Linzagolix found effective in reducing severe menstrual bleeding: Lancet

USA: A new study conducted by Jacques Donnez and colleagues found that linzagolix (100 mg or 200 mg) effectively decreased severe menstrual bleeding in women with uterine fibroids. The findings of this study were published in The Lancet. 

Heavy menstrual flow and accompanying symptoms are frequent non-cancerous neoplasms known as uterine fibroids. One dosage of the oral GnRH receptor antagonist linzagolix, may lessen symptoms related to uterine fibroids. The 52-week, randomized, phase 3 studies known as PRIMROSE 1 and PRIMROSE 2 were carried out in clinics in the USA (PRIMROSE 1), Europe, and the USA (PRIMROSE 2).

Five masked treatments were given to eligible women with heavy menstrual bleeding brought on by uterine fibroid in a 1:1:1:1:1 ratio: placebo, 100 mg of linzagolix daily alone, 100 mg of linzagolix daily with once-per-day hormonal add-back therapy, 200 mg of linzagolix daily alone, or 200 mg of linzagolix daily with once-per-day hormonal add-back therapy. The main outcome was a response at 24 weeks in women who had received at least one treatment dosage and had not met any pre-dosing assessments-based exclusion criteria.

The key findings of this study were:

1. In PRIMROSE 1, 574 women were enrolled between May 2017 and October 2020; 48 of these women dropped out of the study, and 15 were excluded; as a result, 511 women were included in the full analysis set.

2. In PRIMROSE 2, 535 women were enrolled; 24 of these participants did not receive the study drug, and ten participants were excluded; as a result, 501 women were included in the full analysis set.

3. In all studies, all linzagolix treatment groups considerably outperformed the placebo group in the percentage of women who saw a decrease in heavy menstrual bleeding.

4. In PRIMROSE 1, the response rates were 35.0% in the placebo group and 56.4% in the 100 mg group, 66.4% in the 100 mg plus add-back therapy group, 71.4% in the 200 mg group, and 75.5% in the 200 mg plus add-back therapy group.

5. Response rates were 56.7% in the 100 mg group, 77.2% in the 100 mg + add-back therapy group, 77.7% in the 200 mg group, and 93.9% in the 200 mg plus add-back therapy group in PRIMROSE 2, compared to 29.4% with placebo.

"For women who cannot or who choose not to undergo concurrent hormonal add-back therapy, partial suppression with once-daily linzagolix (100 mg) may offer a special alternative for the long-term management of symptomatic uterine fibroids," said the Authors in conclusion.

Reference: 

Donnez, J., Taylor, H. S., Stewart, E. A., Bradley, L., Marsh, E., Archer, D., Al-Hendy, A., Petraglia, F., Watts, N., Gotteland, J.-P., Humberstone, A., & Garner, E. (2022). Linzagolix with and without hormonal add-back therapy for the treatment of symptomatic uterine fibroids: two randomised, placebo-controlled, phase 3 trials. In The Lancet (Vol. 400, Issue 10356, pp. 896–907). Elsevier BV. https://doi.org/10.1016/s0140-6736(22)01475-1