ICCBH2017 Poster Presentations (1) (209 abstracts)
Effects of KRN23, a fully human anti-FGF23 monoclonal antibody, on functional outcomes in children with X-linked hypophosphatemia (XLH): results from a randomized, open-label Phase 2 study
Erik Imel 1 , Thomas Carpenter 2 , Agnès Linglart 3 , Annemieke Boot 4 , Wolfgang Högler 5 , Raja Padidela 6 , William van’t Hoff 7 , Anthony Portale 8 , Meng Mao 9 , Alison Skrinar 9 , Javier San Martin 9 & Michael P Whyte 10
1Indiana University School of Medicine, Indianapolis, IN, USA; 2Yale University School of Medicine, New Haven, CT, USA; 3Hôpital Bicêtre, Le Kremlin-Bicêtre, France; 4University of Groningen, Groningen, The Netherlands; 5Birmingham Children’s Hospital, Birmingham, UK; 6Royal Manchester Children’s Hospital, Manchester, UK; 7Great Ormond Street Hospital, London, UK; 8University of California, San Francisco, San Francisco, CA, USA; 9Ultragenyx Pharmaceutical Inc., Novato, CA, USA; 10Shriners Hospital for Children, St Louis, MO, USA.
Objectives: In XLH, musculoskeletal outcomes of current treatment with oral phosphate (Pi)/active vitamin D are suboptimal for many patients. In a Phase 2, open-label study, we tested the hypothesis that KRN23 improves rickets and functional outcomes in XLH children.
Methods: Fifty-two children with XLH (ages 5–12 years at baseline) received KRN23 subcutaneously biweekly (Q2W) or monthly (Q4W). At study entry, most participants had received oral Pi/active vitamin D for a mean duration of ~7 years. Rickets severity score, walking ability (six-minute walk test [6MWT]), and patient-reported pain and functional disability (Pediatric Outcomes Data Collection Instrument [PODCI]) were assessed at baseline and at Week 40 (Wk40).
Results: Serum Pi was increased significantly through 40 weeks. Mean Thacher Rickets Severity Score improved from baseline by 61% for Q2W, 37% for Q4W, and 50% overall (each P<0.001). Walking ability also improved from mean distance by +23 m at Baseline to Wk40 by (P=0.0037). At Baseline, 24/52 (46%) children had walking impairment defined as 6MWT distance <80% predicted for age. Among those with impaired walking, 6MWT distance increased from 70% of that predicted to 80% (Q2W dosing, n=14) and from 66% to 71% (Q4W dosing, n=10). KRN23 treatment was also associated with significantly improved pain and functional ability. Overall at Wk40, the Sport/Physical Function domain improved by +9.5, Pain/Comfort by +7.5, and Global Functioning by +8.6 (each P<0.0001). Substantial functional impairment at baseline (PODCI Global Functioning score <40) was present in 28/52 (54%) children (mean score of 25.2; >2 SD below the normal mean of 50, 1 SD=10). The domains of Sports/Physical Function and Pain/Comfort were particularly affected (Baseline means of 22.0 and 23.9 respectively). At 40 weeks of KRN23 treatment, the Global Functioning, Sports/Physical Function, and Pain/Comfort domain scores increased by +17.0,+16.7, and +17.4, respectively (each P<0.0001), bringing values into or near the normal range.
Conclusion: In children with XLH, impairments in walking ability, physical function, and pain persist despite standard of care treatment. Our data suggest that KRN23 substantially improves these key functional outcome measures.
Disclosure: Hogler: travel, consulting fees from Ultragenyx; Portale: travel fees, advisory panel from Ultragenyx; Carpenter: grant support, travel fees from Ultragenyx; Imel, Boot, Linglart, van’t Hoff: travel, consulting fees from Ultragenyx; Padidela: consulting f.
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