Supported by these positive results, the researchers have selected two doses of the investigative therapy to test further in an upcoming Phase 3 program. One dose will promote full suppression of the hormone estradiol, and one will target only partial suppression.
By binding to GnRH in the pituitary gland, linzagolix is intended to prevent the ovaries from producing estrogen. Unlike other currently marketed GnRH agonists, this new treatment candidate can be tailored to the patient’s individual needs, and it can provide fast symptom relief.
The randomized, double-blind, placebo-controlled EDELWEISS study (NCT02778399) was designed to assess the safety and effectiveness of linzagolix in women with confirmed endometriosis. It enrolled 327 women with moderate to severe endometriosis-associated pain at 64 sites across the United States and Europe.
The study’s primary objective was patient response rate, defined as a reduction in menstrual and non-menstrual pelvic pain of at least 30%, over at least 28 days. Participants were randomized to receive one of four tested doses of linzagolix (50, 75, 100, or 200 mg) or a placebo once daily for 12 weeks.
Blood analysis during the study confirmed that a 75 mg linzagolix dose partially prevented the production of estradiol, and full suppression was achieved at 200 mg.
On average, women treated with the top three doses reached the primary goal, with the best response reported in the group treated with 75 mg of linzagolix (61.5%).
A similar positive response was seen in about 56% of the patients who took linzagolix at 100 mg or 200 mg, and 49.4% of those who took the lowest dose, compared with 34.5% of the women in the placebo group.
The treatment had a dose-dependent effect on reducing menstrual pain. Approximately 78.9% of the patients receiving the 200 mg dose reported a significant reduction, compared with 43.3% in the group who took 50 mg.
Linzagolix also led to a significant reduction in non-menstrual pain when taken at 75 mg and 100 mg, with a response rate of 58.5% and 61.5%, respectively, compared with 37.1% in the placebo group.
When given at doses from 75-200 mg, the treatment was able to significantly and consistently improve constipation and the patient’s general well-being. At the 200 mg dose, it also significantly reduced painful sexual intercourse.
“We believe that these data strongly support the therapeutic potential of linzagolix for improving the condition and well-being of patients suffering from endometriosis. In addition, we believe these data further confirm ObsEva’s vision and product development strategy that a significant proportion of patients will not require full E2 suppression which mandates add-back hormone replacement therapy,” Ernest Loumaye, MD, PhD, co-founder and CEO of ObsEva, said in a press release.
In general, the treatment was found to be safe and well-tolerated. The most common side effect was hot flashes, which happen due to the suppression of estradiol and is in line with the safety profile of other similar therapies.
“Given the tremendous need for new therapies that can treat the large and diverse population of women with endometriosis, it is encouraging to see that linzagolix may be able to offer a range of effective dosing alternatives to suit individual patient needs,” said Hugh Taylor, MD, chair of obstetrics, gynecology and reproductive sciences at the Yale School of Medicine, and chief of obstetrics and gynecology at Yale-New Haven Hospital.
Researchers are continuing the EDELWEISS trial for an additional treatment period of 12 weeks. A complete analysis of the results, which will include bone mineral density evaluation, is expected in the fourth quarter of 2018.
Following completion of the trial, ObsEva intends to seek feedback from regulatory agencies on the design of the Phase 3 clinical trial program by the end of 2018.