Pharmacokinetics of Alglucosidase Alfa Manufactured at the 4000‐L Scale in Participants with Pompe Disease: A Phase 3/4 Open‐Label Study

Abstract

AbstractPompe disease is a rare, autosomal recessive, degenerative neuromuscular disease caused by deficiency of acid α‐glucosidase, a lysosomal enzyme that degrades α‐1,4 and α‐1,6 linkages in glycogen. The objectives of this study (PAPAYA; NCT01410890) were to (1) characterize the pharmacokinetics of 20 mg/kg body weight alglucosidase alfa manufactured at the 4000‐L scale following a single intravenous dose in participants aged less than 18 and 18 years or older with Pompe disease and (2) evaluate the relationship between anti–alglucosidase alfa antibody titers and the pharmacokinetics of alglucosidase alfa. Mean maximum plasma concentration and area under the concentration–time curve from time zero and extrapolated to infinite time were 204 μg/mL and 1110 μg • h/mL for participants aged less than 18 years (n = 10), respectively, and 307 μg/mL and 1890 μg • h/mL for participants aged 18 years or older (n = 10), respectively. Mean terminal half‐life was 5.43 hours in participants aged less than 18 years with a high variability (70%) and 3.84 hours in participants aged 18 years or older with a low variability (21%). Mean maximum plasma concentration and area under the concentration–time curve from time zero and extrapolated to infinite time were 256 μg/mL and 1452 μg • h/mL, respectively, in anti–alglucosidase alfa–negative participants (n = 12) and 262 μg/mL and 1703 μg • h/mL, respectively, in anti–alglucosidase alfa–positive participants (n = 7). The study findings enrich available data from existing information on alglucosidase alfa without changing its known risks and benefits.