Shire plc, the global specialty biopharmaceutical company, presented positive data from a phase-III clinical trial (TKT-034) designed to evaluate the safety of switching to VPRIV (velaglucerase alfa for injection), from imiglucerase, as well as an interim analysis of safety data from an ongoing multi-centre open-label treatment protocol (HGT-GCB-058) implemented to provide VPRIV to patients affected by the continuing shortage of imiglucerase. A post-hoc analysis of phase-I/II data on therapeutic goal attainment was also presented at the 2010 American College of Medical Genetics Annual Clinical Genetics Meeting in Albuquerque, New Mexico. These data add to the growing body of clinical evidence which support the use of VPRIV in patients both transitioning from imiglucerase or who are treatment naïve.

Adult and paediatric patients with Type 1 Gaucher disease were switched from imiglucerase (15-60 U/kg every other week) to the same number of units of VPRIV in the Phase III switch study (40 patients) and the ongoing US treatment protocol (>150 patients). In study TKT-034, no patients developed IgG antibodies to VPRIV, including three patients who tested positive for anti-imiglucerase antibodies at screening. In addition, haemoglobin concentration, platelet counts, and liver and spleen volumes remained stable over the course of the one year study, demonstrating safety and maintenance of efficacy over this time frame. One patient in the Phase III trial discontinued due to a serious hypersensitivity reaction and the most common side effects reported in the two studies were infusion-related reactions.

“Results from the phase-III study provide important information regarding the safety and sustained efficacy of VPRIV for patients with Type 1 Gaucher disease who were previously on imiglucerase and should help inform treatment decisions during and after the imiglucerase supply shortage,” said Dr Gregory Grabowski, director of the Division of Human Genetics, Cincinnati Children’s Hospital Medical Center and Principal Investigator of the 034 study. “These data confirm what many physicians have experienced.”

A post hoc analysis from a third study, TKT-025EXT, designed to examine attainment of long-term therapeutic goals in 8 patients with Type 1 Gaucher disease treated with velaglucerase alfa, was also presented at the meeting. The initial dose of 60 U/kg was lowered to 30 U/kg after patients achieved at least 2 of 4 predefined therapeutic goals following one year of treatment. Clinically meaningful achievement of long-term therapeutic goals for haemoglobin concentration, platelet counts, and liver and spleen volumes was observed within four years of initiation of treatment.

Shire also reported important findings that suggested substantial antigenic differences when antibody response to treatment with VPRIV and imiglucerase were compared. Among the 99 patients who enrolled in the phase-III studies the seroconversion rate was 1% (1 of 82) against VPRIV versus 23% (4 of 17) against imiglucerase.

Velaglucerase alfa is manufactured in Shire’s facility in Cambridge, which was inspected and approved by the US FDA for the commercial production of VPRIV.

VPRIV (velaglucerase alfa for injection) was approved by the US FDA as a long-term enzyme replacement therapy for adult and pediatric patients with Type 1 Gaucher disease on February 26, 2010.