RhGUS: Phase III data

Top-line data from a double-blind, crossover, U.S. Phase III trial in 12 patients ages 5-35 with MPS VII showed that 4 mg/kg IV UX003 every other week for 24-48 weeks met the primary endpoint of reducing urinary GAG excretion after 24 weeks compared to baseline (reduction of 64.8%, p<0.0001). Patients received UX003 or started on placebo and crossed over to treatment with UX003 at 8, 16 or 24 weeks. UX003 missed the secondary endpoint of improving mean MDRI score at 24 weeks compared to baseline (improvement of 0.5 points, p=0.0527). The MDRI endpoint summed scores from a 6-minute walk test (6MWT), forced vital capacity (FVC), shoulder flexion, visual acuity and the Bruininks-Oseretsky Test of Motor Proficiency. For each domain, patients received a score of +1 if they demonstrated improvement to a level at or above a predefined minimally important difference; a score of -1 for worsening to a level at or above the minimally important difference; and a score of 0 for any change to a level less than the minimally important difference. Ultragenyx said UX003 led to a >=1 point improvement in MDRI in 6 patients and no worsening of disease in 5 patients.

In 9 patients who had any change from baseline in 6MWT, UX003 improved 6MWT at 24 weeks by 20.8 meters compared to baseline. Ultragenyx said 3 patients showed minimally important differences in 6MWT at 24 weeks with improvements of 65, 80 and 83 meters, respectively, compared to baseline. Additionally, UX003 led to improvements in fatigue scores to a level at or above the minimally important difference after 24 weeks in 4 patients. All patients experienced treatment-emergent adverse events, including a grade 3 infusion-related reaction that resulted from an infusion rate error. Data were presented at the International Symposium on MPS and Related Diseases in Bonn. ...