Burosumab for the treatment of tumor-induced osteomalacia (UX023T-CL201)
In 14 adults whose bones had softened because a hidden tumour was making them lose phosphate, blocking the hormone responsible brought blood phosphate back to normal for nearly three years and let a third of their fractures heal fully.
Overview
Report of UX023T-CL201 (NCT02304367), an open-label phase 2 study of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with tumour-induced osteomalacia or cutaneous skeletal hypophosphataemia syndrome. The analysis covers 14 patients with tumour-induced osteomalacia after excluding two found to have X-linked hypophosphataemia after enrolment and one with cutaneous skeletal hypophosphataemia syndrome. Key endpoints were changes in serum phosphorus and osteomalacia assessed on transiliac bone biopsies at week 48.
Serum phosphorus increased from a baseline of 0.52 mmol/L and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p less than 0.0001). Most measures of osteomalacia improved at week 48: osteoid volume per bone volume, osteoid thickness and mineralisation lag time decreased, while osteoid surface per bone surface did not change. Of 249 fractures or pseudofractures detected at baseline across the 14 patients, 33 percent were fully healed and 13 percent partially healed at week 144. Patients reported less pain and fatigue and better physical health. Two patients discontinued; 16 serious adverse events occurred in seven patients and there was one death, all considered unrelated to treatment; nine patients had 16 treatment-related adverse events, all mild to moderate.
- Serum phosphorus rose from 0.52 mmol/L at baseline to 0.91 mmol/L at week 22 and 0.82 mmol/L at week 144 (p<0.0001).
- Of 249 baseline fractures or pseudofractures, 33 percent were fully healed and 13 percent partially healed at week 144.
- All 16 serious adverse events and the one death were judged unrelated to burosumab; treatment-related events were mild to moderate.
This is the main evidence behind the tumour-induced osteomalacia indication for burosumab in the EU and the US. For the rare patient whose phosphate-wasting tumour cannot be found or resected, it offers a way to treat the metabolic disease directly instead of relying on oral phosphate and active vitamin D.
- Single-arm open-label study of 14 analysed patients; no control group.
- Three enrolled patients were excluded from the analysis after enrolment, so the registry's 17 differs from the 14 reported.
- Sponsor-run study with sponsor employees among the authors.