Mucopolysaccharidosis (MPS) VII is an ultra-rare, progressively debilitating, life-threatening lysosomal disease caused by deficiency of the enzyme, β-glucuronidase. Vestronidase alfa is an approved enzyme replacement therapy for MPS VII. UX003-CL301 was a phase 3, randomized, placebo-controlled, blind-start study examining the efficacy and safety of vestronidase alfa 4 mg/kg intravenously administered every 2 weeks to 12 patients with MPS VII. Due to the rarity of disease, broad eligibility criteria resulted in a highly heterogeneous population with variable symptoms. For an integrated view of the diverse data, the changes from baseline (or randomization for the placebo period) in clinical endpoints were grouped into three functional domains (mobility, fatigue, and fine motor + self-care) and analyzed post-hoc as subject-level heat maps. Mobility assessments included the 6-minute walk test, 3-minute stair climb test, Bruininks-Oseretsky test (BOT-2) gross motor function subtests, and patient-reported outcome assessments (PROs) related to movement, pain, and ambulation. Fatigue assessments included the Pediatric Quality of Life Multidimensional Fatigue Scale and other fatigue-related PROs. Fine motor + self-care assessments included BOT-2 fine motor function subtests and PROs for eating, dressing, hygiene, and caregiver assistance. Most subjects showed improvement in at least one domain. Two subjects improved in two or more domains and two subjects did not show clear improvement in any domain. Both severely and mildly affected subjects improved with vestronidase alfa in clinical assessments, PRO results, or both. Heat map analysis demonstrates how subjects responded to treatment across multiple domains, providing a useful visual tool for studying rare diseases with variable symptoms.
Bibliographical noteFunding Information:
C.H., W.S., T.C., and C.-Y.C. are employees and shareholders of Ultragenyx Pharmaceutical Inc. C.B.W., R.Y.W., M.B., and P.H. have served as clinical investigators in clinical trials with the product manufactured by Ultragenyx Pharmaceutical Inc. The content of the article has not been influenced by the sponsors. Dr. Harmatz has received support for this project from the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through UCSF-CTSI grant number UL1 TR000004. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
- MPS VII
- Sly syndrome
- enzyme replacement therapy
- heat map
- vestronidase alfa