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) | ||||||
| > | 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) | ||||||
| > | 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 | 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 | 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 | 3 |
| Mood altered, mood swings | 6 | 5 | 3 |
| Amenorrhea | 4 | 7 | > |
| 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=""> | 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=""> | 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=""> | 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
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
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
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