INDICATIONS AND USAGE

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TYMLOS is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, TYMLOS reduces the risk of vertebral fractures and nonvertebral fractures.

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Intended for US Healthcare Professionals

TYMLOS efficacy

Consider TYMLOS first after fracture when your patients’ risk of another is at its highest.

TYMLOS ACTIVE trial study design
Minus

A randomized, multicenter, double-blind, placebo- and active-controlled clinical
trial to study the efficacy of TYMLOS for postmenopausal osteoporosis1,2

Postmenopausal women aged 49-86 years (mean age of 69)

TYMLOS 80 mcg (n=824)

Once-daily subcutaneous injection + supplemental calcium (500 mg to 1000 mg) and vitamin D (400 IU to 800 IU)1

Placebo (n=821)

Once-daily subcutaneous injection + supplemental calcium (500 mg to 1000 mg) and vitamin D (400 IU to 800 IU)1

Teriparatide 20 mcg (n=818)

Open-label active comparator
Once-daily subcutaneous injection + supplemental calcium
(500 mg to 1000 mg) and vitamin D (400 IU to 800 IU)2

Months
6
12
18

Primary efficacy endpoint*:

  • New vertebral fracture

Secondary efficacy endpoints*:

  • Nonvertebral fractures
  • BMD at lumbar spine, total hip, and femoral neck (18 months)†

This study was not designed to provide head-to-head comparative efficacy data and cannot be interpreted as evidence of superiority or noninferiority to
teriparatide.

*TYMLOS vs placebo for primary and secondary efficacy endpoints.
†Comparisons at 6 and 12 months are considered exploratory.

Baseline characteristics

Mean age1
69 years
≥1 prevalent vertebral facture1
24%
≥1 prior nonvertebral facture1
48%
No history of fracture2
37%
Mean T-scores1
Lumbar spine
Total hip
Femoral neck
 
-2.9
-1.9
-2.1
Race1
Caucasian
Asian
Black
Ethnicity3
Hispanic
 
~80%
16%
3%
 
24%

Women were excluded from the study if they had used bisphosphonates within the past 5 years for more than 3
months or Prolia® within the past year.2

BMD=bone mineral density.

TYMLOS vs placebo
Plus

TYMLOS provided significant vertebral and nonvertebral fracture risk reduction at
18 months1

 
18 months1,2*† TYMLOS vs placebo
New Vertebral Fractures
New vertebral
fractures
86% RRR, 3.6% ARR‡
Nonvertebral Fractures
Nonvertebral
fractures
43% RRR, 2.0% ARR§

Primary endpoint: New vertebral fracture incidence was 0.6% (n=690) vs 4.2% with placebo (n=711) (P<0.001) at 18 months.1*||

*Modified ITT population, which includes patients who had both pre- and post-treatment spine radiographs.
†Nonvertebral fractures were measured at 18 months of treatment plus one month without.1
‡P<0.0001.1
§P=0.049; P value based on the log-rank test.
||Primary endpoint.

Cumulative incidence of nonvertebral fractures at 19 months#

(18 months of treatment plus 1 month of follow-up without treatment)2

Chart showing cumulative incidence of nonvertebral fractures at 19 months; Tymlos vs. placebo
Chart showing cumulative incidence of nonvertebral fractures at 19 months; Tymlos vs. placebo
Excluded fractures of the sternum, patella, toes, fingers, skull, and face, and those associated with high trauma.6
#Kaplan-Meier estimates using the ITT population at 19 months.6
**P=0.049 vs placebo. P value based on the log-rank test.6

Increases in BMD achieved with TYMLOS vs placebo at 18 months†

 
Lumbar spine
TYMLOS
9.2††
Placebo
0.5
 
Total hip
TYMLOS
3.4††
Placebo
0.1
 
Femoral neck
TYMLOS
2.9††
Placebo
0.4
 
Lumbar spine
Total hip
Femoral neck
TYMLOS
9.2††
3.4††
2.9††
Placebo
0.5
0.1
0.4
†Nonvertebral fractures were measured at 18 months of treatment plus one month without.1
††P<0.0001 versus placebo.7
View Study Safety Data

See fracture risk results achieved with sequential therapy (transitioning patients to open-label alendronate for up to 24 months).1,4,5‡‡

View Study Design
‡‡Results reported in ITT population, which included patients randomized in the efficacy study; last observation carried forward.

ARR=absolute risk reduction; BMD=bone mineral density; ITT=intent to treat; RRR=relative risk reduction.

