Myfembree continues to demonstrate benefits in women with endometriosis, uterine fibroids

The relugolix combination therapy known as Myfembree provided long-term benefits in women with uterine fibroids and significantly improved daily functioning in women with endometriosis, data from two studies showed.

In May, the FDA approved Myfembree (40 mg relugolix, 1 mg estradiol and 0.5 mg norethindrone acetate, Myovant Sciences) for heavy menstrual bleeding associated with uterine fibroids, the manufacturer said in a press release. The approval was based on data from the phase 3 LIBERTY 1 and LIBERTY 2 trials.

Relugolix combination therapy is also being evaluated among women with endometriosis in the SPIRIT 1 and SPIRIT 2 trials. According to a previous report, endometriosis affects an estimated 170 million women worldwide and up to 10% of women of reproductive age.

Previous data from the SPIRIT trials showed that relugolix combination therapy was well tolerated and associated with a significant reduction in dysmenorrhea and non-menstrual pelvic pain in premenopausal women with endometriosis-associated pain.

The new data on relugolix combination therapy were presented at the American Society for Reproductive Medicine Scientific Congress & Expo.

“These studies provide important new data for relugolix combination therapy, including detailed 2-year efficacy and safety data in women with heavy menstrual bleeding associated with uterine fibroids from the phase 3 LIBERTY studies,” Juan Camilo Arjona Ferreira, MD, the chief medical officer of Myovant Sciences told Healio Primary Care. “They also provide additional insight into the potential effect of relugolix combination therapy in women with pain associated with endometriosis.”

Uterine fibroids

In the first study, Ayman Al-Hendy, MD, PhD, a gynecologist and endoscopic surgeon at the University of Chicago, and colleagues evaluated responses from 238 women with heavy menstrual bleeding stemming from uterine fibroids who previously completed the 24-week LIBERTY trials and the 28-week extension study. They were then randomly assigned in an approximate 1:1 ratio to receive relugolix combination therapy or placebo for 1 year, resulting in a total of 2 years of study participation.

All the women were either in their 30s or 40s, more than 40% were Black and about two-thirds were from North America, according to the researchers.

“We were very happy that we were able to recruit and retain a large number of Black or African American women [since] we know this disease is much more prevalent in women of color,” Al-Hendy said during a presentation.

More participants who received relugolix combination therapy vs. placebo maintained a menstrual blood volume of 80 mL or lower at week 76 (78.4% vs. 15.1% [P < .0001]) and at week 104 (69.8% vs. 11.8% [P < .0001]), according to the researchers. In addition, there was a higher proportion of participants who achieved or maintained amenorrhea in the relugolix combination therapy group compared with the placebo group at week 76 (57.4% vs. 13.3% [P < .0001]) and at week 104 (58.3% vs. 10.6% [P < .0001]).

Women who were randomly assigned to placebo had a higher risk for resuming heavy bleeding compared with those assigned to continue relugolix combination therapy (HR = 0.13; 95% CI, 0.08-0.2), according to Al-Hendy. He reported that participants receiving relugolix combination therapy had an 87% reduced risk for relapse compared with those who were assigned to placebo.

“That’s consistent with the mechanism of action,” Al-Hendy said of the return to heavy bleeding comparison. “This is a short-acting oral antagonist, so we expected the ovulation to return very quickly and hence the bleeding also returned very quickly,”

Previous data have shown that the most common adverse events linked to relugolix combination therapy were hot flash/hyperhidrosis/night sweats, abnormal uterine bleeding, alopecia and decreased libido, according to a Myovant Sciences press release. In the new analysis, two women from each treatment cohort experienced a serious adverse event, and one woman from each cohort stopped taking her respective therapy, Al-Hendy said. However, overall, no new safety signals were detected, he said.

Endometriosis

In the second study, Sawsan As-Sanie, MD, MPH, an associate professor at the University of Michigan Medical Center, and colleagues analyzed Endometriosis Health Profile-30 (EHP-30) pain domain responses from 834 women enrolled in the SPIRIT trials who were randomly assigned in an approximate 1:1 ratio to receive either relugolix combination therapy or placebo daily.

