Improvement of bone mineral density in patients with type 1 Gaucher disease treated with velaglucerase alfa: results from clinical studies

Background: Despite the availability of effective therapies for Gaucher disease (GD), management of skeletal disease manifestations remains challenging. Methods: This phase 4 SHP-GCB-402 study evaluated the effect of velaglucerase alfa on lumbar spine (LS) bone outcomes in patients with type 1 GD. Results: Twenty-one patients with documented bone pathology received ≥1 dose of velaglucerase alfa 60 U/kg; 16 completed this study. The primary endpoint—change from baseline to 24 months in an LS bone mineral density (BMD) Z-score measured by dual-energy X-ray absorptiometry—showed a numerical improvement from baseline (mean [SD] −1.93 [0.88]) to 24 months (−1.76 [1.00]), although statistical significance was not reached (p = 0.1077). These changes are not consistent with previous velaglucerase alfa studies. To contextualize these findings, a pooled analysis of 24-month data from previous velaglucerase alfa trials was conducted. In this cohort (n = 40), a statistically significant mean (SD) increase in the LS BMD Z-score of 0.55 (0.58; p < 0.0001) was observed, supporting the therapeutic potential of velaglucerase alfa in improving skeletal outcomes. Additionally, SHP-GCB-402 demonstrated a significant reduction in the bone marrow burden (BMB) score (mean change from baseline: −3.0 [2.27]; p = 0.0005), indicating a positive effect on bone marrow infiltration. All patients experienced ≥1 treatment-emergent adverse event, mostly of mild/moderate severity. Conclusions: The observed numerical improvements in BMD and significant improvements in BMB in SHP-GCB-402 along with pooled BMD data suggest that velaglucerase alfa may confer skeletal benefits while maintaining a consistent safety profile.