Drug Trial Snapshot: TYMLOS
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to TYMLOS Prescribing Information for complete information.
TYMLOS (abaloparatide)
(tim lows’)
Radius Health, Inc.
Approval date: April 28, 2017
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
TYMLOS is a drug for the treatment of postmenopausal women with osteoporosis who are at high risk for bone fracture.
How is this drug used?
TYMLOS is an injection that is administered once a day under the skin (subcutaneously).
What are the benefits of this drug?
Patients who received TYMLOS had fewer new bone fractures compared to placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes the efficacy results from the trial based on the incidence of new vertebral fractures in patients treated with TYMLOS compared to placebo.
Table 2. Percentage of Postmenopausal Women with Osteoporosis with New Vertebral Fractures (modified Intent to Treat population)*†
| 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) |
* Includes patients who had both pre- and post-treatment spine radiographs in the Trial
† Includes patients who had both pre- and post-treatment spine radiographs in the trial extension
‡ Confidence Interval
TYMLOS Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: All patients in the trial were women; therefore, differences in how well the drug worked between sexes could not be determined.
- Race: Most of the patients were White. Differences in bone fractures among races could not be determined because of the small number of patients in other races.
- Age: TYMLOS worked similarly in all age groups studied.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The figure below summarizes responses to TYMLOS by race, age subgroups and region. These analyses are exploratory and therefore should be interpreted with caution.
Figure 4. Forest Plot of Relative Risk Ratios of New Vertebral Fractures for TYMLOS Compared to Placebo by Subgroup
FDA Statistical review
What are the possible side effects?
TYMLOS may increase the risk for bone cancer. This is based on animal studies only.
Serious side effects of TYMLOS include a drop in blood pressure upon standing and an increase in blood and urine calcium that may increase the chance of developing kidney stones.
The most common side effects of TYMLOS are an increase in urine calcium, dizziness, nausea, headache, fast heartbeat, fatigue, and upper belly pain.
What are the possible side effects (results of trials used to assess safety)?
The table below summarizes the most common adverse reactions that were reported in the trial.
Table 6. Common Adverse Reactions Reported in Postmenopausal Women with Osteoporosis*
|
|
TYMLOS |
Placebo |
|---|---|---|
|
Hypercalciuria |
11 |
9 |
|
Dizziness |
10 |
6 |
|
Nausea |
8 |
3 |
|
Headache |
8 |
6 |
|
Palpitations |
5 |
0.4 |
|
Fatigue |
3 |
2 |
|
Abdominal pain upper |
3 |
2 |
|
Vertigo |
2 |
2 |
* Adverse reactions reported in ≥2% of TYMLOS-treated patients.
TYMLOS Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: All patients in the trial were women; therefore, differences in side effects between sexes could not be determined.
- Race: Most of the patients were White. Differences in side effects among races could not be determined because of the small number of patients in other races.
- Age: The occurrence of side effects was similar in all age groups studied.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Tables below summarize the occurrence of adverse events and some of the adverse reactions of interest by race and age subgroups. These analyses are exploratory and therefore should be interpreted with caution.
Table 7. Subgroup Analysis by Race
| TYMLOS N=822 |
Placebo N=820 |
|||
|---|---|---|---|---|
| White N=661 n (%) |
Asian N=128 n (%) |
White N=654 n (%) |
Asian N=131 n (%) |
|
| Any adverse event | 584 (88.4) | 124 (96.9) | 564 (86.2) | 123 (93.9) |
| Severe adverse events | 49 (7.4) | 5 (3.9) | 55 (8.4) | 3 (2.3) |
| Serious adverse events | 57 (8.6) | 22 (17.2) | 71 (10.9) | 17 (13.0) |
| Hypercalcemia | 7 (1.1) | 4 (3.1) | 2 (0.3) | 0 |
| Hypercalciuria | 52 (7.9) | 39 (30.5) | 31 (4.7) | 41 (31.3) |
Table 7. Subgroup Analysis by Age
| TYMLOS N=822 |
Placebo N=820 |
|||||
|---|---|---|---|---|---|---|
| <65> N=153 n (%) |
65 to <75> N=518 n (%) |
≥75 yr N=151 n (%) |
<65> N=162 n (%) |
65 to <75> N=514 n (%) |
≥75 yr N=144 n (%) |
|
| Any adverse event | 129 (84.3) | 465 (89.8) | 141 (93.4) | 135 (83.3) | 454 (88.3) | 129 (89.6) |
| Severe adverse events | 6 (3.9) | 37 (7.1) | 11 (7.3) | 15 (9.3) | 30 (5.8) | 15 (10.4) |
| Serious adverse events | 9 (5.9) | 52 (10.0) | 19 (12.6) | 17 (10.5) | 50 (9.7) | 23 (16.0) |
| Hypercalcemia | 2 (1.3) | 7 (1.4) | 2 (1.3) | 2 (1.2) | 1 (0.2) | 0 |
| Hypercalciuria | 15 (9.8) | 63 (12.2) | 15 (9.9) | 7 (4.3) | 53 (10.3) | 14 (9.7) |
Clinical trial data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved TYMLOS based on evidence from one clinical trial of 1645 postmenopausal women with osteoporosis. The trial was conducted in North and South America, Europe and Asia.
