Linzagolix maintains long-term benefit in women with uterine fibroids

Linzagolix treatment continues to reduce menstrual blood loss (MBL) and pain severity, while improving haemoglobin (Hb) level and quality of life (QoL) up to 52 weeks in women with uterine fibroids, according to two phase III randomized clinical trials presented at ESHRE 2021.

The PRIMROSE 1* (P1) and PRIMROSE 2** (P2) cohorts consisted of 526 (mean age 41.6 years) and 511 (mean age 42.9 years) premenopausal women, respectively, with heavy menstrual bleeding (80 mL/cycle MBL) due to uterine fibroids. Participants were randomized to receive placebo, linzagolix 100 mg alone or with hormonal add-back therapy (ABT)***, or linzagolix 200 mg alone or with ABT. After the 24-week treatment period, majority of the subjects continued the same regimen, except for the placebo and linzagolix 200 mg alone groups in P2 who were switched to linzagolix 200 mg with ABT, while the placebo group in P1 continued on placebo until 52 weeks. [ESHRE 2021, abstract O-0135]

In both P1 and P2 cohorts, patients treated with linzagolix 100 mg alone achieved an approximately 50–60 percent decrease in MBL and those treated with linzagolix 100 mg with ABT and linzagolix 200 alone or with ABT demonstrated an 80–90 percent decrease in MBL.

These reductions in menstrual bleeding were seen as early as weeks 4–8 and were maintained through week 52, said lead author Dr Hugh Taylor from Yale School of Medicine in New Haven, Connecticut, US.

All linzagolix treatment groups showed continued improvement in pain scores, Hb level, and health-related QoL throughout the 52-week treatment period.

At week 52, patients who received linzagolix 100 mg alone, 100 mg with ABT, 200 mg alone, or 200 mg with ABT had a greater reduction in pain scores from baseline than those who received placebo in P1 (-3.3, -2.7, -2.6, and -3.9, respectively vs -0.4) and P2 (-2.6, -2.6, -3.0, -2.8 vs -0.4).

Patients treated with linzagolix also achieved a better QoL, as shown by a greater increase in UFS-QoL⁺ symptom severity score, at 52 weeks than those treated with placebo (mean change from baseline, 25.0, 34.2, 29.7, 38.3 [in P1] and 16.8, 29.6, 31.9, and 30.7 [in P2] for 100 mg alone, 100 mg with ABT, 200 mg alone, or 200 mg with ABT, respectively vs 14.6).

Of note, a slightly better response was noticeable with either dose of linzagolix with ABT than linzagolix 100 mg alone, Taylor said.

Among subjects with anaemia (defined as Hb level of <12 g/dL), a mean increase in Hb level, thus reducing the chance of developing anaemia, was seen across all linzagolix dose groups, for 100 mg alone or with ABT (1.7 and 1.9 g/dL [in P1] and 1.2 and 2.9 g/dL [in P2], respectively vs 0.6) and linzagolix 200 mg alone or with ABT (2.2 and 2.7 g/dL [in P1] and 2.4 and 3.0 g/dL [in P2] vs 0.6) compared with the placebo group.

“In conclusion, [once-daily treatment with either dose of] linzagolix … provided a sustained benefit [at 52-week study period that showed] significant reduction in MBL … and improvements in secondary endpoints of haemoglobin, pain, and QoL,” said Taylor.

“Importantly, linzagolix 100 mg without ABT showed good efficacy and is a unique treatment option, the only drug in this class being developed without ABT, … for women who have a contraindication to ABT or who prefer to avoid additional hormones,” he added.

*PRIMROSE 1: Efficacy and safety of OBE2109 in subjects with heavy menstrual bleeding associated with uterine fibroids

**PRIMROSE 2: Efficacy and safety of OBE2109 in subjects with heavy menstrual bleeding associated with uterine fibroids

***ABT: 1 mg oestradiol and 0.5 mg norethindrone acetate

⁺UFS-QoL: Uterine Fibroid Symptom and Quality of Life