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

 

Compliance is key to achieve sustained results with NAGLAZYME® (galsulfase) therapy1,2

Enzyme replacement therapy (ERT) is lifelong. In order for the patient to benefit from the treatment, NAGLAZYME® (galsulfase) must be infused regularly, on a weekly basis. If therapy stops, glycosaminoglycans will again build up, and symptoms may return. It is important to help patients and families understand that results vary and some improvements occur over a long period of time.

Phase 3 data and long-term survey data show that compliance with weekly infusions results in sustained improvement in endurance, pulmonary function, and urinary glycosaminoglycan levels.1,2

Clinicians can aid in compliance by helping patients and caregivers to manage key deterrents, such as IV pain as well as logistical issues.

Improving compliance with NAGLAZYME treatment

Compliance with NAGLAZYME therapy is key to successful MPS VI treatment. It is therefore critical that clinicians proactively address issues that may affect compliance over the long term.3 Here are some key issues and ways to address them:

  • Patients with MPS VI may have difficulty making infusion appointments due to work and school obligations or frequent illness or hospitalization
    • Be as flexible as possible in scheduling or rescheduling appointments
  • Painful IV insertion can be a cause for anxiety, which could reduce compliance
  • Transportation and other problems may arise

BioMarin RareConnections can help you in supporting patients and parents with reimbursement difficulties and other logistical challenges. Learn more.

Intravenous (IV) access and pain control

Venipuncture is a painful procedure, and a cause of considerable anxiety in children. IV access in patients with MPS VI can present a special challenge due to:

  • Thickened, rough skin
  • Kinked veins
  • Stiff joints (which can make it difficult for patients to straighten their arms)

Strategies to avoid IV challenges

Pain control and reduction of anxiety with IV access should be addressed at the initiation of therapy. Methods to reduce discomfort include3:

  • Topical anesthetics
  • Warming the limb prior to venipuncture
  • Advising the patient and parents to maintain good hydration before infusion
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It is recommended that the clinician consult a child life specialist prior to the first infusion and again as needed.

Patient education and support

Caring for patients with chronic conditions poses specific challenges. While many patients and families are well informed about MPS VI, they may still have a range of questions and concerns. Therefore, it’s important to:

  • Educate patients and their families regarding their treatment options
  • Encourage families to speak to others who have had experience with MPS VI and enzyme replacement therapy

Be a patient advocate

Patients with MPS VI often face pain and debility, leading to emotional and psychological problems.4 To help patients, clinicians are encouraged to provide strong psychosocial support by5:

  • Engaging in individual counseling
  • Encouraging interaction with a multidisciplinary team of providers
  • Promoting support groups and communication with other patients and caregivers5,6

Some patients may be able to receive their NAGLAZYME infusions at home »

References: 1. Harmatz P, Giugliani R, Schwartz IVD, et al; MPS VI Study Group. Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI: final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase. Mol Genet Metab. 2008;94(4):469-475. doi:10.1016/j.ymgme.2008.04.001. 2. 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. 3. NAGLAZYME [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2019. 4. Holley UA. Social isolation: a practical guide for nurses assisting clients with chronic illness. Rehabil Nurs. 2007;32(2):51-56. 5. Wilcox WR. Lysosomal storage disorders: the need for better pediatric recognition and comprehensive care. J Pediatr. 2004;144(5 suppl):S3-S14. 6. Lindeke LL, Leonard BJ, Presler B, Garwick A. Family-centered care coordination for children with special needs across multiple settings. J Pediatr Health Care. 2002;16(6):290-297.
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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.