Joseph Muenzer, MD, PhD, Pediatric Biochemical Geneticist at University of North Carolina Chapel Hill, discusses results from a phase 1/2 study of tividenofusp alfa in patients with mucopolysaccharidosis II (MPS II; Hunter syndrome).
MPS II is an inherited disorder of carbohydrate metabolism that occurs almost exclusively in males. It is characterized by distinctive facial features, a large head, hydrocephalus, hepatosplenomegaly, umbilical or inguinal hernia, and hearing loss. Individuals with this condition may additionally have joint deformities and heart abnormalities involving the valves. MPS II is caused by genetic changes in the IDS gene.
Tividenofusp alfa is an enzyme replacement therapy, consisting of iduronate-2-sulfatase fused to an engineered transferrin receptor–binding Fc domain, designed to treat neurologic and peripheral manifestations in MPS II. A phase 1/2 open-label study enrolled 47 male patients up to 18 years of age with MPS II who received weekly intravenous tividenofusp alfa for 24 weeks, followed by an 80 week safety extension and 157 week open-label extension.
At the 24-week primary analysis, all patients reported at least one adverse event that emerged during the treatment period. The most common treatment-emergent adverse events were infusion-related reactions, with pyrexia, urticaria, and vomiting being the most frequently reported symptoms, occurring in more than 40% of the participants despite routine premedication. Three participants had serious treatment-related adverse events, however, all continued to receive treatment. Across all study periods, adverse events remained common.
Cerebrospinal fluid levels were observed to be reduced by 91% from baseline, and urinary heparan sulfate levels by 88%. Reductions in heparan sulfate levels appeared to be maintained through week 153, adaptive behavior stabilized or improved, and liver volumes normalized or remained normal.
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To learn more about MPS II and other rare lysosomal disorders, visit https://checkrare.com/diseases/lysosomal-storage-disorders/
