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

• Published in: Molecular genetics and metabolism Vol. 94; no. 4; pp. 469 - 475
• Main Authors: Harmatz, Paul, Giugliani, Roberto, D. Schwartz, Ida Vanessa, Guffon, Nathalie, Teles, Elisa Leão, Miranda, M. Clara Sá, Wraith, J. Edmond, Beck, Michael, Arash, Laila, Scarpa, Maurizio, Ketteridge, David, Hopwood, John J., Plecko, Barbara, Steiner, Robert, Whitley, Chester B., Kaplan, Paige, Yu, Zi-Fan, Swiedler, Stuart J., Decker, Celeste
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2008
• Subjects: Adolescent; Adult; Child; Child, Preschool; Clinical trial; Enzyme replacement therapy; Female; Follow-Up Studies; Glycosaminoglycans; Glycosaminoglycans - urine; Humans; Male; Motor Activity; Mucopolysaccharidosis VI; Mucopolysaccharidosis VI - physiopathology; Mucopolysaccharidosis VI - therapy; N-Acetylgalactosamine-4-sulfatase; N-Acetylgalactosamine-4-Sulfatase - administration & dosage; N-Acetylgalactosamine-4-Sulfatase - adverse effects; N-Acetylgalactosamine-4-Sulfatase - therapeutic use; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Treatment Outcome; Walking; Mucopolysaccharidosis VI; Clinical trial; N-Acetylgalactosamine-4-sulfatase; Glycosaminoglycans; Enzyme replacement therapy
• ISSN: 1096-7192; 1096-7206; 1096-7206
• DOI: 10.1016/j.ymgme.2008.04.001

The objective of this study was to evaluate the long-term clinical benefits and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome), a lysosomal storage disease. Fifty-six patients derived from 3 clinical studies were followed in open-label extension studies for a total period of 97–260 Weeks. All patients received weekly infusions of rhASB at 1 mg/kg. Efficacy was evaluated by (1) distance walked in a 12-minute walk test (12MWT) or 6-minute walk test (6MWT), (2) stairs climbed in the 3-minute stair climb (3MSC), and (3) reduction in urinary glycosaminoglycans (GAG). Safety was evaluated by compliance, adverse event (AE) reporting and adherence to treatment. Results: A significant reduction in urinary GAG (71–79%) was sustained. For the 12MWT, subjects in Phase 2 showed improvement of 255 ± 191 m (mean ± SD) at Week 144; those in Phase 3 Extension demonstrated improvement from study baseline of 183 ± 26 m (mean ± SE) in the rhASB/rhASB group at Week 96 and from treatment baseline (Week 24) of 117 ± 25 m in the placebo/rhASB group. The Phase 1/2 6MWT and the 3MSC from Phase 2 and 3 also showed sustained improvements through the final study measurements. Compliance was 98% overall. Only 560 of 4121 reported AEs (14%) were related to treatment with only 10 of 560 (2%) described as severe. Conclusion: rhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile.