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

Abstract

Pompe 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.

Keywords: Pompe disease; alglucosidase alfa; clinical study; enzyme replacement therapy; pharmacokinetics.