Global Medical Expert Ultragenyx Pharmaceutical Inc. Novato, California, United States
Background: Non-immune hydrops fetalis (NIHF) is a potentially life-threatening manifestation of mucopolysaccharidosis VII (MPS VII), a heterogeneous, ultra-rare lysosomal storage disease. The incidence of NIHF is approximately 40% in patients with MPS VII. NIHF is often fatal, and the reported one-year mortality rate among infants born with NIHF is >40%.
Design/Methods: Requests were received for vestronidase alfa as enzyme replacement therapy for MPS VII, either prospectively for fetuses diagnosed in utero or for infants diagnosed <1 year of age.
Results: We compiled real-world data on 37 treatment-naïve patients (Europe/Turkey, n=14; US, n=13; Latin America, n=9; India, n=1). Twenty-five (68%; 25/37) patients had confirmed NIHF, 8 (22%; 8/37) patients were without NIHF, and 4 (11%; 4/37) patients had unknown NIHF status (Table). Of the 25 patients with NIHF, 13 (52%; 13/25) patients died before initiation of treatment (including 3 patients who died in utero) and 2 (8%; 2/25) patients died following complications of MPS VII while on treatment with vestronidase alfa (approximates a 60% one-year mortality rate). Ten (40%; 10/25) patients with NIHF survived >1 year, including 6 patients who received vestronidase alfa before age 1 and 4 patients who received vestronidase alfa after age 1. All 8 patients without NIHF survived >1 year (0% one-year mortality rate), 7 of whom received vestronidase alfa. Three of 4 patients with unknown NIHF status did not survive >1 year, and the outcome of the fourth patient is unknown. None of the patients with unknown NIHF status received vestronidase alfa. Overall, 19 patients received vestronidase alfa, including 12 with NIHF and 7 without NIHF. No patients received in utero treatment. Conclusion(s): These results demonstrate an urgent unmet need in patients with MPS VII who have NIHF and underscore the importance of newborn screening and MPS VII confirmation to allow for timely consideration of treatment options, including vestronidase alfa. Additional strategies, such as in utero administration of vestronidase alfa or increased dosing of vestronidase alfa, may address the unmet need, and require evaluation.
Table. Summary of Outcomes Among Patients According to NIHF Status
Authors/Institutions: Deborah Marsden, Ultragenyx Pharmaceutical Inc, Novato, California, United States; Camille Bedrosian, Ultragenyx Pharmaceutical Inc, Novato, California, United States; Tobin Chettiath, Ultragenyx Pharmaceutical Inc, Novato, California, United States; Kirin Jamison, Ultragenyx Pharmaceutical Inc, Novato, California, United States