The figure below summarizes patients who participated in the trial by sex.
Figure 1. Baseline Demographics by Sex
FDA Statistical review
Figure 2 and Table 1 below summarize the percentage of patients by race.
Figure 2. Baseline Demographics by Race
FDA Statistical review
Table 1. Baseline Demographics by Race
|
Race |
Number of Patients |
Percentage |
|---|---|---|
|
White |
1318 |
80 |
|
Black or African American |
49 |
3 |
|
Asian |
259 |
16 |
|
Other |
19 |
1 |
In total, 1318 Whites (80%), 259 Asians (16%), 49 Black or African Americans (3%) and 19 Other (1%), participated in the clinical trial.)
FDA Statistical review
Figure 3. Baseline Demographics by Age
FDA Statistical review
Who participated in the trials?
The tables below summarize the demographics of patients in the clinical trial.
Table 8. Baseline Demographics
| Parameter | TYMLOS (N=824) n (%) |
Placebo( N=821) n (%) |
Total (N=1645) n (%) |
|---|---|---|---|
| Sex | |||
| Women | 824 (100) | 821 (100) | 1645 (100) |
| Age | |||
| Median (years) | 68 | 68 | 68 |
| Min, max (years) | 49, 85 | 50, 86 | 49, 86 |
| Age Group | |||
| < 65=""> | 152 (18) | 161 (20) | 313 (19) |
| 65 to <75> | 517 (63) | 512 (62) | 1029 (63) |
| ≥ 75 years | 155 (19) | 148 (18) | 303 (18) |
| Race | |||
| White | 663 (81) | 655 (80) | 1318 (80) |
| Black or African American | 26 (3) | 23 (3) | 49 (3) |
| Asian | 128 (16) | 131 (16) | 259 (16) |
| Other | 7 (1) | 12 (2) | 19 (1) |
| Ethnicity | |||
| Hispanic or Latino | 199 (24) | 199 (24) | 398 (24) |
| Not Hispanic or Latino | 625 (76) | 622 (76) | 1247 (76) |
| Region | |||
| North America | 17 (2) | 13 (2) | 30 (2) |
| South America | 222 (27) | 217 (24) | 439 (27) |
| Europe | 460 (56) | 461 (56) | 921 (56) |
| Asia | 125 (15) | 130 (16) | 255 (16) |
Adapted from FDA Statistical Review
How were the trials designed?
There was one trial that evaluated the benefit and side effects of TYMLOS. All patients were women with osteoporosis who took daily calcium and vitamin D supplements.
In the trial, patients were randomly assigned to receive either TYMLOS or placebo injection under the belly skin once daily, for 18 months. Neither the patients nor the health care providers knew which treatment was being given until after the trial was completed.
The benefit of TYMLOS was evaluated by measuring the occurrence of new spine fractures in patients treated with TYMLOS in comparison to placebo during 18 months of treatment.
After the benefit was measured, some of the patients who were previously treated with TYMLOS and some who were previously treated with placebo received alendronate (another approved medication for postmenopausal women with osteoporosis) with calcium and vitamin D supplements for 6 months. The benefit of TYMLOS was further evaluated by measuring the occurrence of new spine fractures up until this 6 month time point (a total of 25 months since first starting TYMLOS or placebo).
How were the trials designed?
The assessment of efficacy and safety of TYMLOS was primarily evaluated in a single, randomized, multicenter, double blind, placebo-controlled clinical trial in postmenopausal women. Patients had osteoporosis and took calcium and vitamin D supplements daily. They were randomized to receive TYMLOS 80 mcg or placebo given subcutaneously once daily for 18 months.
The primary efficacy endpoint was the x-ray incidence of new vertebral fractures in patients treated with TYMLOS compared to placebo.
The trial had an open label extension where patients were no longer receiving TYMLOS or placebo but were maintained in their original randomized treatment group and received 70 mg of alendronate weekly, with calcium and vitamin D supplements for 6 months. The trial measured the cumulative incidence of new vertebral fractures at this 6-month time point, which was 25 months after patients first started TYMLOS or placebo.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.