FP.17 Long-term follow-up of cipaglucosidase alfa/miglustat in ambulatory patients with Pompe disease: An open-label phase I/II study (ATB200-02)

Abstract

Cipaglucosidase alfa/miglustat is an investigational, two-component therapy (cipaglucosidase alfa: novel recombinant human GAA; miglustat: enzyme stabiliser) being studied in patients Pompe disease. We report data for up to 36 months for 6-minute walk distance (6MWD) and % predicted sitting forced vital capacity (FVC) from ATB200-02 (NCT02675465). Our ongoing study enrolled 3 cohorts of ambulatory patients: 2–6 years (n=11; age 18–65 years) or ≥7 years (n=6; age 18–75 years) prior enzyme replacement therapy (ERT) with 20 mg/kg alglucosidase alfa biweekly, and ERT naïve (n=6; age 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. Baseline characteristics were representative of the Pompe population. At 6, 12, 24 and 36 months, durable improvements in 6MWD (metres) were seen: integrated analyses of ERT-experienced cohorts, mean(±standard deviation [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 mostly 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 for cipaglucosidase alfa/miglustat was similar to that of approved ERT. In conclusion, most ERT-experienced patients either improved or stabilised in efficacy and biomarker outcomes. ERT-naïve patients showed clinical benefit with cipaglucosidase alfa/miglustat. Overall, improvements in clinical response up to 36 months follow-up were sustained and durable.