Active comparator: New vertebral fracture results
Plus

Vertebral and nonvertebral fracture results, inclusive of TYMLOS and teriparatide (active comparator) vs placebo

This study was not designed to provide head-to-head comparative efficacy data and cannot be interpreted as evidence of superiority or noninferiority to teriparatide.2

Exploratory analyses

New vertebral fracture incidence was 0.8% with teriparatide (n=717) vs 4.2% with placebo (n=711) (P<0.001) at 18 months2*

Cumulative incidence of nonvertebral fractures† at 19 months‡ (18 months of treatment plus 1 month of follow-up without treatment)2

Chart showing cumulative incidence of nonvertebral fractures at 19 months; Tymlos vs. placebo, inclusive of teriparatide
Chart showing cumulative incidence of nonvertebral fractures at 19 months; Tymlos vs. placebo, inclusive of teriparatide
*Modified ITT population, which includes patients who had both pre- and post-treatment spine radiographs.
†Excluded fractures of the sternum, patella, toes, fingers, skull, and face, and those associated with high trauma.6
‡Kaplan-Meier estimates using the ITT population at 19 months.6
§P=0.22 vs placebo.
||P=0.049 vs placebo. P value based on the log-rank test.6

Mean percent change from baseline in BMD at 18 months1-3

 
Lumbar
spine
Total
hip
Femoral
neck
TYMLOS
9.2
3.4
2.9
Placebo
0.5
0.1
0.4
Teriparatide
9.1
2.8
2.3
 
Lumbar spine
TYMLOS
9.2
Placebo
0.5
Teriparatide
9.1
 
Total hip
TYMLOS
3.4
Placebo
0.1
Teriparatide
2.8
 
Femoral neck
TYMLOS
2.9
Placebo
0.4
Teriparatide
2.3

P<0.0001 vs placebo.

ARR=absolute risk reduction; BMD=bone mineral density; ITT=intent to treat; RRR=relative risk reduction.

View Study DesignView Study Safety Data
Extension study design
Plus

The extension study evaluated if the fracture risk reductions and increases in BMD achieved with TYMLOS could be maintained with open-label alendronate4

An open-label follow-up study of postmenopausal women who completed the 18-month efficacy study and enrolled in the extension study4

TYMLOS 80 mcg (n=824)
Once-daily subcutaneous injection + supplemental
calcium (500 mg to 1000 mg) and vitamin D (400 IU
to 800 IU)1
Placebo (n=821)
Once-daily subcutaneous injection + supplemental
calcium (500 mg to 1000 mg) and vitamin D (400 IU
to 800 IU)1
Treatment Discontinued
Alendronate 70 mg, open label (n=558)
Once-weekly oral + supplemental calcium (500 mg
to 1000 mg) and vitamin D (400 IU to 800 IU)1,3
Alendronate 70 mg, open label (n=581)
Once-weekly oral + supplemental calcium (500 mg
to 1000 mg) and vitamin D (400 IU to 800 IU)1,3
Months
18
19
25
43
 
 
6-month analysis completed4

Efficacy endpoints3:

  • Incidence of new vertebral fractures
  • Incidence of nonvertebral fractures
  • Changes in BMD from baseline at the lumbar spine, total hip, and femoral neck

The primary and secondary efficacy endpoints for the extension study were at 25 months. Additional analyses were completed at 43 months. The 43-month data are exploratory endpoints.3

BMD=bone mineral density.

Extension data
Plus

Efficacy results achieved with TYMLOS were maintained with sequential therapy1,5

New vertebral fractures: Risk reduction achieved with TYMLOS was maintained after transitioning to open-label alendronate1

Percentage of postmenopausal women with osteoporosis with new vertebral fractures at 25 and 43 months1,5*

 
25 months
New Vertebral Fractures
New vertebral
fractures
87% RRR,
3.9% ARR†
Nonvertebral Fractures
Nonvertebral
fractures
52% RRR,
2.9% ARR
 
43 months
New vertebral fractures
New vertebral
fractures
84% RRR,
4.7% ARR
Nonvertebral fractures
Nonvertebral
fractures
39% RRR,
3.0% ARR
 
25 months
43 months
New Vertebral Fractures
New vertebral fractures
87% RRR, 3.9% ARR†
84% RRR, 4.7% ARR
Nonvertebral Fractures
Nonvertebral fractures
52% RRR, 2.9% ARR
39% RRR, 3.0% ARR
*TYMLOS or placebo for 18 months, followed by 1 month of no treatment, then up to 24 months of open-label alendronate.4
†P<0.0001.1
Results reported in the modified ITT, which included patients who had both pretreatment and posttreatment spine radiographs.1,5
The primary and secondary efficacy endpoints for the extension study were at 25 months. The 43-month data are exploratory endpoints.3
ARR=absolute risk reduction; ITT=intent to treat; RRR=relative risk reduction.

