Medical Policy: 05.01.36
Original Effective Date: December 2017
Reviewed: April 2021
Revised: April 2021
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 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.
For information on enzyme replacement for Gaucher disease please see pharmacy policy Gaucher Disease Agents 05.02.42
Lysosomal storage diseases are a group of approximately 50 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomal storage diseases result when the lysosome – a specific organelle in the body's cells – malfunctions.
Lysosomal storage disorders are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the metabolism of lipids, glycoproteins (sugar containing proteins) or so-called mucopolysaccharides. Lysosomal storage diseases are characterized by an abnormal build-up of various toxic materials in the body's cells as a result of enzyme deficiencies. The diseases may affect different parts of the body, including the skeleton, brain, skin, heart, and central nervous system.
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 stabilize 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 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 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.
(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 |
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 |
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:
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.
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 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.
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 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.
Patients with Molybdenum Cofactor Deficiency Type A experience severe and rapidly progressive neurologic damage including intractable seizures, feeding difficulties and muscle weakness from the accumulation of toxic sulfite metabolites in the central nervous system. Most patients die in early childhood from infections. Before today’s approval, the only treatment options included supportive care and therapies directed towards the complications arising from the disease.
Patients with Molybdenum Cofactor Deficiency Type A cannot produce a substance known as cyclic pyranopterin monophosphate (cPMP). Nulibry is an intravenous medication that replaces the missing cPMP.
Not applicable
For information on enzyme replacement for Gaucher disease see pharmacy policy Gaucher Disease Agents 05.02.42
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.
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.
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.).
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.
Use of agalsidase beta in combination with migalastat (Galafold) is considered investigational.
Dosing is in accordance with the United States Food and Drug Administration approved labeling by one of the following:
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.).
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 of Lumizyme 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.).
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.
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.
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.
Dosing must be in accordance with the United States Food and Drug Administration approved labeling:
The use is considered medically necessary for a documented diagnosis of Molybdenum Cofactor Deficiency Type A
Dosing must be in accordance with the United States Food and Drug Administration. Nulibry is administered as a daily IV infusion. Recommended Dosage in Patients One Year of Age or Older: 0.9 mg/kg given as an intravenous infusion once daily.
All other uses for intravenous enzyme replacements above are considered not medically necessary.
Intrathecal Enzyme Replacement Therapy (ERT) is considered investigational.
To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes and / or diagnosis codes.
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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