Cipaglucosidase alfa + miglustat in late-onset Pompe disease: two non-ambulatory patients switching from high-dose, high-frequency alglucosidase alfa

Topic:

Clinical Management

Poster Number: P330

Author(s):

Barry Byrne, MD, PhD, University of Florida, Jeffrey Castelli, PhD, Amicus Therapeutics, Inc., Princeton, NJ, USA, Vipul Jain, MS, MBA, Amicus Therapeutics, Inc., Princeton, NJ, USA, Sheela Sitaraman Das, PhD, Amicus Therapeutics, Inc., Princeton, NJ, USA, Jennifer Zhang, MD, Amicus Therapeutics, Inc., Princeton, NJ, USA

Late-onset Pompe disease (LOPD) is a rare, heterogeneous disorder characterized by progressive loss of muscle and respiratory function. An open-label, Phase I/II study (ATB200-02; NCT02675465) evaluated the safety and long-term efficacy of cipaglucosidase alfa plus miglustat (cipa+mig; a two-component therapy for LOPD). As data are limited in non-ambulatory patients or those switching from high-dose, high-frequency (40 mg/kg every week) alglucosidase alfa (alg) to cipa+mig, we analyzed outcomes in two non-ambulatory participants of ATB200-02 aged 18–25 years (Patient 1, female; Patient 2, male). Both received alg for >7 years (including >2 years high dose, high frequency) before entering ATB200-02 and switching to cipa+mig (20 mg/kg + 260 mg every 2 weeks). Outcomes up to 78 months post-baseline were available. In both patients, upper-body quantitative muscle test scores showed marked increases from baseline over the first 12 months, with further improvements up to 54 months (Patients 1 and 2: 42.5 and 17.7 kg at 54 months vs 7.7 and 0 kg at baseline). Subject and Physician Global Impression of Change scores were improved at 6 months and maintained throughout follow-up. The severity of fatigue was above baseline at 6 months, then improved versus baseline at all assessments at 12–72 months. Rotterdam Handicap Scale scores fluctuated over time, with broad similarity versus baseline at 36–78 months in Patient 1, and initial improvement versus baseline followed by a decline at 54–72 months in Patient 2. In both patients, levels of disease biomarkers urine hexose tetrasaccharide and serum creatine kinase were decreased versus baseline at every post-baseline assessment. Eleven non-serious adverse events were reported in the two patients; none were infusion-associated reactions. These two non-ambulatory adults living with LOPD showed sustained, long-term benefits in multiple outcomes, providing evidence for clinicians considering a transition from high-dose, high-frequency alg to cipa+mig. Supported by Amicus Therapeutics, Inc.