Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Enzyme Replacement Therapy for Mucopolysaccharidosis (e.g., Aldurazyme®, Elaprase™, Vimizim™, Naglazyme®, Mepsevii™, etc.)

Policy #:08.00.70d

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

Laronidase (Aldurazyme®) is considered medically necessary and, therefore, covered for use in individuals with:
  • Hurler and Hurler-Scheie forms of mucopolysaccharidosis I (MPS I)
  • Scheie form of MPS I with moderate-to-severe symptoms

Idursulfase (Elaprase™) is considered medically necessary and, therefore, covered for the treatment of MPS II (Hunter Syndrome), in individuals who are at least 16 months of age.

Elosulfase alfa (Vimizim) is medically necessary and, therefore, covered for individuals with Mucopolysaccharidosis Type IVA (MPS IVA), also called Morquio A syndrome, who are at least 5 years of age.

Galsulfase (Naglazyme®) is considered medically necessary and, therefore, covered for the treatment of mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome).

Vestronidase alfa-vjbk (Mepsevii) is considered medically necessary and, therefore, covered for the treatment of mucopolysaccharidosis VII (MPS VII, Sly Syndrome).

EXPERIMENTAL/INVESTIGATIONAL

All other uses of enzyme replacement therapy for mucopolysaccharidosis (e.g., Aldurazyme®, Elaprase™, Vimizim™, Naglazyme®, Mepsevii, etc.) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
Guidelines

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, enzyme replacement therapy for mucopolysaccharidosis (e.g., Aldurazyme®, Elaprase™, Vimizim™, Naglazyme®, Mepsevii, etc.) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

HOME INFUSION

Enzyme replacement therapy for mucopolysaccharidosis (e.g., Aldurazyme®, Elaprase™, Vimizim™, Naglazyme®, Mepsevii, etc.) may be available under the medical benefit for applicable lines of business through home infusion providers. Member’s benefit for home infusion should be verified.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Laronidase (Aldurazyme®) received initial US Food and Drug Administration (FDA) approval on April 30, 2003.

Idursulfase (Elaprase™) was approved by the FDA in July 2006 for individuals with Hunter syndrome (Mucopolysaccharidosis II).

Elosulfase alfa (Vimizim) was approved by the FDA in February 2014 for individuals with Mucopolysaccharidosis type IVA (Morquio A syndrome).

Galsulfase (Naglazyme®) was approved by the FDA in May 2005 for individuals with Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome).

Vestronidase alfa-vjbk (Mepsevii) was approved by the FDA in November 11, 2017 for individuals with mucopolysaccharidosis VII (Sly syndrome).

PEDIATRIC USE

The safety and effectiveness of idursulfase (Elaprase™) in individuals below 16 months of age have not been established.

The safety and effectiveness of elosulfase alfa (Vimizim) and Galsulfase (Naglazyme®) in individuals below 5 years of age have not been established.

Description

Mucopolysaccharidosis (MPS) is a group of rare, inherited lysosomal storage disorders that affect glycosaminoglycan (GAG) degradation by the mutation in a lysosomal enzyme essential to GAG breakdown. The mutation can lead to the absence of the enzyme or a mutated inactive enzyme. Glycosaminoglycans are polysaccharides that play important roles in many tissues such as lubricant in joint fluid and the ground substance or bone and cartilage. MPS is clinically characterized by abnormalities in multiple organ systems and reduced life expectancy. There are several types of MPS.

Type
Disorder Name(s)
GAG Storage Material
Deficient Enzyme
Replacement Drug
MPS I
Hurler, Hurler-Scheie, Scheie
Dermatan sulfate, Heparan sulfate
Alpha - L-iduronidase
Laronidase (Aldurazyme®)
MPS II
Hunter
Dermatan sulfate, Heparan sulfate
Iduronate-2-sulfatase
Idursulfase (Elaprase™)
MPS III A-D
Sanfilippo
Heparan sulfate
Heparan N-sulfatase
alpha-N-acetylglucosaminidase
acetyl-CoA; alpha-glucosaminide acetyltransferase
N-acetylglucosamine 6-sulfatase
MPS IV A,B
Morquio
Keratan sulfate, chondroitin sulfate
Keratan sulfate
Galactose 6-sulfatase
Beta-galactosidase
A- Elosulfase alfa (Vimizim)
MPS V
This is now known as Scheie Syndrome, a subtype of MPS I.
MPS VI
Maroteaux-Lamy
Dermatan sulfate, Chondroitin sulfate
Arylsulfatase B
Galsulfase (Naglazyme®)
MPS VII
Sly syndrome
Dermatan sulfate, Heparan sulfate, Chondroitin sulfate
Beta- glucuronidase
Vestronidase alfa-vjbk (Mepsevii)
MPS IX
Hyaluronan
Hyaluronidase
The failure of GAG degradation causes an accumulation of partially degraded GAG inside lysosomes, which leads to an elevation of GAG fragments in urine, blood, and cerebral spinal fluid and cell, tissue, and organ dysfunction. Replacement of the deficient enzyme with an exogenous enzyme is one option to treat individuals with MPS.

