SUN-757 Sustained Improvements in Patient-Reported Outcomes Across Age Groups in Burosumab-Treated X-linked Hypophosphatemia (XLH): Results From the XLH Disease Monitoring Program

Abstract Disclosure: A.A. Khan: Ascendis, Alexion Pharmaceuticals, Inc., Amolyt, Bridge Bio, Takeda. T.O. Carpenter: Kyowa Kirin, Ultragenyx. J. Simmons: Kyowa Kirin, Ultragenyx. H. Cassinelli: None. E.A. Imel: Kyowa Kirin, Ultragenyx. P.F. Florenzano: Kyowa Kirin, Ultragenyx. B. Johnson: Kyowa Kirin, Kyowa Kirin. E. Yang: Ultragenyx. H.M. Heerssen: Kyowa Kirin. J. Li: Kyowa Kirin. L.M. Ward: Kyowa Kirin, Ultragenyx. Introduction: Burosumab, a fully human FGF23-neutralizing antibody, improved outcomes in adults and children with X-linked hypophosphatemia (XLH) in 24- and 64-week randomized controlled trials, respectively. This analysis describes real-world changes in patient-reported outcomes (PROs) over ≤3 years (y) in burosumab-treated individuals with XLH, including age groups with previously limited data (13-17 and >65y). Methods: Participants (pts) initiating burosumab after enrollment and before the Year (Y) 1 visit in the XLH Disease Monitoring Program (DMP); NCT03651505, a multi-country observational study) were evaluated. In children, change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) T-scores at Y1 and 3 were evaluated to assess fatigue, pain interference, and physical function (PF) mobility. In adults, change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and PROMIS PF T-scores at Y1 and 3 visits were evaluated to assess pain severity, joint stiffness, and PF. Results: At baseline (N=116) and Y1 (n=108), most groups included >10 pts, but the >65y group included 3. Y3 (n=76) group sample size range was 3-22. In children (n=83), mean ± standard deviation (SD) PROMIS pain interference improved significantly at Y1 (n=36: −3.6 ± 8.5, P=0.016) and Y3 (n=29: −4.8 ± 10.1, P=0.017). Mean PROMIS fatigue and PF mobility improved descriptively at Y1 and 3. The 5-12y group showed descriptive improvements in all PROMIS domains at Y1 and 3, with a significant change for pain at Y1 (n=25: −4.2 ± 7.3, P=0.008). The 13-17y group showed descriptive improvements in fatigue and pain interference at Y1 and 3. In adults (n=72), mean ± SD WOMAC scores improved significantly at Y1 (pain: −7.5 ± 18.8, P=0.001; stiffness: −12.2 ± 23.6, P<0.0001; PF: −6.3 ± 15.5, P=0.001), and Y3 (n=47) (pain: −11.3 ± 16.9, P<0.0001; stiffness: −16.8 ± 21.7, P<0.0001; PF: −10.8 ± 16.6; P<0.0001). Mean ± SD PROMIS PF score improved significantly at Y1 (1.5 ± 5.6, P=0.025) and remained stable at Y3 (1.6 ± 5.8). All adult groups had descriptive reductions from baseline in all WOMAC domains at Y1 and 3. Significant improvements in mean ± SD scores were seen at Y1 and 3 for pain in the 30-39y (Y1: −7.5 ± 11.3, P=0.0036; Y3: −10.3 ± 12.2, P=0.0054) and 50-64y (Y1: −13.3 ± 18.9, P=0.0333; Y3: −21.9 ± 13.1, P=0.0021) groups, stiffness in the 18-29y (Y1: −22.1 ± 28.5, P=0.057; Y3: −25.0 ± 23.2, P=0.0185) and 30-39y (Y1: −10.4 ± 17.9, P=0.0092; Y3: −13.3 ± 19.2, P=0.175) groups, and PF in the 50-64y (Y1: −8.7 ± 13.5, P=0.0467; Y3: −14.9 ± 9.1, P=0.0023) group. Conclusion: Children with XLH showed early and sustained improvement in pain interference. Adults with XLH also showed significant improvements at DMP Y1 and 3 in all WOMAC domains. Despite small sample sizes, this analysis provides real-world data on the positive impact of burosumab treatment on PROs. Presentation: Sunday, July 13, 2025