Drugs

Drug Trials Snapshots: ORILISSA

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 ORILISSA Package Insert for complete information.

ORILISSA (elagolix)
awr-ah-lih-sah
Abbvie, Inc.
Approval date: July 23, 2018


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

ORILISSA is a drug for the treatment of moderate to severe pain associated with endometriosis.

How is this drug used?

ORILISSA is a tablet and is available in two strengths. The lower strength tablet is taken once daily for no more than 24 months. The higher strength tablet is taken twice daily for no more than 6 months. Longer use is not recommended because of bone loss.

What are the benefits of this drug?

Both dose strengths of ORILISSA reduced pain during and between menstrual periods after 3 months of treatment.

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

The tables below summarize efficacy results for the evaluated patients for Trials 1 and 2. The co-primary outcome was the proportion of responders for moderate to severe dysmenorrhea (pain during menstrual periods) and pelvic pain not related to menses (non-menstrual pelvic pain) after 3 months of treatment.

Table 2. Proportion of Responders for Dysmenorrhea and Non-Menstrual Pelvic Pain at Month 3 in Trial 1 and Trial 2, Using the Endometriosis Daily Pain Impact Scale

  Trial 1 Trial 2
ORILISSA Placebo ORILISSA Placebo
150 mg
once daily
N=248
200 mg
twice daily
N=244
N=373 150 mg
once daily
N=221
200 mg
twice daily
N=225
N=353
Dysmenorrhea
Difference from placebo
46%
27%**
76%
56%**
20%
 
43%
21%**
72%
50%**
23%
 
Non-Menstrual Pelvic Pain
Difference from placebo
50%  
14%**
55%  
18%**  
36%
 
50%  
13%**
58%  
21%**
37%
 

Trial 1-1-Dysmenorrhea responder threshold: at least 0.81 point decrease from baseline in dysmenorrhea score; Non-Menstrual Pelvic Pain responder threshold: at least 0.36 point decrease from baseline in Non-Menstrual Pelvic Pain score
Trial 2 - Dysmenorrhea responder threshold: at least 0.85 point decrease from baseline in dysmenorrhea score; Non-Menstrual Pelvic Pain responder threshold: at least 0.43 point decrease from baseline in Non-Menstrual Pelvic Pain score
*p ≤0.01 for test of difference from placebo;
**p≤0.001 for test of difference from placebo

ORILISSA 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 trials were women.
  • Race: The majority of patients in the trials were White. Differences in how well ORILISSA worked among races could not be determined from the information available.
  • Age: Patients in the trials were between 18 and 49 years of age. ORILISSA worked similarly across all age groups tested.

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

The tables below summarize efficacy results by race and age.

Table 3. Proportion of Responders at Month 3 (Primary) for Daily Assessment of Dysmenorrhea by Subgroups – Last Observation Carried Forward (Trial 1)

  ORILISSA 150 mg
once daily
ORILISSA 200 mg
twice daily
Placebo
N % N % N %
Race            
White 220 47 213 78 322 20
Non-White 28 43 31 65 51 20
Age (Years)            
<25 32 41 39 80 51 20
≥ 25 to ≤ 35 156 46 145 74 218 16
>35 60 50 60 78 104 28

FDA Review

Table 4. Proportion of Responders at Month 3 (Primary) for Daily Assessment of Non-menstrual Pelvic Pain by subgroups- Last Observation Carried Forward (Trial 1)

  ORILISSA 150 mg
once daily
ORILISSA 200 mg
twice daily
Placebo
N % N % N %
Race            
White 220 52 213 55 322 37
Non-White 28 39 31 52 51 35
Age (Years)            
<25 32 44 39 44 51 31
≥ 25 to ≤ 35 156 55 145 55 218 34
>35 60 43 60 62 104 43

FDA Review

Table 5. Proportion of Responders at Month 3 (Primary) for Daily Assessment of Dysmenorrhea by Subgroups – Last Observation Carried Forward (Trial 2)

  ORILISSA 150 mg
once daily
ORILISSA 200 mg
twice daily
Placebo
N % N % N %
Race            
White 196 42 203 75 317 23
Non-White 25 52 22 50 36 22
Age (Years)            
<25 25 56 26 65 40 20
≥ 25 to ≤ 35 118 45 109 71 195 22
>35 78 37 90 77 118 25

FDA Review

Table 6. Proportion of Responders at Month 3 (Primary) for Daily Assessment of Non-menstrual Pelvic Pain by Subgroups – Last Observation Carried Forward (Trial 2)

  ORILISSA 150 mg
once daily
ORILISSA 200 mg
twice daily
Placebo
N % N % N %
Race            
White 196 50 203 58 317 36
Non-White 25 48 22 59 36 39
Age (Years)            
<25 25 60 26 50 40 38
≥ 25 to ≤ 35 118 45 109 52 195 34
>35 78 54 90 67 118 41

FDA Review

 

What are the possible side effects?

