eceived placebo. The cumulative 25-month efficacy dataset included 18 months of exposure to TYMLOS or placebo in Study 003, 1 month of no treatment, followed by 6 months of alendronate therapy in Study 005.
Effect on New Vertebral Fractures
The primary endpoint was the incidence of new vertebral fractures in patients treated with TYMLOS compared to placebo. TYMLOS resulted in a significant reduction in the incidence of new vertebral fractures compared to placebo at 18 months (0.6% TYMLOS compared to 4.2% placebo, p ˂0.0001). The absolute risk reduction in new vertebral fractures was 3.6% at 18 months and the relative risk reduction was 86% for TYMLOS compared to placebo (TABLE 2). The incidence of new vertebral fractures at 25 months was 0.6% in patients treated with TYMLOS then alendronate, compared to 4.4% in patients treated with placebo then alendronate (p ˂0.0001). The relative risk reduction in new vertebral fractures at 25 months was 87% for patients treated with TYMLOS then alendronate, compared to patients treated with placebo then alendronate, and the absolute risk reduction was 3.9% (TABLE 2).
Table 2: Percentage of Postmenopausal Women with Osteoporosis with New Vertebral Fractures (modified Intent to Treat population)*†
* Includes patients who had both pre- and post-treatment spine radiographs in Study 003
† Includes patients who had both pre- and post-treatment spine radiographs in Study 005
‡ Confidence Interval
Percentage of Postmenopausal
Women With Fractures Absolute Risk
Reduction (%)
(95% CI‡) Relative Risk
Reduction (%)
(95% CI‡)
TYMLOS
(N=690*)
(%) Placebo
(N=711*)
(%)
0-18 months 0.6 4.2 3.6
(2.1, 5.4) 86
(61, 95)
TYMLOS/
Alendronate
(N=544†)
(%) Placebo/
Alendronate
(N=568†)
(%)
0-25 months 0.6 4.4 3.9
(2.1, 5.9) 87
(59, 96)
Effect on Nonvertebral Fractures
TYMLOS resulted in a significant reduction in the incidence of nonvertebral fractures at the end of the 18 months of treatment plus 1 month follow-up where no drug was administered (2.7% for TYMLOS-treated patients compared to 4.7% for placebo-treated patients). The relative risk reduction in nonvertebral fractures for TYMLOS compared to placebo was 43% (logrank test p = 0.049) and the absolute risk reduction was 2.0%.
Following 6 months of alendronate treatment in Study 005, the cumulative incidence of nonvertebral fractures at 25 months was 2.7% for women in the prior TYMLOS group compared to 5.6% for women in the prior placebo group (FIGURE 2). At 25 months, the relative risk reduction in nonvertebral fractures was 52% (logrank test p = 0.017) and the absolute risk reduction was 2.9%.
Figure 2. Cumulative Incidence of Nonvertebral Fractures* Over 25 Months (Intent to Treat Population)†
Figure 2
* Excludes fractures of the sternum, patella, toes, fingers, skull and face and those associated with high trauma.
† Includes patients randomized in Study 003
TYMLOS demonstrated consistent reductions in the risk of vertebral and nonvertebral fractures regardless of age, years since menopause, presence or absence of prior fracture (vertebral, nonvertebral) and BMD at baseline.
Effect on Bone Mineral Density (BMD)
Treatment with TYMLOS for 18 months in Study 003 resulted in significant increases in BMD compared to placebo at the lumbar spine, to |
