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Drug Trials Snapshot: EVENITY

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 the EVENITY Package Insert for complete information.

EVENITY (romosozumab-aqqg)
e-ven-i-tee 
Amgen, Inc.
Approval date: April 9, 2019


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

EVENITY is a drug to treat osteoporosis (thinning and weakening of bone) in women after menopause (“change of life”) who:

  • are at high risk of breaking a bone (fracture), or 
  • cannot use another osteoporosis medicine or other osteoporosis medicines did not work well.

How is this drug used?

EVENITY is administered as 2 injections under the skin (subcutaneously) once a month for 12 months.

What are the benefits of this drug?

In Trial 1, patients who received EVENITY had fewer new bone fractures in the spine after 12 months compared to patients who received placebo. Patients who received EVENITY followed by denosumab (another medicine approved to treat osteoporosis) for an additional 12 months also had fewer new bone fractures than patients who received placebo followed by denosumab. 

In Trial 2, patients who received EVENITY for 12 months followed by alendronate (another medicine approved to treat osteoporosis) for 12 months had fewer new bone fractures in the spine compared to patients who received alendronate for 24 months.

What are the benefits of this drug (results of trials used to assess efficacy)?

The tables below summarize efficacy results for clinical Trials 1 and 2 in patients with postmenopausal osteoporosis. The co-primary efficacy endpoints in Trial 1 were new vertebral fractures at month 12 and month 24. The co-primary efficacy endpoints in Trial 2 were the incidence of vertebral fracture at 24 months and the time to the first clinical fracture.

Table 2. Effect of EVENITY on the Incidence and Risk of Fractures in Trial 1

 

 

Proportion of Women with Fractures

Absolute Risk

Reduction

(%)

(95% CI)a

Relative Risk

Reduction

(%)

(95% CI)a

p‑valueb

 

At Month 12

 

Placebo

(N = 3591)

EVENITY

(N = 3589)

 

 

 

 

 

 

New vertebral fracture

1.8%

0.5%

1.3

 (0.8, 1.8)

73

(53, 84)

< 0.001

At Month 24

Placebo

Followed by

denosumab

(N = 3591)

EVENITY

Followed by
denosumab

(N = 3589)

 

 

 

New vertebral fracture

2.5%

0.6%

1.9

(1.3, 2.5)

75

 (60, 84)

< 0.001

N = Number of subjects randomized.  

  1. Absolute and relative risk reduction are based on the Mantel‑Haenszel method adjusting for age and prevalent vertebral fracture strata. 
  2. P‑value is based on logistic regression model adjusting for age and prevalent vertebral fracture strata.

EVENITY Prescribing Information

 

Table 3. Effect of EVENITY on the Incidence of New Vertebral Fractures in Trial 2

 

Proportion of Women with

Fracture (%)

Risk Reduction

p-valueb

 

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

  1. 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. 
  1. P‑value is based on logistic regression model for new vertebral fracture) adjusting for age strata, baseline total hip BMD T‑score, and presence of severe vertebral fracture at baseline.

 

EVENITY Prescribing Information

 

Table 4. Effect of EVENITY on the Risk of Clinical Fractures in Trial 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

  1. % = number of subjects who had a clinical fracture through the primary analysis period/N*100%; the duration of follow-up varied across subjects.
  2. Primary analysis period ended when clinical fracture events were confirmed for at least 330 subjects and all subjects completed the month 24 study visit. The median duration of follow-up for the primary analysis period was 33 months.
  3. Hazard ratio and P-value are based on Cox proportional hazards model adjusting for age strata, baseline total hip BMD T-score, and presence of severe vertebral fracture at baseline

EVENITY 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 limited number of fractures and patients in other races.
  • Age: EVENITY worked similarly in women younger and older than 75 years of age.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The tables below present efficacy results by subgroup in clinical Trials 1 and 2.

 

Table 5. New Vertebral Fracture Through Month 12 by Demographics (Trial 1)

Subgroup

EVENITY

N a =3589

n/N1b (%)

Placebo

N=3591

n/N1 (%)

RRRc (95% CI)

Race

  White

10/1871 (0.5)

40/1870 (2.1)

74 (49, 87)

  Other

6/1450 (0.4)

19/1452 (1.3)

69 (23, 88)

Age

  < 65 years

1/722 (0.1)

12/709 (1.7)

92 (37, 99)

  > 65 years

15/2599 (0.6)

47/2613 (1.8)

68 (43, 82)

  < 75 years

10/2297 (0.4)

39/2309 (1.7)

74 (48, 87)

  > 75 years

6/1024 (0.6)

20/1013 (2.0)

70 (27, 88)

aN=Number of patients randomized

bN1=Number of patients in the primary analysis set for vertebral fractures

cRRR=Relative risk reduction and 95% CI based on the Mantel-Haenszel method adjusted for age strata (when appropriate) and prevalent vertebral fracture (Yes, No) at baseline.

FDA Review

 

Table 6. New Vertebral Fractures Through Month 24 by Demographics (Trial 1)

Subgroup

EVENITY Followed by

Denosumab

N a =3589

n/N1b (%)

Placebo Followed by

Denosumab

N=3591

n/N1 (%)

RRRc (95% CI)

Race

  White

12/1874 (0.6)

54/1874 (2.9)

77 (58, 88)

  Other

9/1451 (0.6)

30/1453 (2.1)

71 (38, 86)

Age

  < 65 years

1/725 (0.1)

16/710 (2.3)

94 (54, 99)

  > 65 years

20/2600 (0.8)

68/2617 (2.6)

70 (51, 82)

  < 75 years

11/2301 (0.5)

56/2312 (2.4)

80 (62, 90)

  > 75 years

10/1024 (1.0)

28/1015 (2.8)

65 (28, 83)

aN=Number of patients randomized

bN1=Number of patients in the primary analysis set for vertebral fractures

cRRR=Relative risk reduction and 95% CI based on the Mantel-Haenszel method adjusted for age strata and prevalent vertebral fracture (Yes, No) at baseline.

FDA Review

 

Table 7. New Vertebral Fracture Through Month 24 by Demographics (Trial 2)

Subgroup

EVENITY Followed by

Alendronate

N a =2046

n/N1b (%)

Alendronate Alone

N=2047

n/N1 (%)

RRRc (95% CI)

Race

  White

61/1278 (4.8)

112/1260 (8.9)

47 (28, 61)

  Other

13/547 (2.4)

35/574 (6.1)

61 (27, 79)

Age

  < 75 years

37/890 (4.2)

61/901 (6.8)

38 (8, 58)

  > 75 years

37/936 (4.0)

86/933 (9.2)

68 (39, 71)

aN=Number of patients randomized

bN1=Number of patients in the primary analysis set for vertebral fractures

cRRR=Relative risk reduction and 95% CI based on the Mantel-Haenszel method adjusted for age strata (when appropriate), baseline total hip BMD T-score (< -2.5, > -2.5) and, presence of severe vertebral fracture at baseline

FDA Review

 

Table 8. Clinical Fracture Through Primary Analysis Period by Demographics (Trial 2)

Subgroup

EVENITY Followed by

Alendronate

N a =2046

n/N1b (%)

Alendronate Alone

N=2047

n/N1 (%)

HRc (95% CI)

Race

  White

156/1447 (10.8)

196/1415 (13.9)

0.8 (0.6, 0.9)

  Other

42/599 (7.0)

70/631 (11.1)

0.6 (0.4, 0.9)

Age

  < 75 years

87/973 (8.9)

115/978 (11.8)

0.8 (0.6, 1.0)

  > 75 years

111/1073 (10.0)

151/1071 (14.1)

0.7 (0.6, 0.9)

aN=Number of patients randomized

bN1=Number of patients in the primary analysis set for vertebral fractures

cHR=Hazard Ratio and 95% CI based on Cox proportional hazards model adjusting forbaseline total hip BMD T-score (< -2.5, > -2.5) and, presence of severe vertebral fracture at baseline

FDA Review

What are the possible side effects?

