ECEESPE2025 Poster Presentations Bone and Mineral Metabolism (112 abstracts)
Consistent reduction in rate of fracture with setrusumab therapy in patients with osteogenesis imperfecta: month 14 data from phase 2 of the orbit study
Luigi Picaro 1 , Gary Gottesman 2 , Thomas Carpenter 3 , Danita Velasco 4 , Maegen Wallace 5 , Peter Smith 6 , Erik Imel 7 , Diana Luca 8 , Heather Byers 8 , Stanley Krolczyk 8 & E Michael Lewiecki 9
1Mereo BioPharma, London, UK; 2Washington University School of Medicine, St. Louis, Missouri, USA; 3Yale University School of Medicine, New Haven, CT, USA; 4Children’s Nebraska, Omaha, NE, USA; 5Phoenix Children’s Hospital, Phoenix, AZ, USA; 6Shriner’s Hospitals for Children, Chicago, IL, USA; 7Indiana University School of Medicine, Indianapolis, Indiana, USA; 8Ultragenyx Pharmaceuticals Inc., Novato, CA, USA; 9University of New Mexico Heath Sciences Center, Albuquerque, NM, USA
JOINT1843
Osteogenesis imperfecta (OI) is a rare bone disorder characterize by increased fragility and low bone mass. Setrusumab is a fully human anti-sclerostin monoclonal antibody that has demonstrated improved bone mineral density (BMD), strength, and remodeling in adult patients with OI. Here, we assess the efficacy and safety of setrusumab in children and young adults with OI through Month 14 of Phase 2 of the Phase 2/3 Orbit study (NCT05125809). Participants with OI Types I, III, or IV aged 5 to <26 years randomized 1:1 received setrusumab at 20 or 40 mg/kg monthly doses intravenously. After all participants had received setrusumab for 6 months, the 20 mg/kg dose was selected and all participants switched to this dose through the end of the study. 24 participants were assessed: 12/24 (50%) are female, 18/24 (75%) are <18 years of age, and 17/24 (71%) and 7/24 (29%) have OI Types I and III/IV, respectively. Participants received setrusumab for a mean 16 months at the time of analysis, and most (18/24, 75%) received bisphosphonates prior to enrollment. Baseline assessments of BMD showed continued improvements through Months 6 and 12. A mean (S.E.) change from baseline in lumbar spine BMD of 14% (±2%) was observed at Month 6 and continued to 22% (±3%) at Month 12 (P<0.0001). This equated to an improvement from baseline in BMD Z-score of 0.9 (±0.1) at Month 6 and 1.2 (±0.2) at Month 12 (P<0.0001). The baseline median annualized rate of skeletal fracture (excluding fingers, toes, face, skull, and morphometric vertebral fractures) prior to treatment of 0.72 decreased to 0 (P=0.0014). A reduction in fracture rate of 67% was calculated. No safety concerns were identified at Month 14. Treatment-emergent adverse events (TEAE) were consistent with the anticipated safety profile of setrusumab. Most reported related TEAEs (11/12, 92%) were mild (Grade 1), with no related serious TEAEs. Importantly, no cardiovascular TEAEs were reported through Month 14, and none of the reported TEAEs led to discontinuation of the study by any participant, or disruption in setrusumab treatment. Data from Month 14 of Phase 2 of the Orbit study indicated notable improvements in BMD with setrusumab therapy in participants with OI. We report a meaningful reduction in the annualized rate of skeletal fractures (67%) with setrusumab therapy. Overall, the findings herein support those data reported after 6 months of setrusumab therapy, confirming the robust and durable response in participants with OI.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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