Sanofi Genzyme Presents Results from Phase 1/2 Study of Second-Generation Therapy
Study Design
The NEO1 study was an open-label, multicenter, multinational, ascending dose study of safety, tolerability, pharmacokinetics, pharmacodynamics and exploratory efficacy of investigational neoGAA in treatment-na?ve and alglucosidase alfa-treated (treatment-experienced) late-onset Pompe disease patients. Adult patients with acid ALPHA-glucosidase enzyme deficiency who could walk >=50 m independently without stopping and had upright forced vital capacity (FVC) >=50% predicted at baseline received intravenous infusion neoGAA (5, 10 or 20 mg/kg every other week) for 24 weeks. In the treatment-na?ve group, 9 of 10 treated patients completed the study. In the treatment-experienced patient group, 12 of 14 treated patients completed the study.
Safety Data
NeoGAA was generally safe and well tolerated at all dose levels. There were no deaths or life-threatening serious adverse events (SAEs). One patient experienced a study drug related SAE of respiratory distress and chest discomfort and discontinued treatment. Two additional patients withdrew consent for non-AE related reasons. Overall, 8 of 10 patients (80.0%) in the treatment-na?ve group and 12 of 14 patients (85.7%) in the treatment-experienced group had at least one treatment-emergent AE during the study. The majority of treatment-emergent AEs were non-serious, mild to moderate in intensity and assessed as unrelated to study drug. The most frequently reported treatment-emergent AEs considered related to study drug were myalgia or muscle pain (7 events in 2 patients), headache (3 events in 2 patients) and fatigue (3 events in 3 patients).
Exploratory Efficacy
No clear response relationship was observed between dose levels or treatment groups. At the highest dose tested, 20 mg/kg, which is the dose that will be used in the Phase 3 clinical trial, percent predicted FVC, maximal expiratory pressure (MEP) and maximal inspiratory pressure (MIP) increased by means (± SD) of 6.2 ± 3.2%, 12.0 ± 4.1%, and 7.9 ± 15.7%, respectively, from baseline to Week 25 in treatment-na?ve patients; corresponding changes in treatment-experienced patients were 1.4 ± 5.7%, 6.0± 21.8%, and -0.2 ± 6.9%. After 24 weeks of treatment with the 20 mg/kg dose, the 6-minute walk test distance increased by 24.3 ± 23.0 m in treatment-na?ve patients and decreased by 6.2 ± 64.3 m in treatment-experienced patients.
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