Long-term efficacy and safety of vestronidase alfa enzyme replacement therapy in pediatric subjects < 5 years with mucopolysaccharidosis VII

Dose-dependent effects of enzyme replacement therapy on skeletal disease progression in mucopolysaccharidosis VII dogs

“…Positive clinical findings reported to date in patients receiving vestronidase alfa include reductions in liver and spleen size, improved pulmonary function, decreased fatigue, and improvements in general overall wellbeing. 15 , 16 , 17 , 24 While there is little data on the skeletal disease response, trends toward improved joint function and growth velocity have been reported in some patients. 16 , 17 Drawing conclusions on the skeletal response from these clinical studies is challenging given the broad spectrum of disease severity observed among study participants, and the limited number of patients available for study.…”

“… 15 , 16 , 17 , 24 While there is little data on the skeletal disease response, trends toward improved joint function and growth velocity have been reported in some patients. 16 , 17 Drawing conclusions on the skeletal response from these clinical studies is challenging given the broad spectrum of disease severity observed among study participants, and the limited number of patients available for study. An early preclinical study in newborn MPS VII mice found that intravenous GUSB administration resulted in improved long bone lengths and skull morphology, and reduced GAG storage in osteoblasts, but no such reduction in chondrocytes 18 ; and, recently, it was shown that doses of vestronidase alfa up to 20 mg/kg administered to MPS VII mice resulted in higher relative enzyme activities in several tissues including kidney and lung, but not bone.…”

“… 16 There is limited information from early clinical studies and case reports on how effective ERT is for treating the skeletal manifestations of MPS; however, it has been reported that some MPS VII patients receiving ERT exhibit improvements in growth, joint range of motion and mobility, suggesting a positive effect on skeletal disease. 16 , 17 Studies in MPS VII mice suggest that ERT ameliorates, at least partially, skeletal pathology and improves bone growth, but the administered enzyme does not reach all involved cell types. 18 …”

Applying real-world data from expanded-access (“compassionate use”) patients to drug development

“…Clinical evidence included 22 patients in two efficacy studies and an EA protocol. Between 2017 and 2018, three other drug approvals included EA protocols: vestronidase to treat mucopolysaccharidosis VII, a rare genetic enzyme deficiency [10,11]; lutetium 177 dotatate injection, a radiolabeled drug for rare gastroenteropancreatic neuroendocrine tumors [12][13][14]; and cannabidiol, an adjunctive treatment for seizures associated with two rare conditions [15].…”