OR13-2 Characterizing the Impact of Burosumab on Bone Health in Children with X-Linked Hypophosphatemia: Results from Year 1 of the Disease Monitoring Program

Abstract

Abstract X-linked hypophosphatemia (XLH) is a rare, heritable disorder wherein excess FGF23 leads to renal phosphate wasting and impaired activation of vitamin D. XLH is characterized by rickets and osteomalacia leading to bone pain, skeletal deformities, and short stature. The XLH Disease Monitoring Program (DMP; NCT03651505) is a prospective, multinational outcomes study of the longitudinal progression of clinical, radiographic, and biochemical features of XLH in children and adults. We assessed the impact of the recombinant human IgG1 monoclonal antibody to FGF23, burosumab, on measures of bone health in children with XLH at Year 1 of the DMP. As of March 2021, 287 children (<18 years) had completed the Year 1 visit. Participants were grouped by when they first received burosumab: Group 1, prior to DMP enrollment (N=68; mean (SD) age 9.5 (3.6) years); Group 2, during the DMP (N=150; 8.7 (5.0) years); Group 3, never, but receiving conventional therapy (N=69; 8.8 (5.3) years). Before receiving burosumab, serum phosphorus levels were below normal; after burosumab initiation, serum phosphorus in Groups 1 and 2 rapidly normalized, with sustained improvements up to 3 years of treatment. Serum phosphorus remained low in Group 3. Before burosumab, serum alkaline phosphatase levels were above normal; with continued burosumab therapy, mean levels gradually declined towards normal and were maintained for up to 4 years. The Radiographic Global Impression of Change (RGI-C) assessed rickets and lower limb deformity from DMP baseline to Year 1, with positive values denoting improvement. Mean (SD) RGI-C rickets global scores were +1.0 (0.9) for Group 1 (n=44), +1.5 (0.7) for Group 2 (n=39), and +0.3 (1.2) for Group 3 (n=3). Lower limb deformity RGI-C scores were +0.3 (0.6) for Group 1 (n=42), +0.4 (0.8) for Group 2 (n=39), and +0.8 (1.1) for Group 3 (n=3). Height Z-score change from DMP baseline at Year 1 was 0.1 (0.3) for Group 1 (n=58), 0.1 (0.4) for Group 2 (n=90), and -0.8 (3.1) for Group 3 (n=18). There were no new safety concerns or reports of hyperphosphatemia. These real-world data affirm that normalization of serum phosphorus is rapid and sustained following burosumab initiation, resulting in improved serum alkaline phosphatase levels which positively impact bone mineralization. Improvements in rickets, growth, and lower limb deformity occur in the first year of burosumab treatment and continue in those who started burosumab prior to entering the DMP. The absence of new safety concerns or reports of hyperphosphatemia up to 4 years after burosumab initiation is also notable. The 10-year DMP study design will provide understanding of long-term effects in these patients with continued burosumab therapy. Presentation: Sunday, June 12, 2022 11:15 a.m. - 11:30 a.m.