ORILISSA may cause serious side effects including bone loss, suicidal thoughts or behaviors, worsening of mood including depression and anxiety, menstrual bleeding changes that could make it hard to detect pregnancy, and abnormal liver tests.

ORILISSA may also increase the risk of early pregnancy loss.

The most common side effects are hot flushes and night sweats, headache, nausea, difficulty sleeping, absence of periods, anxiety, joint pain, depression and mood changes.

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

The table below summarizes adverse reactions in endometriosis patients with moderate to severe dysmenorrhea and pelvic pain not related to menses (safety population)./p>

Table 7. Percentage of Patients in Trials 1 and 2 with Treatment-Emergent Adverse Reactions Occurring in at Least 5% of Patients (either ORILISSA Dose Group) and at a Greater Incidence than Placebo

Treatment- Emergent Adverse Reactions ORILISSA
150 mg
once daily
N=475
ORILISSA
200 mg
twice daily
N=477
Placebo N=734
% % %
Hot flushes or night sweats 24 46 9
Headache 17 20 12
Nausea 11 16 13
Insomnia 6 9
Mood altered, mood swings 6 5 3
Amenorrhea 4 7 <1
Depressed mood, depression, depressive symptoms and/or tearfulness 3 6 2
Anxiety 3 5 3
Arthralgia 3 5 3

ORILISSA Prescribing Information

Were there any differences in side effects among sex, race and age?

  • Sex: All patients in the trials were women.
  • Race: The majority of patients in the trials were White. Differences in side effects among races could not be determined from the information available.
  • Age: Patients in the trials were between 18 and 49 years of age. The occurrence of side effects was similar across all age groups tested.

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 reactions by subgroup.

Table 8. Pooled Subgroup Analysis of Hot Flushes (safety population)

Demographic Characteristic ORILISSA 150 mg
once daily
n/N (%)
ORILISSA 200 mg
twice daily
n/N (%)
Placebo
n/N (%)
Race
White 98/419 (23) 193/422 (46) 57/645 (9)
Black or African American 11/44 (25) 16/42 (38) 2/62 (3)
Asian 1/4 (25) 1/3 (33) 1/9 (11)
American Indian/ Alaska Native 0/4 (0) 0/0 (0) 0/4 (0)
Native Hawaiian or Other Pacific 0/1 (0) 1/2 (50) 1/3 (33)
Other 1/3 (33) 3/8 (38) 2/11 (2)
Age Group
< 35 years 78/315 (25) 131/312 (42) 40/471 (9)
> 35 years 33/160 (21) 83/165 (50) 23/263 (9)

Clinical Trial Data

Table 9. Pooled Subgroup Analysis of Headache (safety population)

Demographic Characteristic ORILISSA 150 mg once daily
n/N (%)
ORILISSA 200 mg once daily
n/N (%)
Placebo
n/N (%)
Race
White 69/419 (17) 89/422 (21) 81/645 (13)
Black or African American 9/44 (21) 6/42 (14) 6/62 (10)
Asian 1/4 (25) 0/3 (0) 2/9 (22)
American Indian/ Alaska Native 1/4 (25) 0/0 (0) 0/4 (0)
Native Hawaiian or Other Pacific 0/1 (0) 1/2 (50) 1/3 (33)
Other 0/3 (0) 2/8 (25) 0/11 (0)
Age Group
< 35 years 53/315 (17) 61/312 (20) 43/471 (9)
> 35 years 27/160 (17) 37/165 (22) 47/263 (18)

Clinical Trial Data

Table 10. Pooled Subgroup Analysis of Nausea (safety population)

Demographic Characteristic ORILISSA 150 mg once daily
n/N (%)
ORILISSA 200 mg twice daily
n/N (%)
Placebo
n/N (%)
Race
White 47/419 (11) 69/422 (16) 77/645 (12)
Black or African American 3/44 (7) 6/42 (14) 11/62 (18)
Asian 0/4 (0) 1/3 (33) 1/9 (11)
American Indian/ Alaska Native 1/4 (25) 0/0 (0) 1/4 (25)
Native Hawaiian or Other Pacific 0/1 (0) 0/2 (0) 0/3 (0)
Other 0/3 (0) 2/8 (25) 4/11 (36)
Age Group
< 35 years 42/315 (13) 50/312 (16) 60/471 (9)
> 35 years 9/160 (6) 28/165 (17) 34/263 (9)

Clinical Trial Data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved ORILISSA based on evidence from two clinical trials (NCT01620528/Trial 1 and NCT01931670/Trial 2) of 1686 patients with moderate to severe pain associated with endometriosis. The trials were conducted at 338 sites in Canada, Europe, Latin America, South Africa, and the United States.

