Transition to Zoledronic Acid after Romosozumab Treatment Maintains Bone Mineral Density Gains

Presentation Number: OR08-2
Date of Presentation: April 1st, 2017

M R McClung*1, M A Bolognese2, J P Brown3, J-Y Reginster4, B L Langdahl5, J Maddox6, C Yan7, S Yue6, P D Meisner8 and A Grauer6
1Oregon Osteoporosis Center, Portland, OR, 2Bethesda Health Research Center, Bethesda, MD, 3Laval University and CHU de Québec (CHUL) Research Centre, Québec City, QC, Canada, 4University of Liège, Liège, Belgium, 5Aarhus University Hospital, Aarhus, Denmark, 6Amgen Inc., Thousand Oaks, CA, 7Amgen Ltd, Cambridge, United Kingdom, 8UCB Pharma, Brussels, Belgium

Abstract

Introduction

Romosozumab (Romo) increased bone mineral density (BMD) and bone formation, and decreased bone resorption, resulting in vertebral and clinical fracture risk reduction within 12 months in postmenopausal women with osteoporosis (1). Here we report the efficacy and safety of transitioning to zoledronic acid (Zol) following Romo.

Methods

A phase 2 trial (2) (NCT00896532) enrolled postmenopausal women with a lumbar spine (LS), total hip (TH), or femoral neck (FN) T-score ≤−2.0 and ≥−3.5. In this analysis, women received various Romo doses or placebo (Pbo) from baseline (BL) to month 24, were re-randomized to denosumab (DMAb) or Pbo (month 24‒36), and then all received Romo (210 mg QM) for 12 months (month 36‒48). At month 48, subjects on active treatment (Romo/DMAb/Romo) for 48 months were assigned to no intervention, unless they had a fracture from month 24‒48 or a T-score ≤–2.5 at LS, TH, or FN at month 48 and were subsequently assigned to Zol (5 mg IV). All other subjects received Zol and both groups were followed for 24 months to month 72.

Results

After Romo treatment (month 36‒48), 141 women (90 Zol, 51 no intervention) continued in the study. In the Zol group, LS BMD was maintained through month 48‒72 (percentage change from month 48: ‒0.8%; percentage change from BL at month 72: 12.8%). Similar patterns were observed at the TH (0.1% and 4.2%, respectively) and FN (0.5% and 4.4%, respectively). After no intervention, LS BMD decreased from month 48‒72 (‒10.8%), although remained above BL at month 72 (percentage change from BL at month 72: 4.2%). At the TH and FN, BMD decreased by 6.4% and 5.9% respectively from month 48‒72, reaching values close to BL at month 72. In the Zol group, both median P1NP and CTX levels decreased initially, then moved towards BL by month 72. In the no intervention group, PINP decreased while CTX increased initially and gradually returned towards BL. During month 48‒72, adverse events (AEs) were reported in 83.9% of subjects receiving Zol and 72.5% assigned to no intervention; serious AEs were reported in 13.8% and 15.7% of subjects, respectively. Fragility fractures were reported in 2 Zol (1 radius, 1 rib) and 2 no intervention (1 radius; 1 fibula) subjects, and 1 fatal event occurred in a no intervention subject.

Conclusion

BMD gains at the LS, TH, and FN with prior Romo treatment were generally maintained over 24 months with a single dose of Zol. In women who received no further intervention, BMD decreased, but remained above (LS) or near BL (TH, FN) from month 48‒72.

 

Disclosure: MRM: Consultant, Radius, Consultant, Merck & Co., Speaker Bureau Member, Amgen, Speaker, Amgen, Consultant, Amgen. MAB: Speaker Bureau Member, Amgen, Clinical Researcher, Amgen. JPB: Scientific Board Member, Merck & Co., Speaker Bureau Member, Eli Lilly & Company, Scientific Board Member, Eli Lilly & Company, Principal Investigator, Eli Lilly & Company, Speaker Bureau Member, Amgen, Principal Investigator, Amgen, Scientific Board Member, Amgen. JYR: Consultant, Asahi, Consultant, UCB, Consultant, IBSA-Genevrier, Consultant, Servier, Speaker, Dairy Research Council, Speaker, Pharmevo, Speaker, IBSA-Genevrier, Speaker, Cniel, Speaker, Meda, Speaker, Danone, Speaker, Servier, Speaker, Merck & Co., Investigator, IBSA-Genevrier, Investigator, Cniel, Investigator, Meda, Investigator, Danone, Investigator, Pfizer, Inc., Investigator, Servier, Investigator, Eli Lilly & Company, Investigator, Amgen, Investigator, Merck & Co., Consultant, Radius Health, Consultant, Meda, Consultant, Pierra Fabre. BLL: Advisory Group Member, Amgen, Advisory Group Member, UCB, Speaker, Eli Lilly & Company, Speaker, Merck & Co., Speaker, Amgen, Researcher, Eli Lilly & Company, Researcher, Novo Nordisk, Researcher, Orkla, Advisory Group Member, Eli Lilly & Company, Advisory Group Member, Merck & Co.. JM: Employee, Amgen, Employee, Amgen. CY: Employee, Amgen, Employee, Amgen. SY: Employee, Amgen, Employee, Amgen. PDM: Employee, UCB Pharma, Employee, UCB Pharma. AG: Employee, Amgen, Employee, Amgen.