Chung Yoon-Sok, Langdahl Bente, Plebanski Rafal, Czerwinski Edward, Dokoupilova Eva, Supronik Jerzy, Rosa Jan, Mydlak Andrzej, Sapula Rafal, Rowińska-Osuch Anna, Baek Ki-Hyun, Urboniene Audrone, Mordaka Robert, Ahn Sohui, Rho Young Hee, Ban Jisuk, Eastell Richard
Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea; Institute on Aging, Ajou University Medical Center, Suwon, Republic of Korea.
Department of Endocrinology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Bone. 2025 Mar;192:117371. doi: 10.1016/j.bone.2024.117371. Epub 2024 Dec 12.
This study evaluated the efficacy, safety, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of SB16 versus reference denosumab (DEN) up to 18 months in postmenopausal osteoporosis (PMO) patients, and assessed outcomes after switching from DEN to SB16 compared to those who continued with DEN or SB16.
457 PMO patients were initially randomized, with 407 re-randomized at Month 12 to either continue DEN (DEN+DEN), switch to SB16 (DEN+SB16), or continue SB16 (SB16 + SB16) through Month 18. Efficacy was assessed by the percent change from baseline in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck. Safety, PD, PK, and immunogenicity were evaluated throughout the study period.
Mean percent changes from baseline in lumbar spine, total hip, and femoral neck BMD at Month 18 were comparable across treatment groups, indicating comparable efficacy between SB16 and DEN. The mean percent change in lumbar spine BMD was 6.8 % (SB16 + SB16), 6.2 % (DEN+SB16), and 6.8 % (DEN+DEN). Total hip BMD increased by 4.4 %, 3.5 %, and 4.0 %, and femoral neck BMD by 3.4 %, 3.1 %, and 2.7 % for SB16 + SB16, DEN+SB16, and DEN+DEN, respectively. Safety profiles were similar among groups, with no new safety concerns identified after switching. Only one patient in the DEN+SB16 group developed non-neutralizing anti-drug antibodies by Month 18, indicating a low immunogenicity risk for SB16.
Switching from DEN to SB16 demonstrated comparable efficacy, safety, PD, PK, and immunogenicity in PMO patients relative to those who continued DEN. SB16 was well tolerated over 18 months, demonstrating comparable outcomes to DEN.
本研究评估了SB16对比参比药物地诺单抗（DEN）在绝经后骨质疏松症（PMO）患者中长达18个月的疗效、安全性、药效学（PD）、药代动力学（PK）及免疫原性，并比较了从DEN转换为SB16的患者与继续使用DEN或SB16的患者的结局。
457例PMO患者最初被随机分组，其中407例在第12个月重新随机分组，分别继续使用DEN（DEN+DEN）、转换为SB16（DEN+SB16）或继续使用SB16（SB16+SB16）至第18个月。通过腰椎、全髋和股骨颈骨密度（BMD）相对于基线的变化百分比评估疗效。在整个研究期间评估安全性、PD、PK及免疫原性。
在第18个月时，各治疗组腰椎、全髋和股骨颈BMD相对于基线的平均变化百分比相当，表明SB16和DEN疗效相当。腰椎BMD的平均变化百分比在SB16+SB16组为6.8%，DEN+SB16组为6.2%，DEN+DEN组为6.8%。SB16+SB16组、DEN+SB16组和DEN+DEN组的全髋BMD分别增加了4.4%、3.5%和4.0%，股骨颈BMD分别增加了3.4%、3.1%和2.7%。各组的安全性概况相似，转换后未发现新的安全问题。DEN+SB16组仅1例患者在第18个月时产生了非中和性抗药物抗体，表明SB16的免疫原性风险较低。
相对于继续使用DEN的患者，从DEN转换为SB16的PMO患者在疗效、安全性、PD、PK及免疫原性方面相当。SB16在18个月内耐受性良好，与DEN的结局相当。