Figure 1 summarizes the percentage of patients by sex enrolled in the combined clinical trials used to evaluate efficacy and safety.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many women were in the clinical trial. In total, 1686 (100%) women participated in the clinical trials.

FDA Review

Figure 2 summarizes the percentage of patients by race enrolled in the in the combined clinical trials used to evaluate efficacy and safety.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race enrolled in the clinical trials. In total, 1486 (88%) White, 148 (9%) Black or African American, 16 (1%) Asian, and 36 (2%) Other patients participated in the clinical trials.

FDA Review

Table 1. Demographics of Trials by Race

Race Number of Patients Percentage of Patients
White 1486 88%
Black or African American 148 9%
Asian 16 1%
Other 36 2%

FDA Review

Figure 2 summarizes the percentage of patients by age enrolled in the clinical trials used to evaluate efficacy and safety.

Figure 2. Baseline Demographics by Age

Pie chart summarizing how many individuals of certain age groups were enrolled in the clinical trial. In total, 1686patients (100%) were 18 to 49 years old.

FDA Review

Who participated in the trials?

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

Table 11. Demographic Characteristics for Trials 1 and 2

Demographic Characteristics ORILISSA
150 mg
once daily
N=475
ORILISSA
200 mg
twice daily
N=477
Placebo
N=734
Total
N=1686
Sex
Male 0 0 0 0
Female 475 (100.0) 477 (100.0) 734 (100.0) 1686 (100.0)
Race
White 419 (88.2) 422 (88.5) 645 (87.9) 1486 (88.1)
Black or African American 44 (9.3) 42 (8.8) 62 (8.4) 148 (8.8)
Asian 4 (0.8) 3 (0.6) 9 (1.2) 16 (0.9)
American Indian or Alaska Native 4 (0.8) 0 4 (0.5) 8 (0.5)
Native Hawaiian or Other Pacific 1 (0.2) 2 (0.4) 3 (0.4) 6 (0.4)
Other 3 (0.6) 8 (1.7) 11 (1.5) 22 (1.3)
Age
Mean (SD) 32 + 6 32 + 7 32 + 7 32 + 7
Age Group
18 to 25 years 58 (12.2) 66 (13.8) 95 (12.9) 219 (13.0)
25 to 29 years 104 (21.9) 106 (22.2) 164 (22.3) 374 (22.1)
30 to 34 years 153 (32.2) 140 (29.4) 212 (28.9) 505 (30.0)
35 to 39 years 91 (19.2) 86 (18.0) 143 (19.5) 320 (19.0)
40 to 49 years 69 (14.5) 79 (16.6) 120 (16.3) 268 (15.9)
Ethnicity
Hispanic or Latino 68 (14.3) 73 (15.3) 107 (14.6) 248 (14.7)
Non-Hispanic 407 (85.7) 404 (84.7) 627 (85.4) 1438 (85.3)
Region
United States 355 (74.7) 358 (75.1) 548 (74.7) 1261 (74.8)
Non-United States 120 (25.3) 119 (24.9) 186 (25.3) 425 (25.2)

Clinical Trial Data

How were the trials designed?

The benefit and side effects of ORILISSA were evaluated in two clinical trials. Trials 1 and 2 enrolled patients who had moderate to severe pain associated with endometriosis. Patients were randomly assigned to receive one of two doses of ORILISSA or placebo daily for 6 months. Neither the patients nor the health care providers knew which treatment was being given until after the trial was completed.

Patients rated their pain during and between menstrual periods taking into account whether the pain affected daily activity. Patients used a numerical scale to score how severe the pain was and how much the pain affected their daily activity. The scores for the patients receiving ORILISSA were compared to the scores for the patients who received placebo.

How were the trials designed?

The efficacy and safety of ORILISSA were established in 2 randomized, double-blind, placebo-controlled trials. Trials 1 and 2 evaluated ORILISSA for the treatment of moderate to severe pain associated with endometriosis. Patients were randomized to receive ORILISSA 150 mg once daily, ORILISSA 200 mg twice daily, or placebo for 6 months. The co-primary efficacy endpoints were the proportion of responders for dysmenorrhea and non-menstrual pelvic pain over a 3-month treatment period.

Dysmenorrhea and non-menstrual pelvic pain were evaluated using the Endometriosis Daily Pain Impact Scale. Patients rated their pain severity taking into account its impact on daily activities on a scale from 0 to 3, with higher scores reflecting more severe pain. Patients were considered responders if they had less dysmenorrhea and non-menstrual pelvic pain, and did not use more pain medication.

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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Page Last Updated: 08/13/2018
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