nsitioned to open-label alendronate 70 mg weekly while remaining blinded to their initialtreatment.
This was an event driven trial. The coprimary efficacy endpoints were the incidence of morphometricvertebral fracture at 24 months and time to the first clinical fracture through the primary analysis period,which ended when at least 330 subjects had a clinical fracture and all subjects had completed the24-month visit. Clinical fracture was a composite endpoint of nonvertebral fracture and symptomaticvertebral fracture.
Effect on Fractures
EVENITY significantly reduced the incidence of new vertebral fracture at 24 months (see Table 3).
Table 3 Effect of EVENITY on the Incidence of New Vertebral Fractures in Study 2
Proportion of Women with
Fracture (%) Risk Reduction p-value b
Alendronate
Alone
(N = 2047)
EVENITY
Followed by
Alendronate
(N = 2046)
Absolute Risk
Reduction (%)
(95% CI)a
Relative Risk
Reduction (%)
(95% CI)a
New vertebral fracture
through Month 24 8.0% 4.1% 4.0 (2.5, 5.6) 50 (34, 62) <0.001
N= Number of subjects randomized
a. Absolute and relative risk reductions are based on the Mantel-Haenszel method adjusting for age strata,baseline total hip BMD T-score (≤ -2.5, > -2.5), and presence of severe vertebral fracture at baseline.
b. P-value is based on logistic regression model for new vertebral fracture) adjusting for age strata, baseline totalhip BMD T-score, and presence of severe vertebral fracture at baseline.
EVENITY significantly reduced the risk of clinical fracture through the end of the primary analysisperiod (see Table 4). This was an event-driven trial and the duration of follow-up varied across subjects.
The median duration of subject follow-up for the primary analysis period was 33 months. Subjects withnonvertebral fracture comprised 83% of the subjects with clinical fracture during the primary analysisperiod.
Table 4 Effect of EVENITY on the Risk of Clinical Fractures in Study 2
Proportion of Women with
Fracture (%)a
Hazard Ratio
(95% CI)c
p-valuec
Alendronate Alone
(N = 2047)
EVENITY Followed
by Alendronate
(N = 2046)
Clinical fracture through
primary analysis periodb 13.0% 9.7% 0.73 (0.61, 0.88) <0.001
N= Number of subjects randomized
a. % = number of subjects who had a clinical fracture through the primary analysis period/N*100%; theduration of follow-up varied across subjects.
b. Primary analysis period ended when clinical fracture events were confirmed for at least 330 subjects and allsubjects completed the month 24 study visit. The median duration of follow-up for the primary analysisperiod was 33 months.
c. Hazard ratio and P-value are based on Cox proportional hazards model adjusting for age strata, baseline totalhip BMD T-score, and presence of severe vertebral fracture at baselineEVENITY followed by alendronate also significantly reduced the risk of nonvertebral fracture throughthe primary analysis period (with a median follow-up of 33 months), with a hazard ratio of 0.81 (95% CI:0.66, 0.99; p = 0.04) compared to alendronate alone.
Effect on Bone Mineral Density (BMD)
EVENITY significantly increased BMD at the lumbar spine, total hip, and femoral neck compared withalendronate at month 12. The treatment differences in BMD were 8.7% at the lumbar spine, 3.3% at thetotal hip, and 3.2% at the femoral neck.
Twelve months of treatment with EVENITY followed by 12 months of tr |
