The safety and efficacy of Vimizim were assessed in a 24-week, randomized, double-blind, placebo-controlled clinical trial of 176 patients with MPS IVA. The age of patients ranged from 5 to 57 years. The majority of the patients (82%) presented with a medical history of musculoskeletal conditions, which includes knee deformity (52%), kyphosis (31%), hip dysplasia (22%), prior spinal fusion surgery (22%) and arthralgia (20%). At baseline, all enrolled patients could walk more than 30 meters (m) but less than 325 m in six minutes.
Patients received Vimizim 2 mg/kg once per week (n=58), Vimizim 2 mg/kg once every other week (n=59), or placebo (n=59).
The primary endpoint was the change from baseline in the distance walked in six minutes (six minute walk test, 6-MWT) at Week 24. The other endpoints included changes from baseline in the rate of stair climbing in three minutes (three-minute stair climb test, 3-MSCT) and changes from baseline in urine KS levels at Week 24. The treatment effect in the distance walked in 6 minutes, compared to placebo, was 22.5 m (CI95, 4.0, 40.9; p=0.0174) in patients who received Vimizim 2 mg/kg once per week. There was no difference in the rate of stair climbing between patients who received Vimizim 2 mg/kg once per week and those who received placebo. Patients who received Vimizim 2 mg/kg once every other week performed similarly in the 6-MWT and 3-MSCT as those who received placebo. The reduction in urinary KS levels from baseline, a measure of pharmacodynamic effect, was greater in the Vimizim treatment groups compared to placebo. The relationship between urinary KS and other measures of clinical response has not been established.
Table 3: Results from Placebo-Controlled Clinical Trial
* One patient in the Vimizim group dropped out after 1 infusion
† Observed Vimizim mean change – Placebo mean change
‡ ANCOVA Model-based Vimizim mean change – Placebo mean change, adjusted for baseline 6MWT categories (less than or equal to 200 meters, greater than 200 meters) and age groups (5-11, 12-18, 19 or older)
§ p-value based on the model-based difference in means
Extension Trial
Patients who participated in the placebo-controlled trial were eligible to continue treatment in an open-label extension trial. One hundred seventy-three of 176 patients enrolled in the extension trial in which patients received Vimizim 2 mg/kg once per week (n=86) or Vimizim 2 mg/kg once every other week (n=87). In patients who continued to receive Vimizim 2 mg/kg once per week for another 48 weeks (for a total of 72-week exposure), walking ability showed no further improvement beyond the first 24 weeks of treatment in the placebo-controlled trial.
Close VIMIZIM (Elosulfase Alfa) Injection, Solution, Concentrate [BioMarin Pharmaceutical Inc.]
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