Summary

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• This summary is based on the review of three randomized controlled trial(s). ^[1-3]
• Vestronidase alfa demonstrated significant reductions in urinary glycosaminoglycans (uGAG) levels across all studies, with a least square mean percentage change of -60% at week 4 and -61% at week 48 in the Phase II study, and sustained reductions over 144 weeks in the Phase 3 extension study.
• In pediatric subjects, the Phase II study showed improvements in growth and the resolution of hepatosplenomegaly, with 5 out of 6 subjects resolving hepatomegaly and 2 out of 2 resolving splenomegaly. Positive clinical improvements, including reduced fatigue and enhanced multi-domain responder index scores, were also observed in the Phase 3 study.
• Compared to other enzyme replacement therapies (ERT), vestronidase alfa exhibited a longer enzymatic half-life in fibroblasts (40 days vs. 3-4 days) and demonstrated enhanced beta-glucuronidase activity, showing superior effectiveness in preclinical models.
• In the Phase II study, mild-to-moderate infusion-associated reactions occurred in 50% of subjects, but no new safety signals were identified.
• In the Phase 3 and extension studies, most adverse events were mild to moderate, with no discontinuations due to adverse events and no notable changes in standard safety chemistry panels. Additionally, anti-drug antibodies were detected in some patients, but there was no association with infusion-related reactions.
• In pediatric subjects (<5 years) in the Phase II study, significant reductions in urinary GAG levels were observed, with improvements in growth and resolution of hepatosplenomegaly. In subjects aged 8-25 years, sustained urinary GAG reduction and clinical benefits were observed in the Phase 3 and extension studies. The presence of anti-drug antibodies did not affect the efficacy in reducing urinary GAG levels across these populations.