Medical Policy: 05.01.36 

Original Effective Date: December 2017 

Reviewed: December 2018 

Revised: December 2018 

 

Notice:

This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy 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 will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

For information on enzyme replacement for Gaucher disease please see pharmacy policy Gaucher Disease Agents 05.02.42 

 

Lysosomal Storage Diseases

Lysosomal storage diseases are inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body's cells as a result of enzyme deficiencies. There are nearly 50 of these disorders altogether, and they may affect different parts of the body, including the skeleton, brain, skin, heart, and central nervous system.

 

Fabry Disease

Fabry disease is an inherited disorder that results from the buildup of a particular type of fat, called globotriaosylceramide, in the body's cells. Beginning in childhood, this buildup causes signs and symptoms that affect many parts of the body. Characteristic features of Fabry disease include episodes of pain, particularly in the hands and feet (acroparesthesias); clusters of small, dark red spots on the skin called angiokeratomas; a decreased ability to sweat (hypohidrosis); cloudiness of the front part of the eye (corneal opacity); problems with the gastrointestinal system; ringing in the ears (tinnitus); and hearing loss. Fabry disease also involves potentially life-threatening complications such as progressive kidney damage, heart attack, and stroke. Some affected individuals have milder forms of the disorder that appear later in life and affect only the heart or kidneys.

 

Current UK guidelines for the management of Fabry disease state that, “No trial has yet addressed the appropriate starting time of treatment or the group of patients most likely to benefit from therapy. However this is a chronic, progressive disorder. The aim of treatment is to prevent progression and where disease is already manifest to try and reverse or stabilise the disease. It is anticipated that treatment will be most successful when started early in the course of the disease. Conversely treatment late in the course of the disease may have limited efficacy.”

 

Cystinosis

Cystinosis is a rare genetic condition causing cystine accumulation in lysosomes throughout the body. The early signs of this disorder typically involve the kidneys and the eyes. Excessive storage of the amino acid cystine in all cells of the body results in impaired kidney function, increased sensitivity to light, and marked growth retardation. There are infantile (the most common and most severe), juvenile, and adult forms, each with associated symptoms.

 

Pompe Disease

Pompe disease is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially muscles, impairs their ability to function normally.

 

Researchers have described three types of Pompe disease, which differ in severity and the age at which they appear. These types are known as classic infantile-onset, non-classic infantile-onset, and late-onset.

 

  1. The classic form of infantile-onset Pompe disease begins within a few months of birth. Infants with this disorder typically experience muscle weakness (myopathy), poor muscle tone (hypotonia), an enlarged liver (hepatomegaly), and heart defects. Affected infants may also fail to gain weight and grow at the expected rate (failure to thrive) and have breathing problems. If untreated, this form of Pompe disease leads to death from heart failure in the first year of life.
  2. The non-classic form of infantile-onset Pompe disease usually appears by age one. It is characterized by delayed motor skills and progressive muscle weakness. The heart may be abnormally large (cardiomegaly), but affected individuals usually do not experience heart failure. The muscle weakness in this disorder leads to serious breathing problems, and most children with non-classic infantile-onset Pompe disease live only into early childhood.
  3. The late-onset type of Pompe disease may not become apparent until later in childhood, adolescence, or adulthood. Late-onset Pompe disease is usually milder than the infantile-onset forms of this disorder and is less likely to involve the heart. Most individuals with late-onset Pompe disease experience progressive muscle weakness, especially in the legs and the trunk, including the muscles that control breathing. As the disorder progresses, breathing problems can lead to respiratory failure.

 

Mucopolysaccharidosis (MPS)

(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.

 

TypeDisorder Name(s)GAG Storage MaterialDeficient EnzymeReplacement 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
 No replacement drug
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  No disorder name Hyaluronan Hyaluronidase  No replacement drug
  • 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.

 

Mucopolysaccharidosis type I 

Individuals with inherited deficiency of L-iduronidase have the lysosomal storage disease mucopolysaccharidosis type I.  Treatment with laronidase reverses the metabolic and pathologic abnormalities outside the central nervous system.  Mucopolysaccharidosis type I is classified into three distinct subgroups:

  • Hurler's syndrome - most severe form, with neurologic, skeletal, and visceral involvement, including hepatosplenomegaly, cardiac disease, airway obstruction, mental retardation/development delay, corneal clouding, and severe skeletal abnormalities; death often occurs before the age of ten.
  • Hurler-Scheie syndrome - intermediate form characterized by slower progression of same types of complications, but with minimal-to-no mental retardation; death is usually later (e.g., 20s).
  • Scheie's syndrome - least severe with less extensive disease; some individuals may have a normal life span.

 

Hunter Syndrome (Mucopolysaccharidosis type II)

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a condition that affects many different parts of the body and occurs almost exclusively in males. It is a progressively debilitating disorder; however, the rate of progression varies among affected individuals.

 

At birth, individuals with MPS II do not display any features of the condition. Between ages two and four, they develop full lips, large rounded cheeks, a broad nose, and an enlarged tongue (macroglossia). The vocal cords also enlarge, which results in a deep, hoarse voice. Narrowing of the airway causes frequent upper respiratory infections and short pauses in breathing during sleep. As the disorder progresses, individuals need medical assistance to keep their airway open.

 

Many other organs and tissues are affected in MPS II. Individuals with this disorder often have a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), an enlarged liver and spleen (hepatosplenomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). People with MPS II usually have thick skin that is not very stretchy. Some affected individuals also have distinctive white skin growths that look like pebbles. Most people with this disorder develop hearing loss and have recurrent ear infections. Some individuals with MPS II develop problems with the light-sensitive tissue in the back of the eye (retina) and have reduced vision. Carpal tunnel syndrome commonly occurs in children with this disorder and is characterized by numbness, tingling, and weakness in the hand and fingers. Narrowing of the spinal canal (spinal stenosis) in the neck can compress and damage the spinal cord. The heart is also significantly affected by MPS II, and many individuals develop heart valve problems. Heart valve abnormalities can cause the heart to become enlarged (ventricular hypertrophy) and can eventually lead to heart failure.

 

Morquio A syndrome (Mucopolysaccharidosis IVA)

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.

 

Maroteaux-4 Lamy Syndrome (Mucopolysaccharidosis type VI)

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.

 

Sly syndrome (Mucopolysaccharidosis type VII)

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.

 

Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2)/Jansky-Bielschowsky disease

The neuronal ceroid-lipofuscinoses (NCLs)/Batten Disease are a group of inherited, neurodegenerative, lysosomal storage disorders characterized by progressive intellectual and motor deterioration, seizures, and early death There are 14 known forms of Batten disease and you will often hear them referred to as CLN1-CLN14. Clinical phenotypes have been characterized traditionally according to the age of onset and order of appearance of clinical features. CLN2 late infantile disease is sometimes called Jansky-Bielschowsky Disease or late infantile NCL (LINCL). Late infantile neuronal ceroid lipofuscinoses (LINCLs) are a genetically heterogeneous group of neuronal ceroid lipofuscinoses typically characterized by onset during infancy or early childhood with decline of mental and motor capacities, epilepsy, and vision loss through retinal degeneration.

 

Lysosomal acid lipase (LAL) deficiency

Lysosomal acid lipase deficiency is an inherited condition characterized by problems with the breakdown and use of fats and cholesterol in the body (lipid metabolism). In affected individuals, harmful amounts of fats (lipids) accumulate in cells and tissues throughout the body, which typically causes liver disease. There are two forms of the condition. The most severe and rarest form begins in infancy. The less severe form can begin from childhood to late adulthood.

       

      Prior Approval:

      Not applicable

       

      Policy:

      Aldurazyme (laronidase) (J1931)

      Dosing must be in accordance with the United States Food and Drug Administration approved labeling: Administered dose does not exceed 0.58 mg/kg intravenously once every week.

       

      The use is considered medically necessary for a documented diagnosis of Hurler and Hurler-Scheie forms of mucopolysacchararidoses I (MPS I).

       

      The use is considered medically necessary for a documented diagnosis of Scheie forms of mucopolysacchararidoses I (MPS I) with moderate to severe symptoms.

       

      Brineura (cerliponase alfa) (C9014)

      Dosing must be in accordance with the United States Food and Drug Administration approved labeling: Administered dose does not exceed 300 mg intravenously once two weeks.

       

      The use is considered medically necessary for a documented diagnosis of late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency and Jansky-Bielschowsky disease/Batten disease (CLN2), in members at least 3 years of age who are symptomatic. The member must be ambulatory as a condition of treatment.

       

      Elaprase (idursulfase) (J1743)

      Dosing must be in accordance with the United States Food and Drug Administration approved labeling: administered dose does not exceed 0.5 mg/kg intravenously once every week.

       

      The use is considered medically necessary for a documented diagnosis of Hunter syndrome (mucopolysaccharidosis II) (MPS II) in individuals at least 16 months of age, when symptoms are present (hepatosplenomegaly, skeletal deformities, dysostosis, neurocognitive decline, cardiovascular disorders, etc.).

       

      Fabrazyme (algalsidase beta) (J0180)

      Dosing must be in accordance with the United States Food and Drug Administration approved labeling: administered dose does not exceed 1 mg/kg intravenously every two weeks.