EVENITY may cause serious side effects including heart attack, stroke or death from a cardiovascular (heart or blood vessel) problem.

 

Other serious side effects include allergic reactions, decreased calcium levels in the blood, jaw problems (osteonecrosis), and unusual thigh bone fractures.

 

The most common side effects of EVENITY are joint pain and headache.

What are the possible side effects (results of trials used to assess safety)?

The table below summarizes adverse reactions in patients with postmenopausal osteoporosis in clinical Trials 1 and 2.

 

Table 9. Adverse Reactions Occurring in ≥ 2% of EVENITY‑treated Women in at least One Trial (Trial 1 and Trial 2)

 

Trial 1

Trial 2

Preferred Term

EVENITY

 (N = 3581)

 n (%)

Placebo

 (N = 3576)

 n (%)

Alendronate

(N = 2014)

n (%)

EVENITY

(N = 2040)

n (%)

Arthralgia

468 (13.1)

434 (12.1)

194 (9.6)

166 (8.1)

Headache

235 (6.6)

208 (5.8)

110 (5.5)

106 (5.2)

Muscle spasms

163 (4.6)

140 (3.9)

81 (4.0)

70 (3.4)

Edema peripheral

86 (2.4)

67 (1.9)

38 (1.9)

34 (1.7)

Asthenia

84 (2.3)

79 (2.2)

53 (2.6)

50 (2.5)

Neck pain

80 (2.2)

54 (1.5)

42 (2.1)

34 (1.7)

Insomnia

72 (2.0)

68 (1.9)

36 (1.8)

34 (1.7)

Paresthesia

72 (2.0)

62 (1.7)

34 (1.7)

29 (1.4)

EVENITY Prescribing Infomation

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. The occurrence of side effects among White and Asian patients was similar. The occurrence of side effects among other races could not be determined because of the limited number of patients in other races. 
  • Age: The occurrence of side effects was similar in women younger and older than 75 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The tables below summarize the occurrence of the most common adverse reaction, arthralgia, by race and age group in clinical Trials 1 and 2.

Table 10. Adverse Reactions of Arthralgia by Race (Trial 1 and Trial 2)

Adverse Event

White

Asian

Black

Other

Control

(N=3467)

n (%)

EVENITY (N=3510)

n (%)

Control

(N=590)

n (%)

EVENITY

(N=562)

n (%)

Control

(N=97)

n (%)

EVENITY

(N=96)

n (%)

Control

(N=1484)

n (%)

EVENITY

(N=1467)

n (%)

Arthralgia

298 (8.6)

325 (9.3)

55 (9.3)

70 (12.4)

27 (27.8)

20 (20.8)

248 (16.7)

219 (14.3)

Control=placebo or alendronate

N=number of patients in the analysis set

n=number of patients reporting > 1 event

Clinical Trial Data

 

Table 11. Adverse Reactions of Arthralgia by Age Group (Trial 1 and Trial 2)

Adverse Event

< 65 years

> 65 – 74 years

> 75 – 84 years

> 85 years

Control

(N=993)

n (%)

EVENITY

(N=1003)

n (%)

Control

(N=2433)

n (%)

EVENITY

(N=2431)

n (%)

Control

(N=1899)

n (%)

EVENITY

(N=1914)

n (%)

Control

(N=265)

n (%)

EVENITY

(N=273)

n (%)

Arthralgia

115 (11.6)

131 (13.1)

269 (11.1)

287 (11.8)

215 (11.3)

191 (10.0)

29 (10.9)

25 (9.2)

Control=placebo or alendronate

N=number of patients in the analysis set

n=number of patients reporting > 1 event

WHO WAS IN THE STUDIES?

