NEO1 and NEO-EXT studies: Long-term safety of repeat avalglucosidase alfa dosing for 4.5 years in late-onset Pompe disease patients

Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat avalglucosidase alfa dosing (5, 10, or 20 mg/kg qow) for 6 months were evaluated in NEO1 (NCT01898364) in late-onset Pompe disease patients either treatment-naïve (Naïve) or having received alglucosidase alfa for ≥9 months (Switch). In NEO-EXT (NCT02032524), an ongoing NEO1 extension, long-term safety and pharmacokinetics of repeat avalglucosidase alfa dosing will be monitored over 6 years. Interim safety results after 4.5 years of NEO-EXT are reported here. Mean ages at NEO1 enrollment were: Naïve: 44.8 (SD:20.3, range:20-78) years and Switch: 46.7 (SD:14.1, range:21-68) years. Of the 24 NEO1 participants, 19 entered NEO-EXT (8/10 Naïve 11/14 Switch) 17 are currently participating (7/8 Naïve 10/11 Switch) 2 participants discontinued NEO-EXT (personal reasons). During 2016, all NEO-EXT participants switched to avalglucosidase alfa 20 mg/kg qow. By May 2018, total infusions reached 731 (Naïve) and 1174 (Switch) mean infusions were Naïve: 73 (SD:43, range:9-113) and Switch: 84 (SD:40, range:8-118). Mean avalglucosidase alfa exposure duration reached 1025 (SD:611, range:109-1572) days for Naïve and 1179 (SD:570, range:102-1658) days for Switch participants. Treatment-emergent adverse events (AEs) were generally mild across doses. Most frequently reported treatment-related AEs were nausea, fatigue, and headache (3 participants each) and dizziness, dyspnea, erythema, myalgia, muscle spasms, and rash (2 participants each) and are unchanged since the last safety update (WORLDSymposium™ 2018). One Switch participant discontinued NEO1 for a study drug-related serious AE (respiratory distress/chest discomfort) no deaths/life-threatening serious AEs have occurred. Anti-avalglucosidase IgG/IgM antibodies developed in 9/10 Switch (median titer:1600, range:200-51,200) and 9/14 Naïve (median titer:400, range:50-12,800) participants. No patient developed IgE antibodies or tested positive for enzyme activity inhibition. In NEO-EXT, the avalglucosidase alfa safety profile is consistent with the initial 6 months’ treatment during NEO1, with no additional participants developing anti-avalglucosidase alfa IgG/IgM antibodies or new allergic reactions. Funding: Sanofi Genzyme.