Long-term follow-up of cipaglucosidase alfa/miglustat in ambulatory patients with Pompe disease: an open-label Phase I/II study (ATB200-02)


Clinical Trials

Poster Number: 92


Barry Byrne, MD, PhD, University of Florida, Benedikt Schoser, MD, PhD, Friedrich-Baur-Institut, Ludwig-Maximilians-Universität München, Munich, Germany, Priya Kishnani, MD, Duke University Medical Center, Durham, NC, USA, Drago Bratkovic, MD, PARC Research Clinic, Royal Adelaide Hospital, Adelaide, SA, Australia, Paula R. Clemens, MD, University of Pittsburgh School of Medicine, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA, Ozlem Goker-Alpan, MD, Lysosomal and Rare Disorders Research and Treatment Center, Fairfax, VA, USA, Xue Ming, MD, PhD, Neurology, Rutgers New Jersey Medical School, Newark, NJ, USA, Mark Roberts, MD, PhD, Salford Royal NHS Foundation Trust, Salford, UK, Matthias Vorgerd, MD PhD, University Hospital Bergmannsheil, Heimer Institute for Muscle Research, Bochum, Germany, Kumaraswamy Sivakumar, MD, Neuromuscular Clinic and Research Center, Phoenix, AZ, USA, Ans T. van der Ploeg, MD, PhD, Erasmus MC University Medical Center, Rotterdam, Netherlands, Mitchell Goldman, MD, PhD, Amicus Therapeutics, Inc., Philadelphia, PA, USA, Jacquelyn Wright, MS, Amicus Therapeutics, Inc., Philadelphia, PA, USA, Fred Holdbrook, PhD, Amicus Therapeutics, Inc., Philadelphia, PA, USA, Vipul Jain, MS, Amicus Therapeutics, Inc., Philadelphia, PA, USA, Sheela Sitaraman, PhD, Amicus Therapeutics, Inc., Philadelphia, PA, USA, Yasmine Wasfi, MD, PhD, Amicus Therapeutics, Inc., Philadelphia, PA, USA, Tahseen Mozaffar, MD, University of California, Irvine, CA, USA

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.