Clinical UM Guideline



Subject: Galsulfase (Naglazyme®)
Guideline #:  CG-DRUG-56 Current Effective Date:    09/27/2017
Status: Revised Last Review Date:    08/03/2017

Description

This document addresses the clinical indications for galsulfase (Naglazyme, BioMarin Pharmaceutical Inc., Novato, CA), a hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme. Galsulfase is an enzyme replacement therapy approved by the United States Food and Drug Administration (FDA) for the treatment of Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome).

Note: Please see these documents for related topics:

Clinical Indications

Medically Necessary:

Enzyme replacement therapy with galsulfase is considered medically necessary for the treatment of an individual with Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome) when the following criteria are met:

Not Medically Necessary:

Enzyme replacement therapy with galsulfase is considered not medically necessary when the above criteria are not met and for all other indications.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS  
J1458 Injection, galsulfase, 1 mg [Naglazyme]
S9357 Home infusion therapy, enzyme replacement intravenous therapy, (e.g., Imiglucerase); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
   
ICD-10 Diagnosis  
E76.29 Other mucopolysaccharidoses (includes Maroteaux-Lamy syndrome)
   
Discussion/General Information

Mucopolysaccharidosis type VI (or Maroteaux-Lamy syndrome) is a rare genetic disorder caused by the deficiency of N–acetylgalactosamine 4-sulfatase (also referred to as arylsulfatase B). The sulfatase activity deficiency results in the accumulation of glycosaminoglycans throughout the body. The accumulation leads to cellular, tissue and organ dysfunction. Galsulfase works by providing an exogenous enzyme which will be taken up into lysosomes and increase the catabolism of glycosaminoglycans. Initially approved in 2005 by the FDA, galsulfase is indicated for individuals with Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome).

This autosomal recessive lysosomal storage disorder has clinical manifestations which include short stature, skeletal abnormalities, respiratory complications, cardiac disease, hearing loss, corneal clouding, spinal cord compression, and reduced physical endurance. Tissue and organs enlarge and can become inflamed or scarred. Infants usually appear normal at birth, but those with rapidly progressive disease start to show symptoms shortly after birth and are typically diagnosed between 2 and 4 years of age. Many do not live to adulthood. Diagnosis of Mucopolysaccharidosis VI should begin with leukocyte arylsulfatase B (ARSB) and arylsulfatase A (ARSA) enzyme activity. Currently there is no routine screening procedure to diagnose a newborn baby with Mucopolysaccharidosis type VI.

Mucopolysaccharides can be measured in urine and enzyme activity can be measured in blood. If the urine shows an increase in dermatan sulfate and the blood shows a decrease in the activity of arylsulfatase B enzyme this is usually consistent with a diagnosis of Mucopolysaccharidosis VI. Measuring the enzyme activity in a small piece of skin is useful to confirm the blood and urine results. Gene sequencing is typically performed to confirm biochemical and functional testing.

In a 2006 phase III trial, Harmatz and colleagues reported on the safety and efficacy of galsulfase in the treatment of Mucopolysaccharidosis type VI. A total of 39 participants were randomized to receive either galsulfase or placebo for 24 weeks. At the 24-week evaluation, the participants who received galsulfase were noted to walk 92 meters more than the placebo group in a 12-minute walk test and climbed 5.7 stairs per minute in the 3-minute stair climb and urinary glycosaminoglycans levels declined. After the first 24 weeks, the participants received galsulfase for an additional 24 weeks in an open-label extension period. During the second 24 weeks, continued improvement was noted.

In a 2014 phase IV, open-label two-dose level study, Harmatz and colleagues evaluated the safety and efficacy of two doses of galsulfase. Due to the rarity of Mucopolysaccharidosis VI, a total of 4 infants were included in the study and were randomized 1:1 to receive weekly IV infusions of either 1 mg or 2 mg/kg of galsulfase for at least 52 weeks. Weight and length remained within the age-expected norms while skeletal abnormalities continued to progress. Urinary glycosaminoglycans levels decreased and were maintained at the 52-week mark. Stabilization or improvement was noted in hearing, cardiac function, hepatosplenomegaly and facial dysmorphism, but corneal clouding progressed. One of the participants experienced pyrexia during and after the infusions. There were no significant abnormal lab values reported during the study.

In 2014, Giugliani and colleagues reported outcomes for 117 participants affected with Mucopolysaccharidosis VI who were treated with galsulfase for a mean duration of 6.8 years. For the participants who received enzyme replacement therapy, height was increased by 20.4 cm in the 4–7 year-old baseline age group and by 16.8 cm in the 8–12 year-old baseline age group. For the participants less than 13 years old, they demonstrated improvement in forced vital capacity (FVC) by 68% and forced expiratory volume in 1 second (FEV1) by 55%. Those with less than 200 μg/mg baseline urinary glycosaminoglycan levels increased FVC by 48%. For the participants greater than 13 years old they had increased FVC by 12.8% and maintained FEV1. Those with less than 200 μg/mg baseline urinary glycosaminoglycan levels increased FVC by 15%. In the participants who completed the 6-minute walk test, they demonstrated a mean increase of 65.7 (100.6) m. Overall, there was neither significant improvement nor worsening in cardiac outcomes. Observed mortality rate among those treated with enzyme replacement therapy was and 16.5% (17/103) and was 50% (7/14) in naïve participants (unadjusted hazard ratio, 0.24; 95% confidence interval [CI], 0.10 to 0.59). Long-term enzyme replacement therapy with galsulfase was noted to be associated with improvements in pulmonary functions and endurance, stabilized cardiac function and increased survival. An increase in pulmonary function is considered clinically significant as pulmonary function generally declines in all individuals, including those with Mucopolysaccharidosis disorders (Lin, 2014).

