The Progression of MPS VI

12-minute walk test: mean meters walked1,2,4 a,b

3-minute stair climb test: mean stairs per minute1,2,4 a

a Fitted values.2

b By week 96, patients in the drug group had been taking NAGLAZYME for 96 weeks; patients in the placebo group had only been taking NAGLAZYME for the 72-week open-label extension period.2

c One patient in the placebo group left the study for reasons unrelated to treatment. Patients receiving placebo were switched to NAGLAZYME in the trial extension period.1

d One patient failed to complete the assessment.2

uGAG levels in patients taking NAGLAZYME vs placebo1,2

Mean percent change in height and pulmonary function by treatment week and age group over all available patient data6

Improvements in endurance in patients who completed the walk test at follow-up1

Pulmonary function across all age groups in the ERT-treated patients1

Urinary GAG levels in all ERT‐treated patients1

Urinary GAG levels >200 μg/mg are associated with rapidly progressing disease; uGAG levels ≤200 μg/mg are associated with slowly progressing disease.4

Resurvey Study endurance results of patients with uGAG levels ≤200 μg/mg

 

Diagnosing MPS VI

Diagnosis of MPS VI is usually prompted through clinical presentation.1 Elevated urinary glycosaminoglycan levels suggest a mucopolysaccharidosis disorder.1 MPS VI is diagnosed by testing arylsulfatase B (ASB) activity in blood or fibroblasts. MPS VI is confirmed when ASB enzyme activity in the leukocytes or fibroblasts is determined to be low as judged against a reference enzyme and the laboratory’s own reference ranges.2

When to suspect MPS VI

Because patients with MPS VI present with a variety of signs and symptoms, it is essential to maintain a high index of suspicion and pay close attention to the medical history.3 Suspicious signs and symptom clusters may include3:

  • Macrocephaly
  • Dysmorphic facial features
  • Short stature
  • Enlarged tongue
  • Enlarged tonsils and adenoids
  • Corneal clouding
  • Impaired vision
  • Short neck
  • Difficulty swallowing
  • Noisy breathing
  • Umbilical or inguinal hernias
  • Sinopulmonary infections
  • Heart murmur
  • Valve disease

Refer promptly

Once a clinical suspicion has been raised, all patients with suspected MPS VI should be referred promptly to a geneticist for definitive diagnosis and appropriate counseling.4

Benefits of early diagnosis

When MPS VI is recognized promptly and patients are carefully managed, its harmful effects may be minimized. That’s because early diagnosis of MPS VI can allow for early treatment that optimizes the potential benefits of enzyme replacement therapy with NAGLAZYME® (galsulfase).5 In clinical trials, NAGLAZYME has been shown to improve walking and stair‐climbing.6 This improvement can be maintained with long‐term therapy. A study that measured the 6‐minute walk test in patients with MPS VI, many of whom had been on NAGLAZYME therapy for a long time (an average of 6.8 years), showed that improvements in endurance lasted when patients kept taking NAGLAZYME.7

Learn more about the long-term efficacy of NAGLAZYME »

The dangers of delayed diagnosis

Both the slowly and rapidly progressing forms of MPS VI result in significant declines in physical functioning and well-being, as well as a shortened lifespan.1 A 2018 literature review found the median delay in diagnosis for patients with MPS VI was 4.7 years.8

Once multisystemic damage occurs, it cannot be reversed. Treatment, however, may help to restore endurance and slow the rate of disease progression.5,6

Growth and skeletal abnormalities are common in undiagnosed MPS VI

  • Accelerated growth in infancy coupled with advanced bone maturation is often followed by slowing growth in the first few years of life and short stature9
  • Final height may range from extreme to mild short stature9
  • MPS disorders have a common radiological expression known as dysostosis multiplex that involves almost all of the bony skeleton10

Cardiac abnormalities: also common in MPS VI1

Cardiac disorders are common in MPS VI and a frequent cause of morbidity and mortality.

