NEO1 and NEO-EXT Studies: Long-Term Safety and Exploratory Efficacy of Repeat Avalglucosidase Alfa Dosing for 5.5 Years in Late-Onset Pompe Disease Patients (695)

Objective: To evaluate long-term effects of avalglucosidase alfa in late-onset Pompe disease patients in NEO-EXT (NCT02032524), an ongoing extension of NEO1 (NCT01898364). Background: NEO1 included 24 patients either naive to enzyme replacement therapy (Naive, n=10) or who received ≥9 months’ alglucosidase alfa (Switch, n=14). NEO1 patients received avalglucosidase alfa at 5, 10, or 20 mg/kg qow for 6 months. Design/Methods: After completing NEO1, 19 patients entered NEO-EXT (8 Naive; 11 Switch), initially continuing their NEO1 dose; during 2016, all patients transitioned to 20 mg/kg qow. Results: Patients’ mean (range) ages at NEO1 enrollment were: Naive: 44.8 (20–78) years; Switch: 46.7 (21–68) years. As of July, 2019, 17 patients (7 Naive, 10 Switch) were participating in NEO-EXT and, due to sequential enrollment, had data available up to 5.5 years (2 discontinued for personal reasons). Here we focus on exploratory efficacy data up to Week 260. Forced vital capacity (FVC) % predicted was generally stable in both groups at Week 260 compared with baseline; mean±SD change from baseline for 5, 10, and 20 mg/kg, respectively: Naive: −0.9±12.5; 13.0±not calculable (NC); 7.0±2.6 (Week 234); Switch: −6.5±2.7; −5.8±8.5; 0.2±4.9. Maximum inspiratory/expiratory pressures had similar trends. At Week 260, compared with baseline, 6-minute walk test (6MWT) distance (m) generally remained stable; mean±SD change from baseline for 5, 10, and 20 mg/kg, respectively: Naive: −34.7±15.6; 2.0±NC; 53.5±41.7 (Week 234); Switch: −45.7±86.9; −11.7±83.5; −68.3±151.1. Generally, 6MWT improvement was observed in Naive and Switch patients aged ≤50 years at study start. Avalglucosidase alfa was generally well-tolerated, and the safety profile observed in NEO-EXT was consistent with NEO1. One treatment-naive patient discontinued NEO1 for a study drug-related serious adverse event (SAE; respiratory distress/chest discomfort); no deaths/life-threatening SAEs have occurred. Conclusions: After up to 5.5 years of avalglucosidase alfa treatment, patients in both groups had sustained benefit on pulmonary function and 6MWT. Funding: Sanofi Genzyme. Disclosure: Dr. Dimachkie has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Dimachkie recently served as a consultant or on the speaker’s bureau for Alnylam, ArgenX, Audentes, CSL-Behring, Sanofi Genzyme, Momenta, NuFactor, RMS Medical, Shire Takeda and Terumo.. Dr. Dimachkie has received research support from Dr. Dimachkie received grants from Alexion, Alnylam Pharmaceuticals, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, CSL-Behring, FDA/OPD, GlaxoSmithKline, Genentech, Grifols, MDA, NIH, Novartis, Genzyme, Octapharma, Orphazyme, UCB Biopharma, Viromed an.Dr. Barohn has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with NuFactor and Momenta Pharmaceutical. Dr. Barohn has received research support from PTC Therapeutics, Ra Pharma, Orphazyme, Sanofi Genzyme, FDA OOPD, NIH, and PCORI. Dr. Byrne has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer, Inc.. Dr. Byrne has received royalty, license fees, or contractual rights payments from University of Florida. Dr. Goker-Alpan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amicus, Takeda, BioMarin, and Sanofi Genzyme. Dr. Goker-Alpan has received research support from Amicus, Takeda, Sanofi, Genentech, Protalix, Sangamo, and Freeline. Dr. Kishnani has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi Genzyme, Amicus Therapeutics, Vertex Pharmaceuticals, Asklepios Biopharmaceutical, Inc.. Dr. Kishnani has received compensation for serving on the Board of Directors of Amicus Therapeutics, Pompe and Gaucher Disease Registry Advisory Board, Baebies. Dr. Kishnani holds stock and/or stock options in Asklepios Biopharmaceutical, Inc. (AskBio) which sponsored research in which Dr. Kishnani was involved as an investigator. Dr. Kishnani has received research support from Sanofi Genzyme, Valerion Therapeutics, Amicus Therapeutics. Dr. Wymer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amylyx. Dr. Laforet has received research support from Sanofi Genzyme. Dr. Mengel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Sanofi, Shire, Orphazyme. Dr. Mengel has received research support from Shire, Orphazyme, Sanofi. Dr. Pena has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Inc.. Dr. Pena has received research support from AveXis, Inc., Biogen, Roivant, and Sanofi-Genzyme. Dr. Sacconi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Biomarin, Sanofi Genzyme, Alnylam Pharmaceuticals, AFM, Spark Therapeutic, Biotechspert. Dr. Straub has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Exonics Therapeutics, Roche, Sarepta Therapeutics, and Wave Therapeutics. Dr. Straub has received research support from Sanofi Genzyme, Ultragenyx. Dr. Trivedi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CSL Behring. Dr. Trivedi has received research support from Sanofi. Dr. Van Damme has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Cytokinetics, CSL Behring, Pfizer, Biogen. Dr. Van Der Ploeg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ans. T. van der Ploeg provided consulting services, participated in advisory board meetings and received grants for pre-marketing studies and research from industries (e.g. Sanofi Genzyme, Biomarin, Amicus etc.) via agreements between Erasmus MC and the i. Dr. Van Der Ploeg has received research support from Ans. T. van der Ploeg provided consulting services, participated in advisory board meetings and received grants for pre-marketing studies and research from industries (e.g. Sanofi Genzyme, Biomarin, Amicus etc.) via agreements between Erasmus MC and the i. Dr. Vissing has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Santhera Pharmaceuticals, Audentes Therapeutics, Sanofi/Genzyme, Sarepta Therapeutics, Novartis. Dr. Young has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi Genzyme, Biomarin, UCB, Lowenstein Medical, Medice, Vanda, Biogen. Dr. an Haack has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi Genzyme (Self). Employee of Sanofi Genzyme (Partner). Dr. Fleurinck has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Ablynx, A Sanofi Company. Dr. Johnson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi Genzyme. Dr. Liu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi Genzyme. Dr. Schoser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Audentes, Amicus, Nexien, Lupin, Sanofi-Genzyme. Dr. Schoser has received research support from Greenovation Biopharm, Sanofi-Genzyme, Amicus.