Who participated in the clinical trials?

The FDA approved EVENITY based on evidence from two clinical trials of 11273 postmenopausal women with osteoporosis. The trials were conducted in Asia, Canada, Central and Latin America, South America, Europe, Mexico, New Zealand, and the United States.

 

Figure 1 summarizes how many women were enrolled in the clinical trials.

 

Figure 1. Baseline Demographics by Sex

Evenity

 

Figure 2 summarizes the percentage of patients by race in the clinical trials.

 

Figure 2. Baseline Demographics by Race

Evenity Figure 2

 

*Other includes Native Hawaiian or Other Pacific Island, Mixed, Multiple, and Missing

FDA Review


Table 1. Demographics by Race

Race

Number of Patients

Percentage

White

6977

62

Black or African American

193

2

Asian

1152

10

American Indian or Alaska Native

139

1

Native Hawaiian or Other Pacific Islander

3

Less than 1

Other

1454

13

Multiple/Mixed

1354

12

Missing

1

Less than 1

 

FDA Review

 

Figure 3. Baseline Demographics by Age

Evenity Figure 3

 

FDA Review

 

Who participated in the trials?

The table below summarizes demographics of the patients in the combined clinical trials .

 

 Table 12. Baseline Demographics for Trials 1 and 2

 

 

Trial 1

 

 

Trial 2

 

 

 

 

Total

(N=11273)

 

EVENITY

(N=3589)

Placebo

(N=3591)

EVENITY

 (N=2046)

 

Alendronate

(N=2047)

 

Sex - n (%)

     Women

3589 (100.0)

3591 (100.0)

2046 (100)

2047 (100)

11273 (100)

Race - n (%)

White

2063 (57.5)

2052 (57.1)

1447 (70.7)

1415 (69.1)

6977 (61.9)

Asian

425 (11.8)

441 (12.3)

137 (6.7)

149 (7.3)

1152 (10.2)

Black or African American

77 (2.1)

74 (2.1)

19 (0.9)

23 (1.1)

193 (1.7)

American Indian or Alaska native

64 (1.8)

63 (1.8)

5 (0.2)

7 (0.3)

139 (1.2)

Native Hawaiian or Other Pacific Islander

0 (0)

1 (<0.1)

0 (0)

2 (<0.1)

3 (<0.1)

     Multiple/Mixed

623 (17.4)

636 (17.7)

50 (2.4)

45 (2.2)

1354 (12.0)

     Other

337 (9.4)

324 (9.0)

388 (19.0)

405 (18.9)

1454 (12.9)

     Missing

0 (0)

0 (0)

0 (0)

1 (<0.1)

1 (<0.1)

Age Group - n (%)

<65 years

768 (21.4)

757 (21.1)

239 (11.7)

240 (11.7)

2004 (17.8)

> 65 to 74 years

1704 (47.5)

1719 (47.9)

737 (36.0)

758 (37.0)

4918 (43.6)

≥75 years

1117 (31.1)

1115 (31.0)

1070 (52.3)

1049 (51.2)

4351 (38.6)

Age (years)

     Mean (SD)

70.9 (7.0)

70.8 (6.9)

74.4 (7.5)

74.2 (7.5)

72.6 (7.2)

     Median (min., max.)