MPS I can be classified into three subtypes, Hurler (severe), Hurler-Scheie, or Scheie (mild) syndrome. Some common symptoms are joint stiffness, corneal clouding, and ear, nose, and throat infections. MPS I is an autosomal recessive disorder caused by a deficiency of alpha-L-iduronidase. This leads to an accumulation of dermatan sulfate and heparan sulfate. Laronidase (Aldurazyme®), a polymorphic variant of the human enzyme alpha-L-iduronidase, was approved by the US Food and Drug Administration (FDA), as an orphan drug (a drug used to treat, prevent, or diagnose a rare disease), for individuals with Hurler and Hurler-Scheie forms of MPS I and for those with the Scheie form who have moderate-to-severe symptoms. The risk and benefits of treating mildly affected patients with the Scheie form have not been established.

MPS II, also known as Hunter Syndrome, is an X-linked disorder caused by a deficiency of iduronate-2-sulfatase leading to the accumulation of heparin sulfate and dermatan sulfate. Some common symptoms are skeletal abnormalities, hepatosplenomegaly, and mental retardation. Early onset (one to two years) is associated with the severe form of MPS II. Idursulfase (Elaprase™) was approved by the FDA as an orphan drug for individuals with MPS II or Hunter Syndrome. Idursulfase (Elaprase™) is a purified form of human iduronate-2-sulfatase.

MPS III, also known as Sanfilippo syndrome, has subtypes A to D. Some common symptoms are progressive intellectual disability and loss of previously acquired skills. This type leads to an accumulation of heparan sulfate. It is primarily a brain disease making enzyme replacement therapy not an option for treatment because the exogenous enzyme is unable to cross the blood-brain barrier.

MPS IV, also known as Morquio syndrome, is a progressive disease with predominant skeletal manifestations, like skeletal abnormalities, loose joints, and underdevelopment of odontoid process. MPS IV has two forms, A and B. MPS IV A is due to galactosamine-6-sulfatase deficiency causing a buildup of keratan sulfate and chondroitin sulfate. MPS IVB is due to beta galactosidase deficiency causing a buildup of keratan sulfate. Of MPS IV, only MPS IV A can be treated with exogenous enzymes. The FDA approved elosulfase alfa (Vimizim), a purified human enzyme N-acetyl-galactosamine-6-sulfatase, as an orphan drug for MPS IVA.

MPS V is now known as Scheie syndrome, a subtype of MPS I.

MPS VI, also known as Maroteaux-Lamy syndrome, is an autosomal recessive disorder caused by a mutation in arylsulfatase B leading to an accumulation of dermatan sulfate and chondroitin 4-sulfate. Galsulfase (Naglazyme®), purified human enzyme galsulfase, was approved by the FDA in May 2005 to improve walking and stair-climbing capacity in individuals with MPS VI.

MPS VII, also known as Sly syndrome, is an autosomal recessive disorder caused by a mutation in beta-glucuronidase leading to an accumulation of heparan sulfate, dermatan sulfate, chondroitin-4-sulfate, and chondroitin-6-sulfate. Vestronidase alfa-vjbk (Mepsevii) is a recombinant human lysosomal beta glucuronidase that was approved by the FDA for the treatment of MPS VII or Sly Syndrome. The effect of vestronidase alfa-vjbk (Mepsevii) has not been determined in central nervous system manifestations of MPS VII.

MPS VIII is no longer recognized.

MPS IX is a rare disorder resulting from a deficiency of hyaluronidase leading to an accumulation of hyaluronan. Currently there is no FDA- approved enzyme replacement therapy for hyaluronidase deficiency.

