Retreatment with Romosozumab after 12 Months of Placebo Demonstrates Similar BMD Efficacy Compared with Initial Romosozumab Treatment

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

D L Kendler*1, H G Bone2, F Massari3, E Gielen4, S Palacios5, J Maddox6, C Yan7, C Libanati8, S Yue6 and A Grauer6
1University of British Columbia, Vancouver, BC, Canada, 2Michigan Bone and Mineral Clinic, Detroit, MI, 3Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina, 4UZ Leuven, Leuven, Belgium, 5Instituto Palacios, Madrid, Spain, 6Amgen Inc., Thousand Oaks, CA, 7Amgen Ltd, Cambridge, United Kingdom, 8UCB Pharma, Brussels, Belgium

Abstract

Introduction

Romosozumab (Romo) has a dual effect of increasing bone formation and decreasing bone resorption and is associated with vertebral and clinical fracture risk reduction within 12 months (1). We present the results of 12-months Romo retreatment in subjects initially treated with Romo followed by placebo (Pbo) or denosumab (DMAb).

Methods

Postmenopausal women with a lumbar spine (LS), total hip (TH), or femoral neck (FN) T score ≤−2.0 and ≥−3.5 were enrolled in a phase 2 study (2) (NCT00896532). A total of 139 subjects entered the 12-month Romo 210 mg QM retreatment phase at month 36 after being randomized to various Romo doses from baseline (BL) to month 24, followed by Pbo or DMAb (month 24‒36). Here we report the results of retreatment for the group that was initially randomized to Romo 210 mg QM (n=35).

 

Results

Romo retreatment after Pbo resulted in bone mineral density (BMD) increases at the LS, TH, and FN comparable to the initial Romo treatment. BMD increased by 12.7% from month 36‒48 (12.0% BL‒month 12; 17.6% BL‒month 48) at the LS, 5.8 % (5.5% BL‒month 12; 7.1% BL‒ month 48) at the TH, and 6.3% (5.4% BL‒month 12; 8.6% BL‒month 48) at the FN. In subjects initially treated with Romo followed by DMAb for 12 month, then retreated with Romo, BMD increased by 2.8% from month 36‒48 (12.6% BL‒month 12; 22.1% BL‒month 48) at the LS, while no further BMD increase was noted at TH (7.3% BL‒month 36 and BL‒month 48) or FN (6.3% BL‒month 36; 6.7% BL‒month 48) in the retreatment phase. Bone formation (P1NP) and bone resorption (CTX) patterns were similar in Romo retreatment subjects after Pbo to subjects who received Romo in the first 12 months. In subjects who had received DMAb, reduced levels of both P1NP and CTX increased gradually after Romo retreatment to 52.1% and 16.5%, respectively, at month 48 from BL. The safety profile of Romo retreatment was generally consistent with Romo treatment from BL‒month 24. Of the 140 subjects initially exposed to Romo, 2 subjects previously antibody negative developed binding antibodies during retreatment, none had neutralizing activity; 6 subjects had neutralizing antibodies at the start of retreatment, 1 subject remained positive at the end of retreatment.

Conclusion

After a 12-month treatment-free period, Romo retreatment increased BMD at the spine and hip to an extent similar to initial Romo treatment. Romo retreatment after DMAb resulted in further increases in BMD at the spine and maintenance of BMD at the hip. Safety findings were similar to the initial Romo treatment.

 

Disclosure: DLK: Data Safety Advisory Board, Merck & Co., Principal Investigator, Astra Zeneca, Principal Investigator, Astellas, Speaker, Eli Lilly & Company, Principal Investigator, Eli Lilly & Company, Consultant, Eli Lilly & Company, Speaker, Amgen, Principal Investigator, Amgen, Consultant, Amgen. HGB: Consultant, Amgen, Speaker, Amgen, Investigator, Amgen, Data and Safety Monitoring Board Member, Grunenthal, Consultant, Merck & Co., Investigator, Merck & Co., Consultant, Radius, Consultant, Shire, Speaker, Shire, Consultant, Sucampo. SP: Advisory Group Member, Novo Nordisk, Speaker, Servier, Speaker, Daiichi Sankyo, Speaker, MSD, Advisory Group Member, Gedeon Richter, Speaker, Gedeon Richter, Advisory Group Member, Procare Health, Speaker, Procare Health, Advisory Group Member, Shionogi, Speaker, Shionogi, Speaker, Teva, Principal Investigator, Pfizer, Inc., Principal Investigator, Amgen, Principal Investigator, Gedeon Richter, Principal Investigator, Exeltis, Principal Investigator, Daiichi Sankyo, Speaker, Novo Nordisk, Speaker, Bayer Schering Pharma. JM: Employee, Amgen, Employee, Amgen. CY: Employee, Amgen, Employee, Amgen. CL: Employee, UCB Pharma, Employee, UCB Pharma. SY: Employee, Amgen, Employee, Amgen. AG: Employee, Amgen, Employee, Amgen. Nothing to Disclose: FM, EG