Effects of Abaloparatide on Vertebral and Non-Vertebral Fracture Incidence in Postmenopausal Women with Osteoporosis - Results of the Phase 3 Active Trial

Presentation Number: LB-OR01-3
Date of Presentation: March 5th, 2015

Paul D Miller*1, Benjamin Zev Leder2, Gary Hattersley3, Edith Lau4, Peter Alexandersen5, Tomas Hala6, Sorica Mustatea7, Bettina Storgaard Nedergaard8, Annesofie Krogsaa9, Jan Slesinger10, Cristiano AF Zerbini11, Ivo Valter12, Zydrune Visockiene13, Beata Jendrych14, Carolina Aguiar Kulak15, Farid Marquez16, Alan G Harris17, Gregory C Williams3, Ming-yi Hu18, Bente Juel Riis19, Luis Augusto Russo20 and Claus Christiansen21
1Colorado Center for Bone Research, Lakewood, CO, 2Harvard Medical School, Boston, MA, 3Radius Health, Inc, Waltham, MA, 4CCBR Hong Kong, China, 5CCBR Vejle, Denmark, 6CCBR Pardubice, Czech Republic, 7CCBR Bucharest, Romania, 8CCBR Aalborg, Denmark, 9CCBR Ballerup, Denmark, 10CCBR Brno, Czech Republic, 11Centro Paulista de Investigação Clinica, São Paulo, Brazil, 12Center for Clinical and Basic Research, Tallinn, Estonia, 13CCBR Vilnius, Lithuania, 14CCBR Warsaw, Warsaw, Poland, 15Federal University of Parana, Curitiba, Brazil, 16Palm Springs Research Center, Hialeah, FL, 17Radius Health, Inc., Waltham, MA, 18Radius Health Inc, Waltham, MA, 19Nordic Biosciences, Copenhagen, Denmark, 20CCBR Rio De Janeiro, Rio de Janiero, Brazil, 21Nordic Bioscience, Copenhagen, Denmark

Abstract

Abaloparatide (ABL) is an investigational osteoanabolic PTHrP analog being developed for the treatment of postmenopausal osteoporosis (PMO). In the ACTIVE double-blind, placebo-controlled (PBO) Phase 3 fracture prevention trial, 2463 PMO women were randomized to receive 18-months of either daily ABL 80-mcg SC, PBO SC or open label teriparatide (TPT) 20-mcg SC. All patients (PTS) received calcium and vitamin D supplements. 2,463 PTS were randomized (ITT population) and 1,901 (77.9%) completed. The groups were well matched for baseline demographics. PTS were 68.8 years old and the mean BMI was 25.1. 16.3% of PTS had 1 vertebral fracture, 28.2% had 2 or more vertebral fractures and 46.8% had at least 1 non-vertebral fracture. The mean spine, femoral neck and total hip baseline T-scores were -2.90, -2.14 and -1.90, respectively. Among the 2,118 PTS who had baseline and post-therapy X-rays, the fracture rate (FR) among those receiving ABL (n=690) was 0.58%, representing a reduction of new incident vertebral FR by 86% as compared to PBO PTS [n=711, FR 4.22%; (p<0.0001)]. The TPT group FR of 0.84% (n=717) was reduced by 80% (p<0.0001 versus PBO). ABL reduced non-vertebral fracture (Kaplan-Meier estimated (KM) FR=2.7%, hazard ratio=0.57, p=0.0489) and clinical fractures (KM FR=3.9%, hazard ratio=0.55, p=0.0112) versus PBO (KM non-vertebral FR=4.7%, KM clinical FR=8.3%). TPT was not significantly different from PBO in non-vertebral fracture (KM FR=3.3%, hazard ratio=0.72, p=0.2157) or clinical fracture (KM FR=4.8%, hazard ratio=0.71, p=0.1127). For wrist fractures ABL (n=824, KM FR 0.5%) and TPT (n=818, KM FR 2.0%) were not were significantly reduced compared to PBO (n=821, KM FR 1.5%); wrist FR was significantly less in ABL than the TPT group (p=0.0149). BMD increased more in ABL and TPT-treated PTS compared to PBO at the spine, femoral neck and hip at 6, 12 and 18 months (p<0.0001 for all comparisons). ABL also increased BMD at the hip at months 6, 12 (both p<0.0001) and 18 (p=0.0003), in the femoral neck at 6, 12 (both p<0.0001) and 18 (p=0.0016) and in the spine at 6 (p<0.0001) and 12 (p=0.0087) significantly more than TPT. ABL was well tolerated the most frequently reported adverse events were back pain, arthralgia, upper respiratory tract infection, hypercalciuria and dizziness. The overall incidence of hypercalcemia (HPC) based on albumin corrected serum calcium measured pre and post injection (4 hours) were 0.37%, 3.41%, and 6.36% for the PBO, ABL and TPT groups, respectively. Both ABL and TPT groups had significantly higher rates of HPC than PBO (p<0.0001), but for ABL was significantly less frequent than for TPT (p=0.0055). These results demonstrate that ABL reduces the incidence and risk of vertebral, non-vertebral, and clinical fractures in in women with PMO and suggest that ABL may prove to be an effective and safe treatment option in the management of PMO.

 

Disclosure: PDM: Principal Investigator, Radius. BZL: Principal Investigator, Radius. GH: Employee, Radius, Employee, Radius. EL: Principal Investigator, Radius. PA: Principal Investigator, Radius. TH: Principal Investigator, Radius. SM: Principal Investigator, Radius. BSN: Principal Investigator, Radius. AK: Principal Investigator, Radius. JS: Principal Investigator, Radius. CAZ: Principal Investigator, Radius. IV: Principal Investigator, Radius. ZV: Principal Investigator, Radius. BJ: Principal Investigator, Radius. CAK: Principal Investigator, Radius. FM: Principal Investigator, Radius. AGH: Employee, Radius, Employee, Radius. GCW: Employee, Radius, Employee, Radius. MYH: Employee, Radius, Employee, Radius. BJR: Collaborator, Radius. LAR: Collaborator, Radius. CC: Collaborator, Radius.