| dc.description | Vestronidase alfa (recombinant human beta-glucuronidase) is an
enzyme replacement therapy for mucopolysaccharidosis type VII
(MPS VII), a highly heterogeneous, ultra-rare disease. Twelve
subjects, ages 8???25 years, completed a Phase 3, randomized,
placebo-controlled, blind-start, single crossover study (UX003-
CL301; NCT02230566), receiving 24???48 weeks of vestronidase alfa
4 mg/kg IV. All 12 subjects completed the blind-start study, which
showed significantly reduced urinary glycosaminoglycans (uGAG)
and clinical improvement in a multi-domain responder index, and
enrolled in a long-term, open-label, extension study (UX003-CL202;
NCT02432144). Here, we report the final results of the extension
study, up to an additional 144 weeks after completion of the blindstart
study. Three subjects (25%) completed all 144 weeks of study,
eight subjects (67%) ended study participation before Week 144 to
switch to commercially available vestronidase alfa, and one subject
discontinued due to non-compliance after receiving one infusion of
vestronidase alfa in the extension study. The safety profile of
vestronidase alfa in the extension study was consistent with
observations in the preceding blind-start study, with most adverse
events mild to moderate in severity. There were no treatment or
study discontinuations due to AEs and no noteworthy changes in a
standard safety chemistry panel. There was no association between
antibody formation and infusion associated reactions. Subjects
receiving continuous vestronidase alfa treatment showed a sustained
uGAG reduction and clinical response evaluated using a multidomain
responder index that includes assessments in pulmonary
function, motor function, range of motion, mobility, and visual
acuity. Reductions in fatigue were also maintained in the overall
population. Results from this study show the long-term safety and
durability of clinical efficacy in subjects with MPS VII with long-term
vestronidase alfa treatment. | |
