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Published on 4 November 2010

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Study success for type 1 Gaucher disease

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Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today presented positive new data from a Phase III clinical trial (study 039) designed to evaluate the efficacy of VPRIV® (velaglucerase alfa for injection) compared with imiglucerase in patients with type 1 Gaucher disease at the 2010 Annual American Society of Human Genetics (ASHG) in Washington D.C.

The study met its primary endpoint and adds to the growing body of clinical evidence which supports the use of VPRIV in patients who have transitioned from imiglucerase or who are treatment-naïve.

In the 039 (head-to-head) study, adult and pediatric patients with type 1 Gaucher disease were included in a nine-month, global, randomised, double-blind, non-inferiority study comparing VPRIV with imiglucerase in treatment-naïve patients aged under two years, with anemia and either thrombocytopenia or organomegaly.

Patients were randomised in a 1:1 ratio to receive either VPRIV or imiglucerase at a dose of 60U/kg via continuous infusion over one hour every other week for 39 weeks (total of 20 infusions per patient).

Thirty-five patients in nine countries were randomised and 34 received the study drug (intent-to-treat [ITT] population was 17 in both the VPRIV and imiglucerase groups). The per-protocol (PP) analysis included 15 patients in each group. Baseline clinical characteristics were generally similar between the two groups, although haemoglobin concentrations appeared slightly higher in the VPRIV group.

After nine months of treatment, haemoglobin concentration improved in both groups. The estimated mean treatment difference for haemoglobin concentration from baseline between patients treated with VPRIV and imiglucerase was 0.14 and 0.16 g/dL in the ITT and PP populations, respectively, with a lower bound of the 97.5% one-sided confidence interval of –0.60 g/dL in both populations, greater than the pre-defined non-inferiority margin of –1.0 g/dL. These results indicate that the primary endpoint was met. Both the VPRIV and imiglucerase groups showed substantial improvements in the secondary endpoints, including platelet counts, spleen volume, liver volume, and plasma biomarkers with no statistically significant difference demonstrated between the treatment groups. The majority of adverse events were mild or moderate in severity.

Shire also reported important findings that suggested substantial antigenic differences when antibody response to treatment with VPRIV and imiglucerase were compared. No patient treated with VPRIV developed anti-drug antibodies while four patients in the imiglucerase group developed antibodies to imiglucerase. Of these four imiglucerase treated patients, one patient had antibodies that inhibited enzyme activity in vitro and enzyme uptake in a cell-based assay. Three patients had antibodies that did not inhibit enzyme activity or uptake.

Data from the Phase III clinical trial extension were also presented at ASHG. In the six month extension study patients from study 034 with type 1 Gaucher disease previously treated with imiglucerase, successfully transitioned to VPRIV and maintained haematological parameters at therapeutic levels through 18 months of continuous treatment. VPRIV was generally well tolerated, and appeared to show a favourable immunogenicity profile.

“For physicians, drug safety is a major consideration; the reported lack of antibodies to infused velaglucerase alfa in these studies, both in naïve and switch patients, is re-assuring to patients and their physicians alike,” said Gregory M. Pastores MD, Associate Professor of Neurology and Pediatrics at the NYU School of Medicine in New York.



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