In a 2016 case series by Lin and colleagues, the authors reported on nine participants with MPS VI who had either, or were currently receiving galsulfase. The duration of therapy ranged from 6.2 to 11.2 years. Biochemical and clinical responses were assessed during each year of treatment. During the treatment period there was a 69% decrease in urinary excretion of GAG. All participants had an improvement in shoulder range of motion. The 6-minute walk test was improved in 6 participants and the 3-minute stair climb increase was improved in 3 participants. Four of the participants underwent pulmonary function tests and all four had improved FEV1 and FVC. Liver and spleen size decreased or remained unchanged in all participants. None of the nine participants had appreciable growth affected by enzyme replacement therapy. Adverse effects included skin itching, shortness of breath, and fever, however the use of oral antihistamines, steroids and antipyretics allowed the participants to tolerate the enzyme replacement therapy. While this study does have limitations including its retrospective nature and lack of a control group, the long-term administration of galsulfase improved endurance, mobility, joint function, pulmonary function, and reduced liver and spleen size.

In 2011, the American College of Medical Genetics and Genomics issued their Standards and Guidelines for lysosomal storage diseases (Wang, 2011) and recommends that enzyme replacement therapy should be started as soon as possible after diagnosis if this therapeutic option is chosen.

The product information label (Naglazyme, 2013) for galsulfase includes the following Warnings and Precautions:

The recommended dose of galsulfase is 1 mg per kg of body weight given once a week as an intravenous (IV) infusion. Pretreatment with antihistamines with or without antipyretics is recommended 30 to 60 minutes before the start of the infusion (FDA label, 2013).

Definitions

Enzyme replacement therapy: A treatment provided, usually via intravenous infusion, to provide enzymes in an individual unable to make sufficient amounts of that enzyme on their own.

Glycosaminoglycans: Any of several polysaccharides derived from an amino hexose that are components of mucoproteins, glycoproteins, and blood-group substances; also known as mucopolysaccharide.

Mucopolysaccharidoses: A group of genetic lysosomal storage diseases which is caused by the body's inability to produce specific enzymes.

Mucopolysaccharidosis type VI: One type of mucopolysaccharidosis in which the body's tissues and organs enlarge and become inflamed or scarred causing skeletal abnormalities, cardiac disease, hearing and vision loss.

References

Peer Reviewed Publications:

  1. 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(8):1953-1964.
  2. Harmatz PR, Garcia P, Guffon N, et al. Galsulfase (Naglazyme® ) therapy in infants with mucopolysaccharidosis VI. J Inherit Metab Dis. 2014; 37(2):277-287.
  3. Harmatz P, Giugliani R, Schwartz I, et al. Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study. J Pediatr. 2006; 148(4):533-539.
  4. Harmatz P, Kramer WG, Hopwood JJ, et al. Pharmacokinetic profile of recombinant human N-acetylgalactosamine 4-sulphatase enzyme replacement therapy in patients with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): a phase I/II study. Acta Paediatr Suppl. 2005; 94(447):61-68.
  5. Harmatz P, Whitley CB, Waber L, et al. Enzyme replacement therapy in mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). J Pediatr. 2004; 144(5):574-580.
  6. Lin HY, Chuang CK, Wang CH, et al. Long-term galsulfase enzyme replacement therapy in Taiwanese mucopolysaccharidosis VI patients: A case series. Mol Genet Metab Rep. 2016; 7:63-69.
  7. Lin SP, Shih SC, Chuang CK, et al. Characterization of pulmonary function impairments in patients with mucopolysaccharidoses--changes with age and treatment. Pediatr Pulmonol. 2014; 49(3):277-284.
  8. Valayannopoulos V, Nicely H, Harmatz P, Turbeville S. Mucopolysaccharidosis VI. Orphanet J Rare Dis. 2010; 5:5.
  9. Wood T, Bodamer OA, Burin MG, et al. Expert recommendations for the laboratory diagnosis of MPS VI. Mol Genet Metab. 2012; 106(1):73-82.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Brunelli MJ, Atallah ÁN, da Silva EM. Enzyme replacement therapy with galsulfase for mucopolysaccharidosis type VI. Cochrane Database Syst Rev. 2016(3):CD009806.
  2. Galsulfase. In: DrugPoints System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated September 12, 2014. Available at: http://www.micromedexsolutions.com. Accessed on July 5, 2017.
  3. Galsulfase Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS® ) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised January 1, 2006. Accessed on July 5, 2017.
  4. Naglazyme [Product Information]. Novato, CA. BioMarin Pharmaceutical Inc.; March 2013. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125117s111lbl.pdf. Accessed on July 5, 2017.
  5. Wang RY, Bodamer OA, Watson MS, et al. Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals. Genet Med. 2011; 13(5):457-484.
Websites for Additional Information
  1. National MPS Society. Available at: http://mpssociety.org/. Accessed on July 5, 2017.
  2. National Organization for Rare Disorders. Available at: http://rarediseases.org/. Accessed on July 5, 2017.
Index

Galsulfase
Naglazyme

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Revised 08/03/2017 Medical Policy & Technology Assessment Committee (MPTAC) review. Clarification to MN statement. Updated Discussion/General information and References sections.
Reviewed 02/02/2017 MPTAC review. Updated Discussion/General Information and Reference sections.
New 11/03/2016 MPTAC review. Initial document development.