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References


Aldurazyme® (laronidase) [prescribing information]. Cambridge, MA. Sanofi/Genzyme Corporation; April 2013. Available at: http://www.aldurazyme.com/pdf/az_us_hc_pi.pdfAccessed January 16, 2018.

BioMarin Pharmaceutical Inc. galsulfase (Naglazyme®). About MPS VI. Novato, CA; 2013. Available at: http://www.naglazyme.com/. Accessed January 16, 2018.

Elaprase™ (idursulfase) [prescribing information]. Cambridge, MA: Shire Human Genetic Therapies, Inc.; 06/2013. Available at: http://elaprase.com/. Accessed January 16, 2018.

Elsevier Gold's Standard Clinical Pharmacology Compendium. Elosulfase alfa. [Clinical Key Web site]. 09/13/2016. Available at: https://www.clinicalkey.com/#!/content/drug_monograph/6-s2.0-3840. [via subscription only]. Accessed January 16, 2018.

Elsevier Gold's Standard Clinical Pharmacology Compendium. Galsulfase.[Clinical Key Web site]. 08/01/2017. Available at: https://www.clinicalkey.com/#!/content/drug_monograph/6-s2.0-3436. [via subscription only]. Accessed January 22, 2018.

Elsevier Gold's Standard Clinical Pharmacology Compendium. Idursulfase. [Clinical Key Web site]. 07/26/2017. Available at: https://www.clinicalkey.com/#!/content/drug_monograph/6-s2.0-3526. [via subscription only]. Accessed January 22, 2018.

Elsevier Gold's Standard Clinical Pharmacology Compendium. Laronidase. [Clinical Key Web site]. 03/27/2017. Available at: https://www.clinicalkey.com/#!/content/drug_monograph/6-s2.0-2786. [via subscription only]. Accessed January 22, 2018.

Galsulfase. American Hospital Formulary Service (AHFS). Drug Information 2017. [Lexicomp Web site]. 03/16/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed January 22, 2018.

Harmatz PR. Genetics of Mucopolysaccharidosis Type VI Medication. Updated: 03/20/2017. Available at: http://emedicine.medscape.com/article/946474-overview. Accessed January 22, 2018.

Idursulfase. American Hospital Formulary Service (AHFS). Drug Information 2018. [Lexicomp Web site]. 3/08/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed January 23, 2018.

Laronidase. American Hospital Formulary Service (AHFS). Drug Information 2018. [Lexicomp Web site]. 3/08/2017. Available at: http://online.lexi.com/lco/action/home. [via subscription only]. Accessed January 23, 2018.

Lexi-Drugs Compendium. Elosulfase alfa. [Lexicomp Online Web site]. 12/04/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed January 23, 2018.

Lexi-Drugs Compendium. Galsulfase. [Lexicomp Online Web site]. 12/04/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed January 23, 2018.

Lexi-Drugs Compendium. Idursulfase. [Lexicomp Online Web site]. 12/04/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed January 23, 2018.

Lexi-Drugs Compendium. Laronidase. [Lexicomp Online Web site]. 12/22/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed January 23, 2018.

Lexi-Drugs Compendium. vestronidase alfa-vjbk. [Lexicomp Online Web site]. 11/16/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed January 23, 2018.

MedlinePlus. National Library of Medicine. Medical Encyclopedia. Hunter syndrome. [MedlinePlus Web site]. 12/21/2017. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/001203.htm. Accessed January 24, 2018.

MedlinePlus. National Library of Medicine. Medical Encyclopedia. Hurler syndrome. [MedlinePlus Web site]. 12/21/2017. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/001204.htm. Accessed January 24, 2018.

MedlinePlus. National Library of Medicine. Medical Encyclopedia. Sanfilippo syndrome. [MedlinePlus Web site]. 12/21/2017. Available at: https://www.nlm.nih.gov/medlineplus/ency/article/001210.htm. Accessed January 24, 2018.

Mepsevii™ (vestronidase alfa-vjbk) [prescribing information]. Novato, CA: Ultragenyx Pharmaceutical Inc.; 11/2017. Available at: http://www.mepsevii.com/. Accessed January 16, 2018.

