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

 

MPS VI patient care

The multiple impacts of MPS VI require a combined strategy to manage specific symptoms while targeting underlying disease with enzyme replacement therapy (ERT). Early treatment may optimize outcomes and the potential benefits of ERT with NAGLAZYME® (galsulfase).1

Integrated care, usually supervised by a clinical geneticist, will involve multiple specialists to address specific needs.2 Throughout treatment, regular multisystem monitoring and assessments are a must.2 As patients age, it is important to plan the transition to adult care to ensure that the appropriate care is in place.3

Integrated disease management

According to the 2019 management guidelines for mucopolysaccharidosis VI, integrated management of the progressive, multisystemic disease manifestations is essential.2 Although treatment options have been limited in the past, enzyme replacement therapy with NAGLAZYME has demonstrated enduring benefits with long-term therapy and improved the outlook for patients with MPS VI.4

Symptom-based care: it takes a team

While targeting the underlying disease, the coordinating clinician will also need to arrange for symptom-based care by specialists equipped to address the specific manifestations of the disease. Here are some key issues and recommended referrals5:

  • Valvular heart disease: refer to a cardiologist
  • Conductive and sensorineural hearing loss: refer to an audiologist for periodic hearing evaluations
  • Corneal clouding and eventual significant visual impairment: refer to an ophthalmologist for initial and follow-up slit-lamp and fundoscopic exams
  • Spinal cord compression secondary to thickening of the dura in the cervical canal (leads to myelopathy): refer to a neurosurgeon or orthopedist
  • Airway obstruction, hyperventilation, and sleep apnea: refer to a pulmonologist for regular evaluation

cta-table

Specific treatment for symptoms associated with MPS VI5-9

Click to view.

Symptom-based procedures

Symptom-based treatment addresses individual complications of MPS VI as they arise, and may include10:

  • Antibiotics and other symptom-based medications
  • Pain management
  • Surgery
  • Adaptive or supportive devices
  • Physical or occupational therapy

The transition to adult care3

As MPS VI patients age, it is important to plan the transition to adulthood, to ensure that the appropriate support is extended beyond the scope of pediatric care and parental supervision. This transition should be tailored to each patient’s specific needs, so that those who can take over their own care have the tools they need, and those with limited capacities have the appropriate care and services in place to support them.3

Planning required3

The transition to adult care should include assessment of a patient’s capacities to determine what he or she may be able to handle. Much of that consideration revolves around the patient’s ability to communicate information about his or her condition. With that determination made, the right choices for continuing care should be offered. It is important to remember that this process is very gradual. The pediatric geneticist or other clinician coordinating the MPS VI patient’s care may need to oversee the transition until the patient has achieved his or her capabilities and is integrated into the adult system. It is important to have a formal, site-specific transition strategy that includes joint visits with the pediatrician and adult patient physician. Families and patients should be encouraged to be involved in this process.11

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References: 1. 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. 2. 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. 3. Hendriksz C. Developing a best practice model of transition in the UK. Presented at: 12th International Symposium on MPS and Related Diseases; June 29, 2012; Noordwijkerhout, The Netherlands. 4. 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. 5. 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. 6. NAGLAZYME [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2019. 7. Swiedler SJ, Beck M, Bajbouj M, et al. Threshold effect of urinary glycosaminoglycans and the walk test as indicators of disease progression in a survey of subjects with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). Am J Med Genet A. 2005;134A(2):144-150. 8. Lachman RS, Burton BK, Clarke LA. Mucopolysaccharidosis IVA (Morquio A syndrome) and VI (Maroteaux-Lamy syndrome): under-recognized and challenging to diagnose. Skeletal Radiol. 2014;43(3):359–369. doi:10.1007/s00256-013-1797-y. 9. Wraith JE. The mucopolysaccharidoses: a clinical review and guide to management. Arch Dis Childhood. 1995;72(3):263-267. 10. Wilcox WR. Lysosomal storage disorders: the need for better pediatric recognition and comprehensive care. J Pediatr. 2004;144(5 suppl):S3-S14. 11. American Academy of Pediatrics, American Academy of Family Physicians, American College of Physicians, Transitions Clinical Report Authoring Group, Cooley WC, Sagerman PJ. Supporting the health care transition from adolescence to adulthood in the medical home. Pediatrics. 2011;128(1):182-200. doi:10.1542/peds.2011-0969.
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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.