Introduction:
MPS VII is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by beta-glucuronidase (GUSB) enzyme deficiency. Enzyme replacement therapy with vestronidase alfa (VA), a recombinant human GUS, is approved for MPS VII treatment.

Methods:
The DMP is an ongoing, multicenter, observational study collecting standardized real-world data from patients with MPS VII treated with VA or any other management approach. Patient demographics, VA safety and efficacy, and clinical outcomes were collected. The PedsQL assesses general, sleep/rest, and cognitive fatigue. The MPS HAQ assesses mobility, self-care, and caregiver assistance.

Results:
The DMP includes 35 patients actively contributing data. Mean (SD) age at diagnosis was 4.5 (4.0) years. Mean (SD) age at enrollment was 13.6 (11.1) years. Intellectual disability was reported for 18 patients (51%): 5 profound, 5 severe, 2 moderate, 5 mild, and 1 unreported. Patients have been followed for up to 9 years, including patients in prior clinical trials. Among the 28 patients who had received VA, 12 (43%) were <5 years old when they initiated VA, 9 (32%) were ≥5 to <12, 5 (18%) were ≥12 to <18, and 2 (7%) were ≥18. Mean (SD) age of initiation was 8.2 (6.3) years.

At DMP baseline, all patients showed a deficit on the 6MWT; percent predicted values ranged from 8-87% (n=21, ≥5 years old). The PedsQL total fatigue scores (n=25, ≥2 years old) ranged from 44-97/100 across domains, with high scores representing less fatigue. Mean (SD) Peds QL values for healthy individuals are 72 (15). Baseline MPS HAQ mobility and self-care scores (n=22, ≥5 years old) ranged from 0 (no difficulty or independent) to 10 (unable to perform or extremely difficult). Caregiver assistance scores ranged from 1 (minimal assistance required) to 39 (complete assistance required).

Based on medical history, sixteen patients in the DMP (28%) had a history of non-immune hydrops fetalis (NIHF) or similar neonatal presentations. Though NIHF is known to be prevalent among patients with MPS VII, only four patients were diagnosed before 1 year of age. Rates of intellectual disability among patients with NIHF were higher relative to those without NIHF and intellectual disability was more severe. All 10 patients with NIHF and intellectual disability had at least moderate intellectual disability (63% of patients with NIHF), while only two patients without NIHF had at least moderate intellectual disability (11%; P=0.004 by Fisher’s exact t-test). Nearly all patients with NIHF had received VA (94%), and 13 (68%) of those without NIHF had received VA.

Percent predicted values on the 6MWT trended slightly lower among patients with NIHF (n=9; range 19-71%) than those without (n=12; range 8-87%). Peds QL total fatigue scores were similar among patients with NIHF (n=13; range 44-97/100) and those without (n=12; 50-89/100), with higher scores indicating less fatigue. MPS HAQ scores for mobility were similar among patients with NIHF (n=11) and those without (n=11) with both ranging from 0 to 10. Patients with NIHF may have required more help with self-care (NIHF: 1-10/10; no NIHF: 0-8/10) and more caregiver assistance (NIHF: 5-39/39; no NIHF: 1-39/39). Higher scores infer worse mobility, less ability to perform self-care, and more caregiver assistance needed.

No new safety concerns were identified, and the benefit-risk profile of VA remains positive in children and adults with MPS VII.

Conclusion:
The DMP is a significant study to further advance understanding of the complex clinical heterogeneity of MPS VII. Patients with NIHF represent an especially vulnerable population that may benefit from early detection and treatment. The benefit-risk profile of VA continues to be favorable for use in children and adults with MPS VII. Enrollment is ongoing, and patients continue to be assessed.