Clinically significant improvements with NAGLAZYME® (galsulfase) therapy

Phase 3 pivotal trial

In the randomized, double‐blind, multicenter, placebo‐controlled clinical trial, 39 patients with MPS VI received 1 mg/kg NAGLAZYME® (galsulfase) or placebo once‐weekly for 24 weeks, then for an extension of 72 weeks, for a total of up to 96 weeks. Enrollment was restricted to patients with a 12‐minute walk distance of 5 to 400 meters. All patients were treated with antihistamines prior to each infusion. Results from the 10-year Resurvey study, which evaluated patients who were involved in the initial Survey Study, are consistent with the phase 3 trial results.1-3

NAGLAZYME improved endurance as shown by the 12‐minute walk test (12MWT) 1,2,4

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

_2-1a-12_minute_walk_test_Rd1_M

Week 24: Patients treated with NAGLAZYME demonstrated statistically and clinically significant improvement in endurance compared to placebo as measured by a 12MWT at week 24.1

Week 96: In the group originally treated with NAGLAZYME, improvement in the 12MWT was sustained through week 96.2

  • At week 96 the group treated with NAGLAZYME showed a 183 ± 26 m improvement from baseline

As exemplified by these clinical trial data, the walk test has emerged as a proven, trusted, and relatively simple method of measuring endurance in patients with MPS VI. The test demonstrates how performance impairment is a measure of disease progression.6

Weekly infusions with NAGLAZYME maintained long-term improvement in endurance.3»

NAGLAZYME improved the rate of stair‐climbing1,2,4

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

_2-1b-3_minute_stairclimb_test_Rd1_M

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

Week 24: Patients treated with NAGLAZYME demonstrated improvement in the 3‐minute stair climb compared to placebo at week 24, though statistical significance was not reached (P=0.053).1,4

Week 96: In the group originally treated with NAGLAZYME, improvement in the rate of stair‐climbing was demonstrated at week 96.2

  • At week 96, the group treated with NAGLAZYME showed an improvement of 13.1 ± 2.0 stairs/min over baseline

NAGLAZYME reduced urinary glycosaminoglycan (uGAG) levels1,2

uGAG levels in patients taking NAGLAZYME vs placebo1,2

_2-1c-galsulfase_reduced_Rd1_M

Week 24: In patients treated with NAGLAZYME, mean uGAG levels were reduced by 75% at week 24, a significantly greater reduction than patients on placebo (P<0.001).1

Week 96: In the group originally treated with NAGLAZYME, the reduction in uGAG levels was sustained through week 96. From week 48 to week 96, no change in uGAG levels was observed in the NAGLAZYME group.1,2

Overall, 95% of patients showed at least a 50% reduction in uGAG levels after 72 weeks of treatment with NAGLAZYME.4

Learn more about the long-term data regarding uGAG levels with NAGLAZYME3 »

Patients treated with NAGLAZYME for 96 weeks demonstrated improvement in pulmonary function6

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

_2-1d-mean_percent_change_Rd1_M

Week 96: By 96 weeks of treatment increases in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) averaged approximately 10% and 13%, respectively, for patients <12 years of age6

  • For patients ≥12 years of age, FEV1 and FVC did not improve relative to baseline in the first 24 weeks but showed meaningful improvement in subsequent weeks

At 96 weeks of treatment, FEV1 and FVC improved from baseline by approximately 13% and 23%, respectively.6

Regardless of phenotype or age, NAGLAZYME improves pulmonary function over the long-term.3 »

Learn more about the sustained benefits of NAGLAZYME »

References: 1. Harmatz P, Giugliani R, Schwartz I, et al; MPS VI Phase 3 Study Group. 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. doi:10.1016/j.jpeds.2005.12.014. 2. 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. 3. 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. 4. NAGLAZYME [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2013. 5. McDonald A, Steiner R, Kuehl K, Turbeville S. Clinical utility of endurance measures for evaluation of treatment in patients with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). J Pediatr Rehabil Med. 2010;3(2):119-127. doi:10.3233/PRM-2020-0114. 6. Harmatz P, Yu Z-F, Giugliani R, et al. Enzyme replacement therapy for mucopolysaccharidosis VI: evaluation of long-term pulmonary function in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase. J Inherit Metab Dis. 2010;33(1):51-60. doi:10.1007/s10545-009-9007-8.

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 (galsulfase) 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 1-866-906-6100, or FDA at 1-800-FDA-1088 or go to www.fda.gov/medwatch.

Please see full Prescribing Information.