ObsEva SA's linzagolix reduced heavy menstrual bleeding in women with uterine fibroids compared to placebo, meeting the main goal of a late-stage study.
However, the phase 3 trial called Primrose 2 primarily recruited patients in Europe, resulting in a lower percentage of African American patients, who are disproportionately affected by uterine fibroids.
Linzagolix is the third therapy of its kind to be developed for uterine fibroids, after AbbVie Inc.'s Orilissa, or elagolix, and Myovant Sciences Ltd.'s relugolix, both of which have been shown to reduce women's bleeding. Linzagolix, elagolix and relugolix are all gonadotropin-releasing hormone, or GnRH, antagonists.
According to ObsEva executives, linzagolix is the first uterine fibroids drug candidate to be tested in two drug doses: 100 milligrams without additional hormone therapy called add-back therapy, or ABT, and 200 milligrams with ABT. The 100-milligram dose without ABT could potentially be a first-line treatment for many uterine fibroids patients who do not want to or cannot take ABT, analysts noted. Conditions such as obesity, hypertension and lipid disorders can affect a patient's ability to take ABT.
Executives also said during a Dec. 9 call that linzagolix's 200-milligram dose demonstrated best-in-class efficacy results, compared to those of elagolix and relugolix.
ObsEva's stock was trading down by approximately 13.6% to $3.95, as of 11:11 a.m. ET on Dec. 9.
Still, Leerink analyst Ami Fadia said the Primrose 2 results are "as close to the best-case scenario," and could make linzagolix the best GnRH antagonist drug so far.
Primrose 2 results
In the Primrose 2 trial, linzagolix was evaluated in 535 women for 24 weeks against placebo, with some patients receiving ABT. At week 24, about 94% of women receiving the 200-milligram dose plus ABT, and about 57% of women getting the 100-milligram dose but no ABT reported a significant reduction in menstrual blood loss, meeting the trial's primary goal. In the placebo arm, 29% of patients had a reduction in blood loss.
Linzagolix improved hemoglobin levels, reduced period-related pain, reduced the number of days of bleeding and allowed some women in the trial to skip their periods, meeting secondary goals in both treatment doses, ObsEva said in its Dec. 9 press release. The higher 200-milligram dose group of the trial also saw a reduction in the volume of fibroids.
Uterine fibroids is responsible for the majority of hysterectomy procedures — the removal of one's uterus — in the U.S., according to Yale School of Medicine professor of obstetrics, gynecology and reproductive sciences, Hugh Taylor. Uterine fibroids, characterized by heavy menstrual bleeding and resulting anemia, pain and decreased quality of life, is more common in African Americans.
However, ObsEva's Primrose 2 trial enrolled 95% Caucasian women and 5% black or African American women, as most of the trial sites were in Europe, said ObsEva Chief Medical Officer Elizabeth Garner.
During the call, Leerink's Fadia questioned the high proportion of white participants and whether this contributed to the trial's strong efficacy results, especially as Primrose 2 scored higher on its primary goal compared to trials conducted for AbbVie's and Myovant's therapies.
Garner noted that patients in ObsEva's trial had comparable disease severity to the competing trials. But the executive acknowledged that differences in body mass index, or BMI, may be more relevant in the differing regional and racial and ethnic populations across trials, particularly in the safety results of bone mineral density loss.
Among 367 women with bone mineral density data in Primrose 2, 2.5% of women saw bone loss greater than 8%. The U.S. Food and Drug Administration set 8% as a safety threshold for bone mineral density loss on Orilissa's drug label when the drug was approved for endometriosis, Garner said. According to Orilissa's label, the medicine causes bone mineral density loss that increases with duration of use.
According to Garner, trials for elagolix and relugolix enrolled a substantially greater proportion of African American women, who are less likely to show bone mineral density loss. Garner said the average BMI in Primrose 2 was about 27, while AbbVie's and Myovant's trials had an average BMI of about 32. A higher BMI can translate to higher resistance to bone mineral density loss, ObsEva CEO Ernest Loumaye said.
Primrose 2 is ongoing, with treatment extending to 52 weeks. ObsEva expects to have the full data analysis, including a breakdown of bone mineral density loss by treatment group, in mid-2020. Primrose 1, ObsEva's U.S.-specific phase 3 trial that will provide more data on black or African American women, is also expected to read out in the second quarter of 2020.
ObsEva plans to seek approval for linzagolix in the EU and U.S. by the first quarter of 2021, Loumaye said.
Linzagolix is also being evaluated for endometriosis.