Drug Discovery & Development - November 04, 2010
Shire plc, the global specialty biopharmaceutical company, presented positive new data from a Phase 3 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 9-month, global, randomized, double-blind, non-inferiority study comparing VPRIV with imiglucerase in treatment-naïve patients aged ≥2 years, with anemia and either thrombocytopenia or organomegaly. Patients were randomized 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). 35 patients in 9 countries were randomized 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 2 groups, although hemoglobin concentrations appeared slightly higher in the VPRIV group.
After 9 months of treatment, hemoglobin concentration improved in both groups. The estimated mean treatment difference for hemoglobin 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 4 patients in the imiglucerase group developed antibodies to imiglucerase. Of these four imiglucerase treated patients, 1 patient had antibodies that inhibited enzyme activity in vitro and enzyme uptake in a cell-based assay. 3 patients had antibodies that did not inhibit enzyme activity or uptake.
Data from the Phase 3 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 hematological 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.
Shire’s VPRIV clinical trial program is the largest and most comprehensive set of Phase 3 trials conducted to date for type 1 Gaucher disease.
Date: November 4, 2010
Source: Shire plc
In the 039 (head-to-head) study, adult and pediatric patients with type 1 Gaucher disease were included in a 9-month, global, randomized, double-blind, non-inferiority study comparing VPRIV with imiglucerase in treatment-naïve patients aged ≥2 years, with anemia and either thrombocytopenia or organomegaly. Patients were randomized 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). 35 patients in 9 countries were randomized 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 2 groups, although hemoglobin concentrations appeared slightly higher in the VPRIV group.
After 9 months of treatment, hemoglobin concentration improved in both groups. The estimated mean treatment difference for hemoglobin 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 4 patients in the imiglucerase group developed antibodies to imiglucerase. Of these four imiglucerase treated patients, 1 patient had antibodies that inhibited enzyme activity in vitro and enzyme uptake in a cell-based assay. 3 patients had antibodies that did not inhibit enzyme activity or uptake.
Data from the Phase 3 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 hematological 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.
Shire’s VPRIV clinical trial program is the largest and most comprehensive set of Phase 3 trials conducted to date for type 1 Gaucher disease.
Date: November 4, 2010
Source: Shire plc
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