National Library of Medicine. Genetics Home Reference: Your Guide to Understanding Genetic Conditions. Mucopolysaccharidosis type I. 1/23/2018. Available at: http://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-i. Accessed January 23, 2018.

National Library of Medicine. Mucopolysaccharidosis Type II. Genetics Home Reference: Your Guide to Understanding Genetic Conditions. 01/23/2018. Available at http://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-ii. Accessed January 23, 2018.

National Library of Medicine. Mucopolysaccharidosis Type III. Genetics Home Reference: Your Guide to Understanding Genetic Conditions. 01/23/2018. Available at http://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iii. Accessed January 23, 2018.

National Library of Medicine. Mucopolysaccharidosis Type VI. Genetics Home Reference: Your Guide to Understanding Genetic Conditions. 01/23/2018. Available at http://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vi. Accessed January 23, 2018.

National Library of Medicine. Mucopolysaccharidosis Type VII. Genetics Home Reference: Your Guide to Understanding Genetic Conditions. 01/23/2018. Available at http://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vii. Accessed January 23, 2018.

National Organization for Rare Disorders (NORD). Morquio Syndrome. 2017. Available at:
http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/299/viewAbstract. Accessed January 23, 2018.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Elosulfase alfa. 03/18/2016. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed January 22, 2018.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Galsulfase. 08/25/2017. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed January 22, 2018.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Idursulfase. 11/27/2017. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed January 22, 2018.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Laronidase. 08/29/2017. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed January 22, 2018.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Vestronidase alfa-vjbk. 1/08/2018. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed January 16, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Galsulfase (Naglazyme®) Product approval information. 05/2005. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2005/125117_0000_ltr.pdf. Accessed January 23, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Idursulfase. Product approval information. [labeling]. [FDA Web site]. Approval 2006. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2006/125151s0000_Ltr.pdf
Accessed January 23, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Laronidase. Product approval information. [labeling]. [FDA Web site]. Approval 2003. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2003/larobio043003L.htm
Accessed January 23, 2018.

US Food and Drug Administration. FDA approved labeling for galsulfase (Naglazyme®) 3/2013. Available at:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125117s111lbl.pdf. Accessed January 23, 2018.

US Food and Drug Administration. FDA approved labeling for elosulfase alfa
(Vimizim). 2/2014. Available at:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125460s000lbl.pdf. Accessed January 23, 2018.

US Food and Drug Administration. Idursulfase. FDA supplemental approval letter. 2/14/2014. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/125460Orig1s000ltr.pdf. Accessed January 23, 2018.

US Food and Drug Administration. Product approval information for vestronidase alfa-vjbk (Mepsevii™). 11/2017. Available at:
https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/761047Orig1s000ltr.pdf. Accessed January 23, 2018.

Vestronidase alfa-vjbk. American Hospital Formulary Service (AHFS). Drug Information 2018. [Lexicomp Web site]. 1/08/2018. Available at: http://online.lexi.com/lco/action/home. [via subscription only]. Accessed January 23, 2018.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

E76.01 Hurler's syndrome

E76.02 Hurler-Scheie syndrome

E76.03 Scheie's syndrome

E76.1 Mucopolysaccharidosis, type II

E76.210 Morquio A mucopolysaccharidoses

E76.29 Other mucopolysaccharidoses



HCPCS Level II Code Number(s)

J1322 Injection, elosulfase alfa, 1 mg

J1458 Injection, galsulfase, 1 mg

J1743 Injection, idursulfase, 1 mg

J1931 Injection, laronidase, 0.1 mg

J3397 Injection, vestronidase alfa-vjbk, 1 mg



Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

Revisions to 08.00.70d
01/01/2019This policy has been identified for the HCPCS code update, effective 01/01/2019.

The following HCPCS code has been added to this policy:
J3397 Injection, vestronidase alfa-vjbk, 1 mg

The following HCPCS codes have been termed from this policy:
C9399 Unclassified drugs or biologicals
J3590 Unclassified biologics


Revisions to 08.00.70 08.00.70c
03/16/2018This policy has undergone a routine review and the medical necessity criteria have been revised to reflect the United States Food and Drug Administration (FDA) labeling and drug compendia (i.e., Micromedex, AHFS-DI, Lexicomp).


Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date: 01/01/2019
Version Issued Date: 01/03/2019
Version Reissued Date: N/A

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