SUN-718 Results From A Phase 1, Open-label, Ascending Multiple-dose Study To Evaluate Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Romosozumab In Children And Adolescents With Osteogenesis Imperfecta And Phase 3 Study Rationale

Abstract Disclosure: D. El-Maouche: Amgen Inc, Employee and stock holder. R. Jeswani: Amgen Inc, Employee and stock holder. W. Sohn: Amgen Inc, Employee and stock holder. L. Zhou: Amgen Inc, Employee and stock holder. O. Semler: Amgen Inc, Honoraria for consultancy. There are no osteogenesis imperfecta (OI) treatments approved for pediatric patients in the US. Romosozumab (Romo) is a monoclonal antibody, sclerostin inhibitor that increases bone formation and decreases bone resorption. This phase 1 study (NCT04545554) evaluated the pharmacokinetics (PK), safety, and tolerability of Romo in pediatric patients with OI. Ambulatory adolescents (12-<18 years of age) or children (5-<12 years of age) diagnosed with OI were enrolled and each age group received three monthly subcutaneous doses of Romo at one of three dose levels (1 mg/kg, 3 mg/kg, and 5 mg/kg) in both age groups; four patients per cohort). The primary endpoints evaluated PK parameters. Secondary endpoints included bone turnover markers, lumbar spine areal bone mineral density (aBMD), treatment-emergent adverse events (TEAEs), and incidence of antiromosozumab antibodies. Overall, 25 participants were enrolled (mean age, 10.5 years; 64% male; 88% White). Systemic Romo exposure after the first and third dose administration increased with increasing dose levels in both age groups, with higher exposures in adolescents than children. There was no clear dose response in serum type 1 collagen C-telopeptide levels. There appeared to be a dose response in procollagen type 1 N-terminal propeptide (P1NP) levels. P1NP levels increased by up to 58.6% in adolescents and 28.4% in children at day 15 after dosing before returning towards baseline levels prior to the next dose. The lumbar spine aBMD mean percentage increase from baseline to day 169 after 3 months of treatment ranged from 7.1% to 15.0% in adolescents and 7.1% to 12.7% in children. Overall, 12/25 (48%) participants experienced TEAEs during the study or follow-up period. TEAEs were generally mild or moderate; two participants had serious TEAEs of femur fracture and lower-limb fracture (both unrelated to Romo). No specific pattern of any reported TEAEs was identified. Out of 25 participants, 5 (20%) developed antiromosozumab antibodies with 3 of the 5 patients developing neutralizing antibodies. No adverse events related to lack of efficacy, changes in PK, or hypersensitivity were reported or observed in participants with antiromosozumab antibodies. These preliminary results show that Romo is well tolerated in a pediatric population with OI and may have positive effects on P1NP response and increase aBMD after 3 months. Based on these findings, Romo will be used in an open-label phase 3 study aiming to enroll 106 pediatric patients. The efficacy of 12-month Romo treatment in OI will be measured by change in lumbar spine BMD Z-score and number of fractures. Presentation: Sunday, July 13, 2025