Long-term safety and efficacy of taliglucerase alfa in pediatric patients with Gaucher disease who were treatment-naïve previously treated with immiglucerase

Abstract

CO RR EC TE D P RO OF with type 1 Gaucher disease (GD) in the United States, Israel, Australia, Canada, and other countries, and is approved for treatment of pediatric patients in the United States, Australia, and Canada, and for hematologic manifestations in pediatric patients with type III GD in Canada. Study PB-06-005 was a Phase 3B, multicenter, doubleblind, multiple-dose, randomized trial that examined the safety and efficacy of taliglucerase alfa through 12 months. Treatment-naive patients aged 2 to b18 years with GD requiring enzyme replacement therapy based on clinical condition were randomized to receive either 30 or 60 U/kg of taliglucerase alfa every other week. A total of 11 patients were allocated to taliglucerase alfa (n = 6, taliglucerase alfa 30 U/kg; n = 5, taliglucerase alfa 60 U/kg), were treated, and completed Study PB-06-005. Due to small patient numbers, there were numerical imbalances in disease parameters between the 30-U/kg and 60-U/kg groups at baseline. However, clinically, they were comparable at baseline: Patients in the 2 dose groups had similarly mild anemia, similar risks of bleeding based onplatelet count, andmuch larger than normal organ volumes. Mean percentage changes from baseline were used to compare the response between the dose groups and as a measure of control for numerical imbalances in baseline disease parameters. Results through 12months demonstrated that taliglucerase alfa 30 and 60 U/kg, respectively, increased mean hemoglobin concentration (+13.8% and +15.8%) and mean platelet count (+30.9% and +73.7%), while also reducing mean multiples of normal in spleen volume (−34.1% and−48.5%), multiples of normal in liver volume (−14.5% and −25.0%), chitotriosidase activity (−58.5% and −66.1%), and CCL18 concentration (−50.6% and −52.6%). Although statistical analysis was not possible due to the small numbers of patients, both treatment groups demonstrated clinically meaningful improvement from baseline in these disease parameters with numerically greater improvement observed in the 60-U/kg dose group. The authors wish to acknowledge fellow investigator Dr. Rene Heitner who passed away in January, 2012. This study was sponsored by Protalix BioTherapeutics. Pfizer and Protalix entered into an agreement in November 2009 to develop and commercialize taliglucerase alfa.