OR13-1 Long-Term Burosumab Therapy Provides Sustained Benefit in Patients with Tumor-Induced Osteomalacia: End of Study Findings From the Pivotal Phase 2 Study

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome wherein small tumors secrete excess fibroblast growth factor 23 (FGF23) leading to hypophosphatemia, osteomalacia, bone pain, fractures, and muscle weakness. Burosumab is an anti-FGF23 monoclonal antibody approved for treatment of TIO. We report end of study (EOS) data from the open-label phase 2 UX023T-CL201 trial (NCT02304367) of burosumab in adults with TIO. In UX023T-CL201, participants received burosumab (0.3–2.0 mg/kg) by subcutaneous injection every 4 weeks for 48 weeks with an extension up to 300 weeks (∼6 years). Co-primary endpoints were change in serum phosphorus at Week 24 and change in excess osteoid by trans-iliac crest bone biopsy at Week 48. Additional endpoints included changes in bone biomarkers, activity on radionucleotide bone scan representing fractures/pseudofractures, patient-reported outcomes, and safety measures. This analysis included 14/17 UX023T-CL201 participants; excluding those with other diagnoses (n=3). Mean (SD) serum phosphorus improved from 1.6 (0.5) mg/dL at baseline to 2.3 (0.5) mg/dL when averaged across the mid-point of the dose interval through Week 24 (co-primary endpoint). Levels further improved (2.6 [0.4] mg/dL; n=7) to within the normal range (2.5–3.6 mg/dL) at Week 240. Most measures of osteomalacia improved at Week 48 (co-primary endpoint), including osteoid/bone volume, osteoid thickness, and mineralization lag time. However, osteoid surface/bone surface showed no change. Bone biomarkers (P1NP, CTx, BALP) followed similar trends. Upon initiation of burosumab, markers briefly increased by Week 24 as bone healing began, then gradually decreased with further treatment, reaching normal (P1NP, CTx) or near-normal (BALP) ranges by Week 240. At baseline, 249 areas of increased radionucleotide uptake indicating fracture activity were detected across 14 participants. By Week 144, 36% (72/201) and 13% (26/201) regions of abnormal uptake were fully or partially restored, respectively. By EOS, further reduction of active fractures and fewer new areas of uptake were observed. New fractures at Week 144 were observed in a single participant (considered a burosumab partial responder) and between Week 144 and EOS in another participant unrelated to burosumab (car accident). Participants reported sustained mean reduction from baseline pain at Week 240 per Brief Pain Inventory and significantly per SF-36 Bodily Pain score. Significant reductions in baseline fatigue at Week 240 were reported per Brief Fatigue Inventory and SF-36 Vitality scores. SF-36 physical health (Role Physical, Bodily Pain, Component Score) and mental health (Social Function, Vitality) significantly improved from baseline at Week 240. The observed safety profile of long-term burosumab in participants with TIO was consistent with the known safety profile of burosumab and similar to patients with XLH. Long-term burosumab therapy was associated with improved serum phosphorus, osteomalacia, bone turnover, fracture incidence and healing, health-related quality of life, and reductions in pain and fatigue in adults with TIO. Presentation: Sunday, June 12, 2022 11:00 a.m. - 11:15 a.m.