2023 American Academy of Neurology Abstract Website

Tahseen Mozaffar¹, Benedikt Schoser², Priya Kishnani³, Drago Bratkovic⁴, Paula R. Clemens⁵, Ozlem Goker-Alpan⁶, Xue Ming⁷, Mark Roberts⁸, Kumaraswamy Sivakumar⁹, Ans Van Der Ploeg¹⁰, Mitchell Goldman¹¹, Jacquelyn Wright¹¹, Fred Holdbrook¹¹, Vipul Jain¹¹, Sheela Sitaraman¹¹, Yasmine Wasfi¹¹, Barry Byrne¹²
¹University of California, Irvine, ²Friedrich-Baur-Institut, Neurologische Klinik, Ludwig-Maximilians-Universität München, ³Duke University Medical Center, ⁴PARC Research Clinic, Royal Adelaide Hospital, ⁵Department of Neurology, University of Pittsburgh School of Medicine, Division Chief, Neurology, Medical Service Line, VA Pittsburgh Healthcare System, ⁶Lysosomal and Rare Disorders Research and Treatment Center, ⁷Department of Neurology, Rutgers New Jersey Medical School, ⁸Salford Royal NHS Foundation Trust, ⁹Neuromuscular Clinic and Research Center, ¹⁰Erasmus MC University Medical Center, ¹¹Amicus Therapeutics, Inc., ¹²University of Florida

Objective:

The ongoing ATB200-02 (NCT02675465), open-label, Phase I/II clinical trial aims to evaluate the long-term efficacy and safety of cipaglucosidase alfa/miglustat in adults with Pompe disease.

Background:

Cipaglucosidase alfa/miglustat is an investigational, two-component therapy for Pompe disease. We report data up to 48 months for 6‑minute walk distance (6MWD) and % predicted sitting forced vital capacity (FVC) for ATB200‑02.

Design/Methods:

Three adult ambulatory cohorts - two enzyme replacement therapy (ERT)-experienced (2–6 years [n=11] and ≥7 years [n=6]) and one ERT-naïve (n=6) - received 20 mg/kg intravenous-infused cipaglucosidase alfa plus 260 mg miglustat orally biweekly in an ongoing study. Changes from baseline (CFBL) in multiple endpoints were assessed at intervals. We report data from 6, 12, 24, 36 and 48 months.

Results:

Baseline characteristics represented the Pompe disease population. Durable improvements occurred at 6, 12, 24, 36 and 48 months in 6MWD (m): pooled analyses of ERT-experienced cohorts, mean(±SD) CFBL: 23.1(±44.75), n=16; 33.5(±49.62), n=16; 25.2(±63.30), n=13; 9.8(±85.98), n=12; 20.7(±101.84), n=9, respectively; ERT-naïve cohort: 36.7(±29.08), n=6; 57.0(±29.96), n=6; 54.4(±36.18), n=6; 43.5(±45.19), n=5; 52.2(±46.59), n=4, respectively. FVC (%) was stable or improved in ERT-experienced cohorts, mean(±SD) CFBL: −0.9(±8.59), n=16; −1.2(±5.95), n=16; 1.0(±7.96), n=13; −0.3(±6.68), n=10; 1.0(±6.42), n=6, respectively, and improved in the ERT-naïve cohort: 4.2(±5.04), n=6; 3.2(±8.42), n=6; 4.7(±5.09), n=6; 6.2(±3.35), n=5; 8.3(±4.50), n=4, respectively. Over 48 months, serum CK and urine Hex4 biomarkers improved in ERT-experienced and ERT-naïve cohorts.

Conclusions:

In ATB200-02, ERT-experienced cohorts had durable mean improvements (CFBL) in motor function that were sustained up to 48 months of follow-up; respiratory function was stable and maintained over the same period. TheERT-naïve cohort showed durable mean improvements (CFBL) in motor and respiratory function that were sustained up to 48 months of follow-up. Biomarker outcomes were consistent with other efficacy results. The overall safety profile for ambulatory cohorts was similar to approved ERT. Supported by Amicus Therapeutics, Inc.