VPRIV shows some benefits for bone health in Gaucher disease type 1
Study: It may help ease marrow burden, but strength gains appear more modest
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VPRIV (velaglucerase alfa) may help improve bone marrow health in adults with Gaucher disease type 1, but its benefit for bone strength appears to be modest and may vary from patient to patient, a small Phase 4 clinical study found.
The study, “Improvement of Bone Mineral Density in Patients with Type 1 Gaucher Disease Treated with Velaglucerase Alfa: Results from Clinical Studies,” was published in the Journal of Clinical Medicine. Takeda Pharmaceuticals, which markets VPRIV, funded the study.
VPRIV delivers working version of key enzyme
Gaucher disease is caused by mutations in the GBA1 gene, which encodes the enzyme glucocerebrosidase that is needed to break down glucocerebroside, a fatty molecule. When the enzyme is absent or does not work properly, glucocerebroside builds up to toxic levels in certain cells, damaging multiple organs.
VPRIV is an enzyme replacement therapy that delivers a working version of glucocerebrosidase via regular infusions into the bloodstream. By helping break down excess glucocerebroside, VPRIV is expected to ease symptoms of Gaucher disease.
The therapy is approved to treat Gaucher disease type 1, the most common form of Gaucher, whose symptoms commonly include low red blood cells and platelets (needed for blood clotting) and an enlarged spleen and liver. Bone pain, fractures, and other complications can also occur because the affected Gaucher cells can infiltrate the bone marrow, the soft spongy tissue inside bones, and reduce blood supply to the bones.
Small improvement seen in bone density in the lower spine
Reports suggest that VPRIV may increase bone density in patients with brittle bones. To better understand the benefits of VPRIV for bone health in adults with Gaucher disease type 1, the researchers conducted a Phase 4 clinical study (NCT02574286) involving 21 patients. Of these, 16 completed the full two years of the study.
Ten of these patients (62.5%) had osteopenia, a loss of bone density below normal reference values. The other six (37.%) had osteoporosis, an advanced state of osteopenia where bones become damaged to a point where they can break easily. On average, patients received about 42 infusions of VPRIV, which are normally given every two weeks. Fifteen patients also received vitamin D supplementation, which helps bones absorb calcium.
Over 2 years, there was a small improvement in bone density in the lower spine, as measured by dual-energy X-ray absorptiometry, but this change was not statistically significant. However, when the researchers combined data from 40 patients treated with VPRIV in three previous clinical trials, there was a significant improvement in bone density.
Findings from this study and from a pooled analysis of previously collected clinical data confirm that [VPRIV] continues to demonstrate efficacy in clinical outcomes with a consistent safety profile and has beneficial effects on bone disease.
The researchers also looked at bone marrow burden, which measures the extent of Gaucher cells in the bone marrow. In this measure, a lower score means less disease activity. Over two years, there was a significant reduction in bone marrow burden, suggesting that VPRIV helped reduce the toxic buildup of Gaucher cells in the bone marrow.
As in previous studies, treatment with VPRIV also resulted in significant increases in hemoglobin, the protein that carries oxygen in red blood cells, and platelets. The size of the liver and spleen also decreased significantly, as did lyso-Gb1 levels, a biomarker of Gaucher disease severity.
All patients had at least one side effect, but most were mild or moderate. About half of the participants had treatment-emergent side effects — mostly back pain, headache, and arm or leg pain — that occurred during or shortly after an infusion. Three patients stopped treatment because of serious side effects.
“Findings from this study and from a pooled analysis of previously collected clinical data confirm that [VPRIV] continues to demonstrate efficacy in clinical outcomes with a consistent safety profile and has beneficial effects on bone disease,” the researchers concluded.
