169 Update on Enzyme Replacement Therapy (ERT) with Recombinant Human Arylsulfatase B (RHASB) for MPS VI (Maroteaux-Lamy)

Abstract

MPS VI is a rare, life-threatening lysosomal storage disease with no effective treatment. ERT with rhASB has shown promising results in 2 clinical studies. The objective of this Phase 3 study was to confirm efficacy and safety. 39 patients were enrolled in a randomized, double-blind, placebo-controlled study for 24 weeks. The primary endpoint was the distance walked in 12 minutes (12MWT), while secondary endpoints were the number of stairs climbed in 3 minutes (3MSC), and the level of urinary glycosaminoglycans (GAGs). After 24 weeks, all patients received drug in a 24 week open label extension period. For the Week 1–24 period, the 19 patients receiving rhASB demonstrated a significant mean improvement of 92 meters (m) in the 12MWT as compared to the 20 patients receiving placebo (p=0.025). For the weeks 25 to 48 period, the placebo group, now receiving rhASB, showed a mean increase of 65 m relative to Week 24 (p=0.007). The original rhASB group continuing on treatment during this period improved their mean walk distance an additional 36 m (p=0.15). For the 3MSC, the rhASB group demonstrated a mean improvement of 5.7 stairs/minute after 24 weeks as compared to the placebo group (p=0.053). Relative to 12MWT, similar improvements in 3MSC were observed for each group from Week 24 to Week 48. Upon receiving rhASB, both the rhASB and placebo groups had rapid declines in urinary GAGs (p<0.001). Infusions were generally well tolerated: 98% of possible infusions were received. The majority of adverse events were mild to moderate in severity. All but one patient developed IgG antibodies to rhASB, but these antibodies were not associated with infusion-associated reactions or lack of clinical benefit. rhASB improves physical mobility and endurance, reduces GAGs, and has an acceptable safety profile. Sponsor: BioMarin Pharmaceutical Inc.