally occurring adeno-associated virus as a vehicle to deliver normal human RPE65 gene directly to retinal cells to restore the patient’s vision.
Luxturna (voretigene neparvovec-rzyl) suspension for subretinal infusion is an adeno-associated virus vector-based gene therapy. Each dose of Luxturna is a customized treatment created using an individual patient’s own cells. By delivering a normal copy of the RPE65 gene directly to retinal cells, the patient can produce the normal protein that converts light to an electrical signal in the retina to restore vision loss in the patient. Therefore, patients must have viable retinal cells as determined by the treating physician.
The safety and efficacy of Luxturna in pediatric and adult patients with biallelic RPE65 mutation-associated retinal dystrophy was evaluated in an open-label, two-center, randomized trial. 21 subjects were randomized to receive subretinal injection of Luxturna and 10 patients were randomized to the control (non-intervention) group, whom were later crossed over to receive Luxturna after one year of observation. Bilateral subretinal injections of Luxturna were administered sequentially in two separate surgical procedures with an interval of 6 to 18 days. The efficacy of Luxturna was established on the basis of multi-luminance mobility testing (MLMT) score change from baseline after one year, which measured changes in functional vision. At one year, mean bilateral MLMT change score was 1.8 light levels for patients receiving Luxturna versus 0.2 in the control group (difference of 1.6, 95% CI 0·72–2·41, p=0·0013). 65% of patients receiving Luxturna passed MLMT at the lowest luminance level tested, demonstrating maximum possible improvement. The patients that received Luxturna demonstrated significant improvements in their ability to complete the obstacle course at low light levels as compared to the control group. The most common adverse reactions from treatment with Luxturna included conjunctival hyperemia, cataract, increased intraocular pressure and retinal tear.
Warning and precautions for Luxturna include: endophthalmitis, permanent decline in visual acuity, retinal abnormalities, increased intraocular pressure, expansion of intraocular air bubbles, and cataract.
Luxturna should be given only to patients who have viable retinal cells as determined by the treating physician(s). Treatment with Luxturna must be done separately in each eye on separate days, with at least six days between surgical procedures. It is administered via subretinal injection by a surgeon experienced in performing intraocular surgery. Patients should be treated with a short course of oral prednisone to limit the potential immune reaction to Luxturna.
Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
1. Luxturna (voretigene neparvovec-rzyl) is medically necessary based on the FDA approved indication for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy that meet ALL of the following:
· Member has confirmed inherited retinal dystrophy due to bilallelic RPE65 mutations; molecular diagnosis is to be performed, or confirmed, by a CLIA-approved laboratory. (documentation required)
· Member aged 12 months of age or older.
· Sufficient viable retinal cells as determined by non-invasive means, such as optical coherence tomography (OCT) and/or ophthalmoscopy. Member must have one of the following:
a) An area of retina within the posterior pole of >100 µm thickness shown on OCT, OR
b) ≥ 3 disc areas of retina without atrophy or pigmentary degeneration within the posterior pole, OR
c) Remaining visual field within 30 degrees of fixation as measured by a III4e isopter or equivalent.
· Member has not received gene therapy previously to the eye.
· No prior intraocular surgery within 6 months.
· Member does not have any pre-existing eye conditions or complicating systemic diseases that can alter ocular function, including all of the following:
a) Diabetes or sickle cell disease with any manifestation of advanced retinopathy (e.g. macular edema or proliferative changes).
b) Immunodeficiency (acquire or congenital) susceptible to opportunistic infection (e.g. CMV retinitis).
c) Any malignancies whose treatment could affect central nervous system function (e.g. radiation treatment of the orbit, leukemia with optic nerve or CNS involvement).
· Member is not pregnant and willing to use effective contraception for four months following administration.
· The prescriber is a specialist in the area of the patient’s diagnosis (e.g. retinal specialist) or has consulted with a specialist in the area of the patient’s diagnosis
[INFORMATIONAL NOTE: Based on the FDA approved prescribing information, treatment with Luxturna is not recommended for patients younger than 12 months of age because the retinal cells are still undergoing cell proliferation.]
2. When voretigene neparvovec-rzyl (Luxturna) is considered medically necessary, initial therapy will be approved once per lifetime based on the following FDA-approved labelling information:
a. One treatment course consists of systemic oral corticosteroid followed by subretinal injection of Luxturna.
b. Luxturna is administered as a subretinal injection as 1.5 x 1011 vector genomes (vg) in a total volume of 0.3 mL for each eye. The administration of Luxturna to each eye is to be performed on separate days within a close interval, but no fewer than 6 days apart.
c. Starting 3 days before administration of Luxturna, systemic oral corticosteroids equivalent to prednisone at 1 mg/kg/day (maximum of 40 mg/day) is to be administered for a total of 7 days and followed by tapering the dose during the following 10 days. The same corticosteroid dosing regimen applies for the administration of Luxturna to the second eye. If the corticosteroid taper following Luxturna administration to the first eye is not complete three days prior to the planned Luxturna administration to the second eye, then the corticosteroid regimen for the second eye replaces the taper for the first eye.
d. After administration of Luxturna, patient should be monitored for signs and symptoms of infection, macular abnormalities, intraocular pressure elevations and other warnings and precautions.
e. Luxturna will be approved for 60 days duration. A maximum of one treatment course per lifetime will apply.
3. All other uses of voretigene neparvovec-rzyl (Luxturna) are considered investigational.
Medicare Coverage
There is no National Coverage Determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a determination for this service. Therefore, Medicare Advantage Products 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:
Voretigene neparvovec-rzyl (Luxturna)
Luxturna (Voretigene neparvovec-rzyl)
References:
1. Luxturna™ [Package Insert]. Spark Therapeutics, Inc. Philadelphia, PA. December 2017.
2. Spark Therapeutics. FDA Briefing Document: BLA 125610: Voretigene Neparovec. October 12, 2017a. Available at: www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/bloodvaccinesandotherbiologics/ cellulartissueandgenetherapiesadvisorycommittee/ucm579290.pdf. Accessed December 2017.
3. FDA Press Release. FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss. Available at: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm589467.htm. Accessed December 2017.
4. Micromedex® Healthcare Series. n.d. Thomson Healthcare, Greenwood Village, CO. September 2017. http://www.thomsonhc.com.
5. National Institute of Health (NIH): U.S. National Library of Medicine. RPE65 gene. https://ghr.nlm.nih.gov/gene/ RPE65. Published June 25, 2017. Accessed December 2017.
6. Russell S. et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. The Lancet. Volume 390. August 26 2017. Available at: http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(17)31868-8.pdf. Accessed December 2017.
7. ClinicalTrials.gov. Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis. March 2017. Available at: https://clinicaltrials.gov/show/NCT00999609. Accessed December 2017.
8. Astuti G, Bertelsen M, Preising M, et al. Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark. Eur J Hum Genet. 2015;24(7):1071-1079.
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*
C9032
J3398
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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