  • Cardiac disorders most commonly manifest as progressive valve degeneration with stenosis or insufficiency
  • Other manifestations include:
    • Electrocardiographic abnormalities
    • Systemic vascular narrowing and hypertension
    • Endocarditis

    Learn more about caring for patients with MPS VI »

    References: 1. Akyol MU, Alden TD, Amartino H, et al. Recommendations for the management of MPS VI: systematic evidence- and consensus-based guidance. Orphanet J Rare Dis. 2019;14:118. 2. Wood T, Bodamer OA, Curin MG, D’Almeida V, et al. Expert recommendations for the laboratory diagnosis of MPS VI. Mol Genet Metab. 2012;106(1):73-82. 3. Wilcox WR. Lysosomal storage disorders: the need for better pediatric recognition and comprehensive care. J Pediatr. 2004;144(5 suppl):S3-S14. 4. Harmatz PR. Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI). Medscape website. https://emedicine.medscape.com/article/946474-overview. Updated March 20, 2017. Accessed November 17, 2020. 5. 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. 6. NAGLAZYME [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2019. 7. 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. doi: 10.1002/ajmg.a.36584. 8. Clarke L, Ellaway C, Foster HE, et al. Understanding the early presentation of mucopolysaccharidoses disorders: results of a systematic literature review and physician survey. J Inborn Errors Metab Screen. 2018;6:1-12 (supplemental file). 9. Heron D, Baumann C, Benichou JJ, Harpey JP, Le Merrer M. Early diagnosis of Maroteaux-Lamy syndrome in two patients with accelerated growth and advanced bone maturation. Eur J Pediatr. 2004;163(6):323-326. 10. White KK. Orthopaedic aspects of mucopolysaccharidoses. Rheumatology. 2011;50(suppl 5):v26-v33.
+

Important Safety Information

INDICATION

NAGLAZYME® (galsulfase) is indicated for patients with mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome). NAGLAZYME has been shown to improve walking and stair-climbing capacity.

IMPORTANT SAFETY INFORMATION

Life-threatening anaphylactic reactions and severe allergic reactions have been observed in some patients during NAGLAZYME infusions and up to 24 hours after infusion. If these reactions occur, immediate discontinuation of NAGLAZYME is recommended and appropriate medical treatment should be initiated, which may include resuscitation, epinephrine, administering additional antihistamines, antipyretics or corticosteroids. In patients who have experienced anaphylaxis or other severe allergic reactions during infusion with NAGLAZYME, caution should be exercised upon rechallenge; appropriately trained personnel and equipment for emergency resuscitation (including epinephrine) should be available during infusions.

As with other enzyme replacement therapies, immune-mediated reactions, including membranous glomerulonephritis have been observed. In clinical trials, nearly all patients developed antibodies as a result of treatment with NAGLAZYME; however, the analysis revealed no consistent predictive relationship between total antibody titer, neutralizing or IgE antibodies, and infusion-associated reactions, urinary glycosaminoglycan (GAG) levels, or endurance measures.

Caution should be exercised when administering NAGLAZYME to patients susceptible to fluid volume overload because congestive heart failure may result. Consider a decreased total infusion volume and infusion rate when administering NAGLAZYME to these patients.

Consideration to delay NAGLAZYME infusion should be given when treating patients who present with an acute febrile or respiratory illness. Sleep apnea is common in MPS VI patients and antihistamine pretreatment may increase the risk of apneic episodes. Evaluation of airway patency should be considered prior to the initiation of treatment. Patients using supplemental oxygen or continuous positive airway pressure (CPAP) during sleep should have these treatments readily available during infusion in the event of an infusion reaction, or extreme drowsiness/sleep induced by antihistamine use.

Pretreatment with antihistamines with or without antipyretics is recommended prior to the start of infusion to reduce the risk of infusion reactions. If infusion reactions occur, decreasing the infusion rate, temporarily stopping the infusion, or administering additional antihistamines and/or antipyretics is recommended.

During infusion, serious adverse reactions included laryngeal edema, apnea, pyrexia, urticaria, respiratory distress, angioedema, and anaphylactoid reaction; severe adverse reactions included urticaria, chest pain, rash, abdominal pain, dyspnea, apnea, laryngeal edema, and conjunctivitis. The most common adverse events (≥10%) observed in clinical trials in patients treated with NAGLAZYME were rash, pain, urticaria, pyrexia, pruritus, chills, headache, nausea, vomiting, abdominal pain and dyspnea. The most common adverse reactions requiring interventions are infusion-related reactions.

