Pharmacokinetics of Novel Plant Cell-Expressed Taliglucerase Alfa in Adult and Pediatric Patients with Gaucher Disease

Abstract

Taliglucerase alfa is a beta-glucocerebrosidase enzyme replacement therapy approved in the United States, Israel, and other countries for treatment of Type 1 Gaucher disease in adults, and is the first approved plant cell—expressed recombinant protein. In this report, taliglucerase alfa pharmacokinetics were assessed in adult and pediatric patients with Gaucher disease from separate multicenter trials of 30 Units/kg and 60 Units/kg doses infused every 2 weeks. Serial blood samples were obtained from adult patients following single-dose administration on day 1 (n = 26) and multiple doses at week 38 (n = 29), and from pediatric patients following administration of multiple doses of taliglucerase alfa for 10–27 months (n = 10). In both adult and pediatric patients, maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time zero to last measureable concentration (AUC0-t), and from time zero to infinity (AUC0-∞) were higher after 60 Units/kg dose than 30 Units/kg dose. No tendency for accumulation or change in taliglucerase alfa pharmacokinetic parameters over time from day 1 to week 38 was observed with repeated doses of 30 or 60 Units/kg in adults. After multiple doses, mean (range) dose-normalized pharmacokinetic parameters were similar for adult versus pediatric patients receiving 60 Units/kg: Cmax expressed in ng/mL/mg was 42.4 (14.5–95.4) in adults and 46.6 (34.4–68.4) in pediatric patients, AUC0 t expressed in ng•h/mL/mg was 63.4 (26.3–156) in adults and 63.9 (39.8–85.1) in pediatric patients, t1/2 expressed in minutes was 34.8 (11.3–104) in adults and 31.5 (18.0–42.9) in pediatric patients and total body clearance expressed in L/h was 19.9 (6.25–37.9) in adults and 17.0 (11.7–24.9) in pediatric patients. These pharmacokinetic data extend the findings of taliglucerase alfa in adult and pediatric patients.Trial RegistrationClinicalTrials.gov. NCT00376168 (in adults); NCT01411228 (in children)

Taliglucerase alfa: safety and efficacy across 6 clinical studies in adults and children with Gaucher disease

“…The characterization of taliglucerase alfa pharmacokinetics (PK) was based on samples from 26 of the 31 patients in the pivotal PB-06-001 study (treatment-naïve adult patients) and 10 of the 15 patients in PB-06-006 (treatment-naïve and treatment-switched paediatric patients) [ 22 ]. Single-dose PK in adults were based on day 1 serial blood samples and multiple-dose PK were based on week 38 samples [ 22 ]. Multiple-dose PK in paediatric patients were based on samples collected after 10 to 27 months of treatment.…”

“…In adults and children, the 60 U/kg dose resulted in higher exposure (as measured by maximum plasma concentration, area under the plasma concentration-versus-time curve from time zero to the last measured concentration, and area under the plasma concentration-versus-time curve from time zero to infinity) than the 30 U/kg dose [ 22 ]. Within the adult and paediatric patient populations, the two dose groups were similar in mean time of maximum plasma concentration and elimination half-life values for taliglucerase alfa [ 22 ]. No tendency for accumulation or change in taliglucerase alfa PK was observed after repeated infusion with either dose over 38 weeks in adult patients [ 22 ].…”

“…Within the adult and paediatric patient populations, the two dose groups were similar in mean time of maximum plasma concentration and elimination half-life values for taliglucerase alfa [ 22 ]. No tendency for accumulation or change in taliglucerase alfa PK was observed after repeated infusion with either dose over 38 weeks in adult patients [ 22 ]. Furthermore, dose-normalized exposure was comparable between adult and paediatric patients and showed dose proportionality in paediatric patients [ 22 ].…”

“…No tendency for accumulation or change in taliglucerase alfa PK was observed after repeated infusion with either dose over 38 weeks in adult patients [ 22 ]. Furthermore, dose-normalized exposure was comparable between adult and paediatric patients and showed dose proportionality in paediatric patients [ 22 ].…”

Estudio de la fisiopatología de las alteraciones óseas asociadas a la enfermedad de Gaucher

“…Comparado con otros órganos como el corazón, el hígado o el riñón, el hueso está menos vascularizado por lo que los medicamentos utilizados para tratar patologías óseas son menos efectivos debido a una baja disponibilidad en el sitio diana (Lin, 1996). Además de esta característica ósea, hay que tener en cuenta que la enzima recombinante tiene una vida media corta en circulación (Abbas et al, 2015;Van Patten et al, 2007). Por lo tanto, no sólo podrían ser útiles las terapias que incrementen la accesibilidad de la enzima al hueso, sino que también se deben estudiar terapias alternativas que puedan ser administradas como coadyuvantes para mejorar la función ósea en estos pacientes.…”