Post hoc Clinical Parameters
Patients meeting pre-defined clinical parameters at 4 years2
STUDY DESIGN
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A post hoc analysis was conducted on 39 treatment-naïve patients, aged 6–62 years, from the Study 032 and 039 populations who enrolled in the 044 extension trial. This analysis assessed achievement of published pre-defined clinical parameters at baseline and yearly intervals after initiation of VPRIV for up to 4 years.2
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PRIMARY ENDPOINT: to measure the number of patients who met these pre-defined clinical parameter expectations in hemoglobin and platelet concentration, and spleen and liver volumes.2
Study Limitations:
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Benefits of achieving clinical parameters for a patient’s long-term clinical outcomes have not been demonstrated, and composite analyses may be required to assess the effect of ERT on Gaucher disease, instead of individual assessments.2 This analysis does not cover the primary or secondary endpoints of the 044 extension trial (Hughes et al. publication). This was a post hoc analysis.
Hemoglobin concentration2
PLATELET COUNT2
SPLEEN VOLUME2
LIVER Volume2
Pre-defined
clinical
parameters:
>11 g/L for females or patients 12 years and younger
>12 g/dL for males or patients older than 12 years
≥100% increase if baseline is <60 × 109/L
≥100 × 109/L if baseline is ≥60 and <120 × 109/L
≥120 × 109/L if baseline is ≥120 × 109/L
≥50% decrease
compared with
baseline (or ≤8.0 MN)
≥30% decrease
compared with
baseline (or ≤1.5 MN)
Parameter
met by:
19/20 patients (95%)
20/20 patients (100%)
16/16 patients (100%)
15/16 patients (94%)
Pre-defined clinical parameters:
Hemoglobin concentration2
>11 g/L for females or patients 12 years and younger
>12 g/dL for males or patients older than 12 years
PLATELET COUNT2
≥100% increase if baseline is <60 × 109/L
≥100 × 109/L if baseline is ≥60 and <120 × 109/L
≥120 × 109/L if baseline is ≥120 × 109/L
SPLEEN VOLUME2
≥50% decrease
compared with
baseline (or ≤8.0 MN)
LIVER Volume2
≥30% decrease
compared with
baseline (or ≤1.5 MN)
Parameter met by:
19/20 patients (95%)
20/20 patients (100%)
16/16 patients (100%)
15/16 patients (94%)
Over the 4 years, pre-defined clinical parameters were also maintained by 100% of patients who had already met these at baseline.2
These are observational data, therefore cautious interpretation is advised. The clinical significance of these data is unknown. There are no official treatment guidelines for type 1 Gaucher disease, therefore clinical parameters were pre-defined by Pastores et al., based on medical literature data and the clinical experience of an international panel of physicians.2
MN, multiples of normal.
Exploratory Efficacy Objective — Bone Mineral Density (BMD) Z-Score
Efficacy of VPRIV in improving BMD Z-score was assessed as an exploratory efficacy objective
in treatment-naïve patients.2*
STUDY DESIGN
In the 044 analysis of the Study 032 and 039 populations, efficacy of VPRIV in improving bone mineral density (BMD) Z-score was assessed as an exploratory efficacy objective.2*
Study Limitations:
-
These data were from an exploratory objective from an open-label extension study and had less evidentiary value than the primary and secondary objectives. Further confirmatory studies are required to draw any conclusions from these data.2
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BMD was assessed using dual-energy X-ray absorptiometry (DXA) of the lumbar spine in patients ≥18 years of age.2
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Drifts in calibration can occur in individual scanners over time, as can breakpoints. Longitudinal quality assurance (QA) data were collected from scanners and corrective calculations were made, if needed. A post hoc cross-calibration of DXA scanners was necessary to pool study data collected from multiple centers, and this increased the likelihood of detecting a possible treatment effect. Where sites were missing QA data, an assumption of no drift was made, which may have affected the accuracy of the DXA results.2
Of the 31 patients in this analysis, four patients used bisphosphonates during the initial trial, the extension study, or both. Bisphosphonates affect bone turnover and BMD.2
Mean change in femoral neck BMD Z-score was not statistically significant.2
*Data shown exclude patients previously treated with imiglucerase from Study 039
MEAN CHANGE OVER TIME IN LUMBAR SPINE BMD FROM BASELINE2†
Error bars show 95% CI. Clinical significance of these data is unknown.
Mean change, Z-scoreAt 24 months in Study 044:2
+0.62 SD
mean increase in BMD Z-score
in the lumbar spine (n=31)
Median BMD Z-score at baseline:† -1.73 SD (-4.20, 0.78)2
Overall velaglucerase alfa
Overall velaglucerase alfa, no bisphosphonates
Imiglucerase-velaglucerase alfa
Imiglucerase-velaglucerase alfa, no bisphosphonates
†Baseline was before the first dose in the initial trials
CI, confidence interval; SD, standard deviation.