       

      The use is considered medically necessary for a documented diagnosis of Fabry disease in those 8 years of age and older.

       

      Kanuma (sebelipase alfa) (J2840)

      Dosing is in accordance with the United States Food and Drug Administration approved labeling by one of the following:

      • For rapidly progressive disease presenting within the first 6 months of life: administered initial starting dose is 1 mg/kg intravenously once weekly, up to a maximum of 3 mg/kg once weekly
      • Pediatric and adult patients with stabilized disease: administered dose does not exceed 1 mg/kg intravenously every other week

       

      The use is considered medically necessary for a documented diagnosis of lysosomal acid lipase (LAL) deficiency (Wolfman disease, cholesteryl ester storage disease [CESD]) when symptoms are present (e.g., abdominal distention, hepatosplenomegaly, liver fibrosis, ascities, etc.).

       

      Lumizyme (alglucosidase alfa) (J0220) and Myozyme (alglucosidase alfa) (J0221)

      Dosing is in accordance with the United States Food and Drug Administration approved labeling: administered dose does not exceed 20 mg/kg intravenously every two weeks.

       

      The use is considered medically necessary for a  documented diagnosis of Pompe disease in individuals at least 16 months of age, when symptoms are present (e.g., cardiac hypertrophy, respiratory distress, skeletal muscle weakness, etc.).

      Mepsevii (vestronidase alpha-vjbk) (J3590)

      Dosing is in accordance with the United States Food and Drug Administration approved labeling: administered dose does not exceed 4 mg/kg intravenously every two weeks.

       

      The use is considered medically necessary for a documented diagnosis of MPS VII (Sly syndrome) in individuals at least 5 months of age.

       

      Naglazyme (galsulfase) (J1458)

      Dosing is in accordance with the United States Food and Drug Administration approved labeling: administered dose does not exceed 1 mg/kg intravenously once a week.

       

      The use is considered medically necessary for a  documented diagnosis of mucopolysaccharidosis VI (MPS VI), Maroteaux-4 Lamy Syndrome.

       

      Vimizim (elosulfase alfa) (J1322)

      The use is considered medically necessary for a documented diagnosis of mucopolysaccharidosis IVA (Morquio A syndrome) in individuals at least 5 years of age.

       

      The use is considered not medically necessary for the treatment of Morquio B syndrome.

       

      All other uses for intravenous enzyme replacements above are considered not medically necessary.

       

      Intrathecal Enzyme Replacement Therapy (ERT) is considered investigational.

       

      Procedure Codes and Billing Guidelines:

      To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes and / or diagnosis codes.

      • S9357 Home infusion therapy, enzyme replacement intravenous therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits codes separately), per diem 
      • J1931  Injection, laronidase, 0.1 mg
      • J0180  Injection, algalsidase beta, 1 mg 
      • J1458  Injection, galsulfase, 1 mg
      • J0220  Injection, alglucosidase alfa, 10 mg
      • J0221  Injection, alglucosidase alfa, (lumizyme), 10 mg
      • J0567  Injection, cerliponase alfa, 1 mg
      • J1743  Injection, idursulfase, 1 mg
      • J1322  Injection, elosulfase alfa, 1 mg
      • J2840  Injection, sebelipase alfa, 1 mg
      • J3590 Injection, unclassified biologics (will be used for MEPSEVII)

       

      Selected References:

      • National Institutes of Health (NIH). Gaucher Disease: Current Issues in Diagnosis and Treatment. NIH Technology Assessment Conference Statement. Bethesda, MD: NIH; February 27- March 1, 1995.
      • Weinreb NJ, Charrow J, Andersson HC, et al. Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: A report from the Gaucher Registry. Am J Med. 2002;113(2):112-119.
      • Vellodi A, Bembi B, de Villemeur TB, et al. Management of neuronopathic Gaucher disease: A European Consensus. Neuronopathic Gaucher Disease Task Force of the European Working Group on Gaucher Disease. J Inherit Metab Dis. 2001;24:310-327.
      • Mehta A, Beck M, Elliott P, et al; Fabry Outcome Survey investigators. Enzyme replacement therapy with agalsidase alfa in patients with Fabry's disease: An analysis of registry data. Lancet. 2009;374(9706):1986-1996.
      • U.S. Food and Drug Administration (FDA). FDA expands approval of drug to treat Pompe disease to patients of all ages; removes risk mitigation strategy requirements. FDA News Release. Silver Spring, MD: FDA: August 1, 2014.
      • Vpriv (velaglucerase alfa) [package insert]. Shire Human Genetic Therapies, Inc. Cambridge (MA): Apr 2013.
      • Elelyso (taliglucerase alfa) [package insert]. Pfizer Laboratories Inc. New York (NY): May 2012.
      • Cerezyme (imiglucerase) [package insert]. Genzyme Corp. Cambridge (MA): December 2012.
      • Genzyme Corporation. Lumizyme (alglucosidase alfa), for injection, for intravenous use. Prescribing Information. Cambridge, MA: Genzyme; revised August 2014.
      • Parenti G, Moracci M, Fecarotta S, Andria G. Pharmacological chaperone therapy for lysosomal storage diseases. Future Med Chem. 2014;6(9):1031-1045.
      • Valayannopoulos V, Malinova V, Honzík T, et al. Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency. J Hepatol. 2014;61(5):1135-1142.
      • Pisani A, Bruzzese D, Sabbatini M, et al. Switch to agalsidase alfa after shortage of agalsidase beta in Fabry disease: A systematic review and meta-analysis of the literature. Genet Med. 2016 Sep 8 [Epub ahead of print].
      • BioMarin Pharmaceutical Inc. Vimizim (elosulfase alfa) injection, for intravenous use. Prescribing Information. V1/2014. Novato, CA: BioMarin; revised February 2014.U.S. Food and Drug Administration (FDA). FDA approves Vimizim to treat rare congenital enzyme disorder. FDA News. Silver Spring, MD: FDA; February 14, 2014.
      • Genetics Home Reference, Health Conditions. Retrieved on 12/4/2017.
      • Mauer M, Koop J. Clinical features and diagnosis of Fabry disease. In: UpToDate, Waltham, MA: Walters Kluwer Health; 2016.
      • Hendriksz CJ, Berger KI, Giugliani R, at al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet A. 2015; 167A(1):11-25.
      • Burton BK, Berger KI, Lewis GD, et al. Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: a randomized, double-blind, pilot study. Am J Med Genet A. 2015; 167A(10):2272-2281.
      • Pastores GM, Rosenbloom B, Weinreb N, et al. A multicenter open-label treatment protocol (HGT-GCB-058) of velaglucerase alfa enzyme replacement therapy in patients with Gaucher disease type 1: safety and tolerability. Genet Med. 2014 May;16(5):359-66.
      • Hughes DA, Gonzalez DE, Lukina EA, et al. Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long-term data from phase III clinical trials. Am J Hematol 90:584–591, 2015.
      • Kronn DF, Day-Salvatore D, Hwu WL, et al. Management of Confirmed Newborn-Screened Patients With Pompe Disease Across the Disease Spectrum. Pediatrics 2017; 140:S24.
      • Hendriksz, C. J., Harmatz, P., Giugliani, R., Roberts, J., & Arul, G. S. (2018). Risks of long-term port use in enzyme replacement therapy for lysosomal storage disorders. Molecular genetics and metabolism reports, 15, 71-73. doi:10.1016/j.ymgmr.2018.02.007
      • Mistry, Pramod K. et al "Long-Term Effects of Oral Eliglustat on Skeletal Manifestations of Gaucher Disease Type 1: Results from Four Completed Clinical Trials." Blood 132.Suppl 1 (2018): 2396. Web. 27 Nov. 2018
      • Giugliani R, Lampe C, Guffon N, et al. Natural history and galsulfase treatment in mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome)--10-year follow-up of patients who previously participated in an MPS VI Survey Study. Am J Med Genet A 2014; 164A:1953
      • Wilson DP, Friedman M, Marulkar S, Hamby T, Bruckert E. Sebelipase alfa improves atherogenic biomarkers in adults and children with lysosomal acid lipase deficiency. J Clin Lipidol. 2018 May - Jun;12(3):604-614. doi: 10.1016/j.jacl.2018.02.020. Epub 2018 Mar 9
      • Cohen-Pfeffer JL, Gururangan S, Lester T, et al. Intracerebroventricular delivery as a safe, long-term route of drug administration. Pediatr Neurol. 2017;67:23-35.
      • Brineura [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2017.
      • Mole SE, Williams RE. Neuronal Ceroid-Lipofuscinoses. 2001 Oct 10 [Updated 2013 Aug 1]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
      • Derrick-Roberts ALK, Jackson MR, Pyragius CE5, Byers S. Substrate deprivation therapy to reduce glycosaminoglycan synthesis improves aspects of neurological and skeletal pathology in MPS I mice. Diseases. 2017;5(1).
      • National Health Services. SOP for Anderson-Fabry disease.

       

      Policy History:

      • December 2018 - Annual Review, Policy Revised
      • January 2018 - Interim Review, Policy Revised
      • December 2017 - New Policy

      Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

       

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