Primary endpoint: New vertebral fracture incidence with TYMLOS transitioning to open-label alendronate was 0.6% (n=544) vs 4.4% with placebo transitioning to open-label alendronate (n=568) (P<0.001) at 25 months.

New vertebral fracture incidence with TYMLOS transitioning to open-label alendronate was 0.9% (n=544) vs 5.6% with placebo transitioning to open-label alendronate (n=568) (P<0.001) at 43 months (exploratory).

Nonvertebral fractures: Risk reduction achieved with TYMLOS was maintained after transitioning to open-label alendronate5

Cumulative incidence of nonvertebral fractures‡ over 43 months1,3,5§

Chart showing cumulative incidence of nonvertebral fractures over 43 months; Tymlos vs. placebo; 0-18 months: Tymlos and placebo; 19-43 months: open-label alendronate
Chart showing cumulative incidence of nonvertebral fractures over 43 months; Tymlos vs. placebo; 0-18 months: Tymlos and placebo; 19-43 months: open-label alendronate
‡Nonvertebral fractures excluded those of the sternum, patella, toes, fingers, skull, and face, and those associated with high trauma.5
§TYMLOS or placebo for 18 months, followed by 1 month of no treatment, then up to 24 months of open-label alendronate; P value based on the log-rank test.4,5
||P=0.017.1

Results reported in the extension study ITT population, which included patients randomized in the efficacy study.5

The primary and secondary efficacy endpoints for the extension study were at 25 months. The 43-month data are exploratory endpoints.3

BMD increases achieved with TYMLOS were maintained after transitioning to open-label alendronate5

In a 25-month analysis,* significant increases in BMD at the lumbar spine, total hip, and femoral neck achieved with TYMLOS at 18 months were maintained after transitioning to 6 months of open-label alendronate (P<0.0001 at all sites).1

Patients receiving 18 months of TYMLOS maintained at least a two-fold increase in BMD when followed by 24 months of open-label alendronate versus those who transitioned from placebo.1,3

Mean percent change from baseline in BMD in postmenopausal
women with osteoporosis at 43 months3*

 
Lumbar spine
Total hip
Femoral neck
TYMLOS
14.4
6.4
5.3
Placebo
6.5
2.8
1.6

18 months of TYMLOS to 24 months of open-label alendronate (n=558)

18 months of placebo to 24 months of open-label alendronate (n=581)

 
Lumbar spine
TYMLOS
14.4
Placebo
6.5
 
Total hip
TYMLOS
6.4
Placebo
2.8
 
Femoral neck
TYMLOS
5.3
Placebo
1.6

18 months of TYMLOS to 24 months of open-label alendronate (n=558)

18 months of placebo to 24 months of open-label alendronate (n=581)

*TYMLOS or placebo for 18 months, followed by 1 month of no treatment, then up to 24 months of open-label alendronate.1
Results reported in ITT population, which included patients enrolled in the extension study; mean percentage change in BMD was LOCF.3
BMD captured with DXA scans.3
The primary and secondary efficacy endpoints for the extension study were at 25 months. The 43-month data are exploratory endpoints.3
BMD=bone mineral density; DXA=DEXA scan; LOCF=last observation carried forward.
View Study DesignView Study Safety Data
References: 1. TYMLOS [package insert]. Boston, MA: Radius Health, Inc. 2. Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA. 2016;316(7):722-733 [published correction appears in JAMA. 2017;317(4):442]. 3. Data on file. Radius Health, Inc; Boston, MA. 4. Cosman F, Miller PD, Williams GC, et al. 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. Mayo Clin Proc. 2017;92(2):200-210. 5. Bone HG, Cosman F, Miller PD, et al. ACTIVExtend: 24 months of alendronate after 18 months of abaloparatide or placebo for postmenopausal osteoporosis. J Clin Endocrinol Metab. 2018;103(8):2949-2957. 6. Sornay-Rendu E, Boutroy S, Munoz F, Delmas PD. Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res. 2007;22(3):425-433. 7. Gillespie CW, Morin PE. Osteoporosis-related health services utilization following first hip fracture among a cohort of privately-insured women in the United States, 2008-2014: an observational study. J Bone Miner Res. 2017;32(5):1052-1061.