ObsEva‘s linzagolix lessened endometriosis-associated pelvic pain and increased the quality of life of endometriosis patients in a sustained, long-term manner, according to results of the Phase 2b EDELWEISS trial.
Linzagolix (previously known as OBE2109) is an oral treatment consisting of a gonadotropin-releasing hormone (GnRH) receptor antagonist. The therapy blocks the GnRH receptor in the pituitary gland, causing a dose-dependent reduction in estrogen production by the ovaries, which leads to a decrease in pain and heavy menstrual bleeding related to endometriosis, as well as reduction in the growth of endometriosis lesions.
The EDELWEISS, randomized, double-blind, placebo-controlled trial (NCT02778399) assessed the safety and efficacy of linzagolix in 327 women with moderate to severe endometriosis-associated pain.
The participants received one of four linzagolix doses (50 mg, 75 mg, 100 mg, or 200 mg daily) or placebo for 12 weeks.
After the initial treatment, the patients could choose between a 24-week follow-up period without taking any medication or a 28-week extension study. Patients in the extension study received the same dose as the original study, except for the 200 mg and placebo groups, who received 100 mg of the therapy daily.
The results of the extension study showed that 69% of the patients in the 75 mg group and 82% in the 200/100 mg group achieved the primary goal of the study, consisting of a 30% reduction in pelvic pain (menstrual or non-menstrual) over at least 28 days (Overall Pelvic Pain, or OPP).
“We are pleased to report long-term data from the EDELWEISS trial of linzagolix, which show that in patients treated with linzagolix for 52 weeks, pelvic pain response rates are maintained with the 75 mg or the 200 mg dose,” Ernest Loumaye, co-founder and CEO of ObsEva, said in a press release.
Overall, 87.5% of women who took 75 mg of linzagolix daily during the original study reported a sustained reduction in pain after the follow-up period. The value for the 200 mg group was 70.0%; the placebo group, 33.3%.
Bone mineral density (BMD) is often affected by GnRH inhibition. However, the results of the trial showed that the BMD reduction returned to values below 2.2%, which is not considered clinically significant.
“Bone mineral density remains within safe limits. Patients that were followed for six months after treatment completion continue to experience pain control, and showed BMD increase,” Loumaye said.
Linzagolix treatment was also associated with a sustained reduction in constipation, menstrual cramps, and painful intercourse, and with an increase in quality of life.
“These data further support the long-term therapeutic potential of linzagolix and support the currently starting Phase 3 program for the endometriosis indication, as we anticipate initial Phase 3 clinical results later this year from the trial in uterine fibroids,” Loumaye said.
The Phase 3 clinical trial is testing the effects of two doses of the therapy, 75 mg daily, which causes partial inhibition of estrogen production, and 200 mg, which creates a total inhibition of estrogen production, with some add-back estrogen supplementation to avoid a severe BMD reduction.
ObsEva presented the full results of the EDELWEISS trial this month at the American College of Obstetricians and Gynecologists (ACOG) annual meeting in Nashville, Tennessee; and the 5th Congress of the Society of Endometriosis and Uterine Disorders (SEUD) in Montreal, Quebec.