Spinal/cervical cord compression is a known and serious complication that is expected to occur during the natural course of MPS VI. Signs and symptoms of spinal/cervical cord compression include back pain, paralysis of limbs below the level of compression, and urinary or fecal incontinence. Patients should be evaluated for spinal/cervical cord compression prior to initiation of NAGLAZYME to establish a baseline and risk profile. Patients treated with NAGLAZYME should be regularly monitored for the development or progression of spinal/cervical cord compression and be given appropriate clinical care.

To report SUSPECTED ADVERSE REACTIONS, contact BioMarin Pharmaceutical Inc. at 1-888-906-6100, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information.

Important Safety Information

INDICATION

NAGLAZYME® (galsulfase) is indicated for patients with mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome). NAGLAZYME has been shown to improve walking and stair-climbing capacity.

IMPORTANT SAFETY INFORMATION

Life-threatening anaphylactic reactions and severe allergic reactions have been observed in some patients during NAGLAZYME infusions and up to 24 hours after infusion. If these reactions occur, immediate discontinuation of NAGLAZYME is recommended and appropriate medical treatment should be initiated, which may include resuscitation, epinephrine, administering additional antihistamines, antipyretics or corticosteroids. In patients who have experienced anaphylaxis or other severe allergic reactions during infusion with NAGLAZYME, caution should be exercised upon rechallenge; appropriately trained personnel and equipment for emergency resuscitation (including epinephrine) should be available during infusions.

As with other enzyme replacement therapies, immune-mediated reactions, including membranous glomerulonephritis have been observed. In clinical trials, nearly all patients developed antibodies as a result of treatment with NAGLAZYME; however, the analysis revealed no consistent predictive relationship between total antibody titer, neutralizing or IgE antibodies, and infusion-associated reactions, urinary glycosaminoglycan (GAG) levels, or endurance measures.

Caution should be exercised when administering NAGLAZYME to patients susceptible to fluid volume overload because congestive heart failure may result. Consider a decreased total infusion volume and infusion rate when administering NAGLAZYME to these patients.

Consideration to delay NAGLAZYME infusion should be given when treating patients who present with an acute febrile or respiratory illness. Sleep apnea is common in MPS VI patients and antihistamine pretreatment may increase the risk of apneic episodes. Evaluation of airway patency should be considered prior to the initiation of treatment. Patients using supplemental oxygen or continuous positive airway pressure (CPAP) during sleep should have these treatments readily available during infusion in the event of an infusion reaction, or extreme drowsiness/sleep induced by antihistamine use.

Pretreatment with antihistamines with or without antipyretics is recommended prior to the start of infusion to reduce the risk of infusion reactions. If infusion reactions occur, decreasing the infusion rate, temporarily stopping the infusion, or administering additional antihistamines and/or antipyretics is recommended.

During infusion, serious adverse reactions included laryngeal edema, apnea, pyrexia, urticaria, respiratory distress, angioedema, and anaphylactoid reaction; severe adverse reactions included urticaria, chest pain, rash, abdominal pain, dyspnea, apnea, laryngeal edema, and conjunctivitis. The most common adverse events (≥10%) observed in clinical trials in patients treated with NAGLAZYME were rash, pain, urticaria, pyrexia, pruritus, chills, headache, nausea, vomiting, abdominal pain and dyspnea. The most common adverse reactions requiring interventions are infusion-related reactions.

Spinal/cervical cord compression is a known and serious complication that is expected to occur during the natural course of MPS VI. Signs and symptoms of spinal/cervical cord compression include back pain, paralysis of limbs below the level of compression, and urinary or fecal incontinence. Patients should be evaluated for spinal/cervical cord compression prior to initiation of NAGLAZYME to establish a baseline and risk profile. Patients treated with NAGLAZYME should be regularly monitored for the development or progression of spinal/cervical cord compression and be given appropriate clinical care.

To report SUSPECTED ADVERSE REACTIONS, contact BioMarin Pharmaceutical Inc. at 1-888-906-6100, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information.