Background: Pompe disease is a rare lysosomal storage disorder characterized by progressive loss of muscle/respiratory function due to acid α-glucosidase (GAA) deficiency. Cipaglucosidase alfa/miglustat is an investigational, 2-component therapy (cipaglucosidase alfa: novel recombinant human GAA; miglustat: enzyme stabilizer). We report up to 36 months of assessments for 6-minute walk distance (6MWD) and % predicted sitting forced vital capacity (FVC) from ATB200-02 (NCT02675465).
Methods: This ongoing study enrolled three cohorts of ambulatory patients: 2–6 years (n=11; aged 18–65 years) or ≥7 years (n=6; aged 18–75 years) prior enzyme replacement therapy (ERT) with 20 mg/kg alglucosidase alfa biweekly, ERT-naïve (n=6; aged 18–65 years). Doses were 20 mg/kg cipaglucosidase alfa by intravenous infusion/260 mg miglustat orally biweekly in the long-term extension. Change from baseline (CFBL) in multiple endpoints were assessed at intervals. We report data at 6, 12, 24 and 36 months.
Results: Baseline characteristics were representative of the Pompe disease population. At 6, 12, 24 and 36 months, integrated analyses of ERT-experienced cohorts showed durable improvements in 6MWD (meters), mean(±SD) CFBL: 23.1(±44.75), n=16; 33.5(±49.62), n=16; 21.3(±60.90), n=10; 47.8(±53.80), n=8; respectively; ERT-naïve cohort: 36.7(±29.08), n=6; 57.0(±29.96), n=6; 60.7(±36.52), n=5; 43.5(±45.19), n=5; respectively. FVC (%) was generally stable in ERT-experienced cohorts, mean(±SD) CFBL: –0.8(±8.69), n=16; –1.3(±5.95), n=16; –0.9(±7.65), n=10; –0.4(±7.56), n=8; respectively, but improved in the ERT-naïve cohort: 5.5(±5.68), n=6; 4.5(±7.92), n=6; 6.8(±6.76), n=5; 6.2(±3.42), n=5; respectively. Over 36 months, cipaglucosidase alfa/miglustat was associated with reductions in creatine kinase and urine Hex4. The safety profile of cipaglucosidase alfa/miglustat was similar to approved ERT.
Conclusions: Results from ATB200-02 showed that most ERT-experienced patients either improved or stabilized in their efficacy and biomarker outcomes. ERT-naïve patients demonstrated clinical benefit with cipaglucosidase alfa/miglustat. Overall, there were sustained and durable improvements in clinical response up to 36 months’ follow-up.
Supported by Amicus Therapeutics.