“The EHP-30 pain domain evaluates functional effects of endometriosis-associated pain, with higher scores denoting greater functional impact on pain,” As-Sanie said.

All the women completed the EHP-30 at enrollment in the SPIRIT 1 or the SPIRIT 2 study and again at 24 weeks. The ages of the women ranged from late 20s to early 40s, more than 90% were white and about 20% were from North America. At baseline, the mean overall EHP-30 score was 53.9 among the placebo group and 56.4 among the relugolix combination therapy group.

“Women tended to report severe dysmenorrhea and moderate non-menstrual pelvic pain and dyspareunia at baseline,” As-Sanie said. “Notably at baseline, more than 90% of women reported being moderately significantly or very significantly limited in their daily activities due to endometriosis, as measured by the Patient Global Assessment.”

Among the findings at 24 weeks that favored relugolix combination therapy over placebo were:

• relief from painful periods on the Numeric Rating Scale (74.9% vs. 28.6% [P < .0001]);
• relief from non-menstrual pelvic pain on the Numeric Rating Scale (62.2% vs. 41.1% [P < .0001]);
• frequency in performing daily tasks and activities, such as standing, walking, sleeping and performing chores around the house (33-point change as part of overall EHP-30 score vs. 19.2-point change as part of overall EHP-30 score [P < .0001]);
• feelings of control and power (37.4-point change as part of overall EHP-30 score vs. 22.6-point change as part of overall EHP-30 score [P < .0001]);
• feelings of well being (23.3-point change as part of overall EHP-30 score vs. 14.6-point change as part of overall EHP-30 score [P < .0001]);
• feelings of social support (24.7-point change as part of overall EHP-30 score vs. 15.3-point change as part of overall EHP-30 score [P < .0001]);
• feelings of self-image (23.3-point change as part of overall EHP-30 score vs. 12.2-point change as part of overall EHP-30 score [P < .0001]); and
• overall change in EHP-30 score (29.9-point change as part of overall EHP-30 score vs. 17.7-point change [P < .0001]).

“Clinically meaningful improvements in dysmenorrhea and non-menstrual pelvic pain were reported for the majority of women in both SPIRIT 1 and 2 and were positively correlated with improvements in the EHP-30 pain domain,” As-Sanie concluded.

Next steps

Myovant Sciences and its development and commercialization partner, Pfizer, jointly submitted a supplemental new drug application to the FDA last month that would allow the relugolix combination therapy to be used for “the management of moderate to severe pain associated with endometriosis,” according to the press release. The targeted action date for that application is May 6, 2022.

References:

• Al-Hendy A, et al. Abstract O-5. Presented at: American Society for Reproductive Medicine Scientific Congress & Expo; Oct. 17-20, 2021; Baltimore (hybrid meeting).
• As-Sanie S, et al. Abstract P-118. Presented at: American Society for Reproductive Medicine Scientific Congress & Expo; Oct. 17-20, 2021; Baltimore (hybrid meeting).
• Clinicaltrials.gov. SPIRIT 1: Efficacy and safety study of relugolix in women with endometriosis associated pain. https://clinicaltrials.gov/ct2/show/NCT03204318. Accessed Oct. 26, 2021.
• Clinicaltrials.gov. SPIRIT 2: Efficacy and safety study of relugolix in women with endometriosis-associated pain. https://clinicaltrials.gov/ct2/show/NCT03204331. Accessed Oct. 26, 2021.
• Corte LD, et al. Int J Environ Res Public Health. 2020;doi:10.3390/ijerph17134683.
• Jones G, et al. Obstet Gynecol. 2001;doi:10.1016/S0029-7844(01)01433-8.
• Myovant Sciences and Pfizer present data on Relugolix combination therapy from studies in uterine fibroids and endometriosis at the American Society for Reproductive Medicine Congress. https://investors.myovant.com/news-releases/news-release-details/myovant-sciences-and-pfizer-present-data-relugolix-combination. Published Oct. 19, 2021. Accessed Oct. 25, 2021.