Long-term Follow-up of Cipaglucosidase Alfa/Miglustat in Ambulatory Patients with Pompe Disease: An Open-label Phase I/II Study (ATB200-02) (S48.007) (2023)

<h3>Objective:</h3> 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. <h3>Background:</h3> 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. <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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. <h3>Conclusions:</h3> 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. The ERT-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. <b>Disclosure:</b> Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Modis Therapeutics. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB/ Ra Pharmaceuticals. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Maze Therapeutics. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark Therapeutics. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for National Institutes of Health. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Argenx. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Neuromuscular Disease Foundation. The institution of Dr. Mozaffar has received research support from NIH. The institution of Dr. Mozaffar has received research support from Muscular Dystrophy Association. The institution of Dr. Mozaffar has received research support from Sanofi-Genzyme. The institution of Dr. Mozaffar has received research support from Argenx. The institution of Dr. Mozaffar has received research support from Amicus Therapeutics. The institution of Dr. Mozaffar has received research support from Spark Therapeutics. The institution of Dr. Mozaffar has received research support from Audentes Therapeutics. The institution of Dr. Mozaffar has received research support from Cartesian. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Benedikt Schoser, 18260 has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi Genzyme. Benedikt Schoser, 18260 has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofo Genzyme. Benedikt Schoser, 18260 has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Nexien. Benedikt Schoser, 18260 has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. Benedikt Schoser, 18260 has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Audentes. Benedikt Schoser, 18260 has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Kedrion. Benedikt Schoser, 18260 has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Lupin. Benedikt Schoser, 18260 has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Argenc. Benedikt Schoser, 18260 has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Spark. Priya Kishnani, MD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi/Genzyme. Priya Kishnani, MD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amicus Therapeutics. Priya Kishnani, MD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Maze Therapeutics. Priya Kishnani, MD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for JCR Pharmaceutical. Priya Kishnani, MD has received personal compensation in the range of $500,000-$999,999 for serving as a Consultant for Asklepios Biopharmaceutical Inc. (AskBio). Priya Kishnani, MD has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. Priya Kishnani, MD has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus Therapeutics. Priya Kishnani, MD has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Baebies, Inc.. The institution of Priya Kishnani, MD has received research support from Sanofi/Genzyme. Priya Kishnani, MD has received research support from Amicus Therapeutics. Priya Kishnani, MD has received intellectual property interests from a discovery or technology relating to health care. Priya Kishnani, MD has received intellectual property interests from a discovery or technology relating to health care. Drago Bratkovic has nothing to disclose. The institution of Dr. Clemens has received research support from NS Pharma. The institution of Dr. Clemens has received research support from ReveraGen. The institution of Dr. Clemens has received research support from Amicus. The institution of Dr. Clemens has received research support from Sanofi. The institution of Dr. Clemens has received research support from Spark. The institution of Dr. Clemens has received research support from NIH. The institution of Dr. Clemens has received research support from MDA. The institution of Dr. Clemens has received research support from FDA. Ozlem Goker-Alpan has nothing to disclose. Dr. Ming has nothing to disclose. Mark Roberts has nothing to disclose. Dr. Sivakumar has nothing to disclose. The institution of Ans Van Der Ploeg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme . The institution of Ans Van Der Ploeg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. The institution of Ans Van Der Ploeg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark Therapeutics . The institution of Ans Van Der Ploeg has received research support from Sanofi Genzyme. Dr. Goldman has received personal compensation for serving as an employee of Amicus. Dr. Goldman has received stock or an ownership interest from Amicus. Jacquelyn Wright has received personal compensation for serving as an employee of Amicus Therapeutics. Frederick Holdbrook has received personal compensation for serving as an employee of Amicus Therapeutics Inc.. Frederick Holdbrook has stock in Amicus Therapeutics Inc.. Mr. Jain has nothing to disclose. Sheela Sitaraman has nothing to disclose. Dr. Wasfi has received personal compensation for serving as an employee of Amicus Therapeutics. Dr. Wasfi has stock in Amicus Therapeutics. Barry Byrne has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for AavantiBio. Barry Byrne has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Barry Byrne has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex. Barry Byrne has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Barry Byrne has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Muscular Dystrophy Association. Barry Byrne has received intellectual property interests from a discovery or technology relating to health care.