70.0 (55, 90)

70.0 (55, 90)

75.0 (55, 90)

75.0 (55, 90)

72.0 (55, 90)

Ethnicity - n (%)

Hispanic/Latino

1427 (39.8)

1416 (39.4)

631 (30.8)

662 (32.3)

4136 (36.7)

Not Hispanic/Latino

2162 (60.2)

2175 (60.6)

1415 (69.2)

1385 (67.7)

7137 (63.3)

Geographic Region - n (%)

Central and Eastern Europe and Middle East

1043 (29.1)

1050 (29.2)

835 (40.8)

798 (39.0)

3726 (33.0)

Central/Latin America

1550 (43.2)

1534 (42.7)

674 (32.9)

727 (35.5)

4485 (13.4)

Western Europe and Australia/New Zealand

482 (13.4)

497 (13.6)

269 (13.1)

264 (12.9)

1512 (39.8)

Asia Pacific and South Africa

410 (11.4)

419 (11.7)

213 (10.4)

216 (10.6)

1258 (11.2)

North America

104 (2.9)

91 (2.5)

55 (2.7)

42 (2.1)

292 (2.6)

United States

69 (66.3)

63 (69.2)

33 (1.6)

24 (1.2)

189 (1.7)

Canada

35 (33.7)

28 (30.8)

22 (1.1)

18 (0.9)

103 (0.9)

Clinical Trial Data

How were the trials designed?

The benefits and side effects of EVENITY were evaluated in two clinical trials of postmenopausal women aged 55 to 90 years with osteoporosis. All women took daily calcium and vitamin D supplements.  

 

In Trial 1, women were randomly assigned to receive either EVENITY or placebo as an injection under the skin once monthly for 12 months. Neither the women nor the health care providers knew which treatment was being given. After the initial 12-month treatment period, women in both groups received denosumab (another approved medication for postmenopausal women with osteoporosis) as an injection under the skin once every 6 months for an additional 12 months. The benefit of EVENITY was evaluated by measuring the occurrence of new spine fractures at 12 months and 24 months.

 

In Trial 2, women were randomly assigned to receive either EVENITY as an injection under the skin once monthly or alendronate (another approved medication for postmenopausal women with osteoporosis) once weekly by mouth for 12 months. Neither the women nor the health care providers knew which treatment was being given. After the initial 12-month treatment period, women in both groups received alendronate by mouth through the end of the trial. The benefit of EVENITY was evaluated by measuring the occurrence of new spine fractures through 24 months.  The trial also measured the occurrence of clinical fractures (defined as fractures in bones other than the spine or fractures in the spine that caused symptoms). Clinical fractures were assessed when at least 330 patients had a clinical fracture and all patients completed at least 24 months of the trial.

How were the trials designed?

The efficacy and safety of EVENITY were evaluated in two randomized, double-blind, clinical trials. All patients were postmenopausal women aged 55 to 90 years. All women received daily calcium and vitamin D supplements.

 

Trial 1 was a randomized, double-blind, placebo-controlled trial in women with bone mineral density (BMD) T-scores less than or equal to -2.5 at the total hip or femoral neck. Women were randomized to receive EVENITY 210 mg or placebo subcutaneously (SC) for 12 months. After 12 months, women in both groups received open label denosumab 60 mg SC every 6 months for an additional 12 months. The co-primary efficacy endpoints were new vertebral fractures at month 12 and month 24.

 

Trial 2 was a randomized, double-blind, alendronate-controlled trial.  At baseline, women had one of the following:

  • BMD T-score less than or equal to -2.5 at the total hip or femoral neck and either one moderate or severe vertebral fracture or two mild vertebral fractures
  • BMD T-score less than or equal to -2.0 at the total hip or femoral neck and either two moderate or severe vertebral fractures or a history of a proximal femur fracture.

 

Women were randomized to receive monthly SC injections of EVENITY 210 mg or weekly alendronate 70 mg orally for 12 months. After the initial 12-month treatment period, women in both arms received open-label oral alendronate 70 mg weekly through the end of the trial. The total treatment duration varied for individual patients (the median study duration was 33 months). The co-primary efficacy endpoints were new vertebral fractures at month 24 and the time to the first clinical fracture (composite endpoint of non-vertebral fracture or symptomatic vertebral fracture).  The time to the first clinical fracture was evaluated when at least 330 patients had a clinical fracture and all patients completed at least 24 months of the study.

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.

PRESCRIBING INFORMATION

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