Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend Trial.
OBJECTIVE
To assess the efficacy and safety of 18 months of subcutaneous abaloparatide (ABL-SC) or placebo (PBO) followed by 6 months of alendronate (ALN) (preplanned interim analysis).


METHODS
ACTIVExtend, an extension of ACTIVE, enrolled patients who completed 18 months of ABL-SC or PBO in ACTIVE to receive up to 24 additional months of open-label ALN; there was 1 month between the studies to re-consent patients.


RESULTS
Of 1243 eligible ACTIVE patients, 1139 (92%) were enrolled in ACTIVExtend beginning November 20, 2012. These results are from a prespecified 6-month interim analysis (cutoff date, June 2, 2015); the study is ongoing. Findings indicated percentages of patients with new morphometric vertebral fractures: PBO/ALN, 4.4% vs ABL-SC/ALN, 0.55%; relative risk reduction, 87% (relative risk, 0.13; 95% CI, 0.04-0.41; P<.001). Kaplan-Meier estimated rates of nonvertebral fractures were PBO/ALN, 5.6% vs ABL-SC/ALN, 2.7%; risk reduction, 52% (hazard ratio [HR], 0.48; 95% CI, 0.26-0.89; log-rank P=.02). There was also a 58% risk reduction of major osteoporotic fractures (HR, 0.42; 95% CI, 0.21-0.85; log-rank P=.01) and a 45% risk reduction of clinical fractures (HR, 0.55; 95% CI, 0.33-0.92; log-rank P=.02) in the ABL-SC/ALN group vs the PBO/ALN group. At 25 months, bone mineral density percentage change from ACTIVE baseline for ABL-SC/ALN vs PBO/ALN was as follows: lumbar spine, 12.8%; total hip, 5.5%; femoral neck, 4.5% vs 3.5%, 1.4%, 0.5%, respectively (group differences at all sites P<.001).


CONCLUSIONS
Use of ABL-SC for 18 months followed by ALN for 6 months improved bone mineral density and reduced fracture risk throughout the skeleton and may be an effective treatment option for postmenopausal women with osteoporosis.


BACKGROUND
clinicaltrials.gov Identifier: NCT01657162.
Department of Clinical Medicine, Columbia University, New York, NY; Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY. Electronic address: cosmanf@helenhayeshosp.org.
Felicia
F
Cosman
Colorado Center for Bone Research, Lakewood, CO.
Paul D
PD
Miller
Radius Health Inc, Waltham, MA.
Gregory C
GC
Williams
Radius Health Inc, Waltham, MA.
Gary
G
Hattersley
Radius Health Inc, Waltham, MA.
Ming-Yi
MY
Hu
Center for Clinical and Basic Research, Tallinn, Estonia.
Ivo
I
Valter
Radius Health Inc, Waltham, MA.
Lorraine A
LA
Fitzpatrick
Nordic Bioscience, Copenhagen, Denmark.
Bente Juel
BJ
Riis
Nordic Bioscience, Copenhagen, Denmark.
Claus
C
Christiansen
Columbia University Medical Center, New York, NY.
John P
JP
Bilezikian
University of California at San Francisco School of Medicine.
Dennis
D
Black
D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy*; D058866:Osteoporotic Fractures / Q000209:etiology / Q000517:prevention & control*; D044162:Parathyroid Hormone-Related Protein / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016016:Proportional Hazards Models; D016103:Spinal Fractures / Q000209:etiology / Q000517:prevention & control*
D050071:Bone Density Conservation Agents; D044162:Parathyroid Hormone-Related Protein; C000596789:abaloparatide; D019386:Alendronate