Duvoglustat: Preliminary Phase II data

Preliminary data from 16 patients with Pompe's disease in the first 3 cohorts of the open-label, international Phase II Study 010 trial showed that single ascending-doses of oral AT2220 plus enzyme replacement therapy (ERT) with Myozyme/ Lumizyme alglucosidase alfa produced dose-dependent increases in recombinant human GAA activity in plasma samples in all patients. Compared to Myozyme/Lumizyme alone, mean fold-increases in recombinant human GAA activity as measured by plasma area under the curve (AUC) were 1.5 for 50 mg AT2220 plus ERT, 1.7 for 100 mg AT2220 plus ERT and 2 for 250 mg AT2220 plus ERT.

Additionally, Amicus said there was no consistent change observed in recombinant human GAA uptake into muscle tissue for patients receiving low-dose AT2220 plus ERT compared to ERT alone as determined by muscle biopsies on day 7. However, muscles biopsies taken on either day 3 or 7 for patients receiving 100 and 250 mg doses of AT2220 plus ERT suggested that more recombinant human GAA "may be taken up" into muscle tissue compared to ERT alone. AT2220 plus ERT was generally well tolerated with no treatment-related adverse events reported. Additionally, AT2220 was cleared from the muscles to negligible levels by day 7 in all 3 cohorts. The company is enrolling a fourth cohort of patients to receive 600 mg AT2220 plus ERT with data expected by year end. Data were presented at the World Muscle Society meeting in Perth. ...