The largest endometriosis Phase 3 study program conducted to date (N=1686)1,2

Summary

Two robust similar multicenter, double-blind, randomized, prospective, placebo-controlled Phase 3 trials of 6-month treatment at 2 doses.

  • 150 mg once daily (lower-dose group).
  • 200 mg twice daily (higher-dose group).

The studies enrolled women with surgically diagnosed endometriosis and moderate or severe endometriosis-associated pain.

Two blinded extension studies were conducted, EM-3 and EM-4, in which the subjects who were originally on ORILISSA in the controlled studies EM-1 and EM-2 were maintained on their dose for an additional 6 months.3 Subjects who were originally on placebo in the controlled studies EM-1 and EM-2 were re-randomized to either ORILISSA 150 mg QD or 200 mg BID dose groups.


ORILISSA 150 mg and 200 mg clinical trial design



ORILISSA was rigorously studied in 2 clinical trials and 2 extension studies with strictly defined endpoints and responses.1-3

Co-primary endpoints1,2

  • Proportion of responders for dysmenorrhea at month 3 compared to placebo.*
  • Proportion of responders for non-menstrual pelvic pain (NMPP) at month 3 compared to placebo.*

*Women were defined as responders only if they experienced clinically meaningful pain reduction and stable/decreased rescue analgesic use for endometriosis-associated pain. Clinically meaningful reduction in pain was defined as a calculated threshold of improvement in pain score in each study. The threshold was determined based on an analysis of the change in pain score that corresponded to “much improved” or “very much improved” on the Patient Global Impression of Change questionnaire.


Select ranked secondary endpoints1,2

  • Change from baseline to Month 6 in dysmenorrhea
  • Change from baseline to Month 6 in non-menstrual pelvic pain
  • Change from baseline to Month 3 in dyspareunia
    • Only participants who were sexually active during the trial were included in the results for dyspareunia

The Daily Endometriosis Pain Impact Scale1,2

ELARIS EM-1 and ELARIS EM-2 asked patients to assess and record their pain and its effect on their activities every day using the Daily Endometriosis Pain Impact Scale. The scale allowed patients to report their pain levels over the previous 24-hour period using the scoring system below, and included a functional component for each score.


Women were defined as responders if they experienced clinically meaningful* pain reduction and stable or decreased rescue analgesic use for endometriosis pain.

*Clinically meaningful reduction in pain was defined as a calculated threshold of improvement in pain score in each study. The threshold was determined based on an analysis of the change in pain score that corresponded to "much improved" or "very much improved" on the Patient Global Impression of Change questionnaire.


Dysnmenorrhea and NMPP


3

Severe


Severe pain. I had great difficulty doing the things I usually do.

Two

Moderate


Moderate discomfort or pain. I had some difficulty doing the things I usually do.

One

Mild


Mild discomfort but I was easily able to do the things I usually do.

Zero

None


No discomfort.




Dyspareunia


3

Severe


I avoided sexual intercourse because of pain.

Two

Moderate


Intercourse was interrupted due to pain.

One

Mild


I was able to tolerate the discomfort during sexual intercourse.

Zero

None


No discomfort during sexual intercourse.

NA


I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse.

Select enrollment criteria and baseline patient characteristics1,2*

  • Premenopausal women (18 to 49 years of age)
  • Moderate/severe dysmenorrhea and non-menstrual pelvic pain
  • Surgically diagnosed (laparoscopy or laparotomy) with endometriosis in the previous 10 years

Select prior therapies5*

At screening, 88% of women reported receiving at least 1 medication for endometriosis related symptoms prior to the trial. The most common previously used medication classes (>15% prevalence) were hormonal contraceptives (49%), anti-inflammatory products (36%), gonadotropin-releasing hormone analogues (26%), and opioids (18%).


Select exclusionary criteria for 6-month extension study enrollment4*

  • The subject decided to withdraw consent for any reason.
  • The subject elected/required surgical intervention for treatment of endometriosis or uterine bleeding, including during the post-treatment follow-up period.
  • The subject became pregnant, or planned to become pregnant in the next 18 months.
  • The subject had BMD decrease ≥8% by DXA at the spine, femoral neck, or total hip.

*This list is not all-inclusive.

>75%

of women who completed the pivotal studies enrolled in the extension studies for an additional 6-month treatment period.6

Selected patient characteristics from ELARIS EM-1 and ELARIS EM-2
(pooled)

Characteristics were consistent across treatment groups and studies


Demographics7

Age, mean (SD) years

32.3 (6.52)



BMI, mean (SD) kg/m2

27.6 (6.48)



Months since surgical diagnosis, mean (SD)

44.3 (34.24)


Baseline8

Baseline use of any analgesics, NSAID and opioid (%)

42.6



Baseline use of analgesics, NSAID only/opioid only (%)

31.3/17.0


Treatment history4

Systemic contraceptives/
GnRH agonist (%)

49.0/25.9

SD = Standard deviation