Phase 1 Exploratory Efficacy of the Novel Enzyme Replacement Therapy NeoGAA in Treatment-Naïve and Alglucosidase Alfa-Treated Late-Onset Pompe Disease Patients (I4.011)

OBJECTIVE: This open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and exploratory efficacy of the second-generation enzyme replacement therapy neoGAA in 10 treatment-naive and 14 alglucosidase alfa-experienced (≥9 mo of treatment) patients with late-onset Pompe disease.BACKGROUND: Exploratory efficacy results are presented here; safety profile and pharmacokinetics are reported separately.DESIGN/METHODS: Adult patients who could walk ≥50 m independently and had upright FVC ≥50[percnt] predicted at baseline received IV neoGAA (5, 10, or 20mg/kg qow) for 24 wks.RESULTS: Study completers included 9 treatment-naive patients (5mg/kg, n=3; 10mg/kg, n=3; 20mg/kg, n=3) and 12 treatment-experienced patients (5mg/kg, n=3; 10mg/kg, n=4; 20mg/kg, n=5). NeoGAA was well-tolerated in both groups. Quadriceps muscle biopsy glycogen levels were low (~6[percnt]) in most patients in both groups at baseline, and remained mostly unchanged. Naive patients’ percent predicted sitting-FVC remained stable or increased from baseline to Week 25 (mean±SD changes: 5mg/kg, −2.7±8.8[percnt], n=4; 10mg/kg, +4.3±4.9[percnt], n=3; 20mg/kg, +6.2±3.2[percnt], n=3), while MEP and MIP [percnt] predicted improved or remained stable (respective mean ± SD changes: 5mg/kg,+8.1±2.8[percnt], n=2, +6.1±0.79[percnt], n=2; 10mg/kg, 16.5±8.0[percnt], n=3, 10.6±4.9[percnt], n=3;20mg/kg, 12.0±4.1[percnt], n=3; 7.9 ±15.7[percnt], n=3). In treatment-experienced patients, [percnt] predicted sitting-FVC remained stable from baseline to week 25 (5mg/kg, −0.5±4.3[percnt], n=4; 10mg/kg, −2.0±2.2[percnt], n=4; 20mg/kg, +1.4±5.7[percnt], n=5), as did [percnt] predicted MEP and MIP (5mg/kg, −3.5±10.8[percnt], n=4, +10.5±7.3[percnt], n=4; 10 g/kg, +15.7±38.4[percnt], n=3, +4.2±12.6[percnt], n=3; 20mg/kg, +6.0±21.8[percnt], n=5; −0.2±6.9[percnt], n=5). Six minute walk test distances were generally stable or increased with neoGAA without relationship to patient group or dose level. QMFT and HHD scores improved in both groups, irrespective of dose, whereas GSGC and GMFM-88 showed minimal changes across groups and all dose levels.CONCLUSIONS: While the efficacy assessments were exploratory, these results support further development of neoGAA. Study Supported by: Genzyme, a Sanofi Company Disclosure: Dr. Pena has received personal compensation for activities with Sanofi-Genzyme as an advisory board member. Dr. Barohn has received personal compensation for activities with Grifols u0026 Genzyme, Speakers Bureau, NuFactor as speaker and consultant. Dr. Byrne has nothing to disclose. Dr. Desnuelle has nothing to disclose. Dr. Goker-Alpan has received personal compensation for activities with Genzyme, Shire HGT, Actelion, and Biomarin. Dr. Ladha has received personal compensation for activities with Genzyme and Biogen as a speaker and/or consultant. Dr. Ladha received a research support from Genentech. Dr. Laforet has received personal compensation for activities with Amicus Therapuetics as an advisory board participant. Dr. Mengel has received personal compensation for activities with Genzyme, Synageva, Orphazyme, Actelion, and Biomarin as a speaker and/or consultant. Dr. Pestronk has received personal compensation for activities with Athena Diagnostics. Dr. Pouget has nothing to disclose. Dr. Schoser has received personal compensation for activities with Genzyme, BioMarin Pharmaceuticals, Audentes Therapeutics, and Amicus Therapeutics. Dr. Straub has received personal compensation for activities with Genzyme, Audentes Therapeutics, Italfarmaco S.p.A., Summit Therapeutics and TrophyNOD as a speaker an advisory board member. Dr. Trivedi has nothing to disclose. Dr. Van Damme has nothing to disclose. Dr. Vissing has received personal compensation for activities with Alexion Pharmaceuticals and Ultragenyx as an advisory board member. Dr. Young has received personal compensation for activities with Genzyme, Biomarin, UCB, Heinen und Lowenstein, and Medice. Dr. Thurberg has received stock grants. Dr. Culm-Merdek has received personal compensation for activities with Genzyme as an employee. Dr. Short holds stock and/or stock options in Sanofi-Aventis Pharmaceuticals, Inc. Dr. Van der Ploeg has received personal compensation for activities with Genzyme Corporation as a consultant.