New drug for uterine fibroids! Best-in-class GnRH subject antagonist linzagolix EU applied for listing

Yselty's active pharmaceutical ingredient linzagolix (formerly OBE2109) is a new, oral, daily GnRH-subject antagonist with potential best-in-class characteristics.
, linzagolix is in the late stages of clinical development for the treatment of monthly multiple (HMB) and endometriosis-related pain associated with uterine fibroids.
ObsEva obtained a linzagolix license from Kissei in late 2015 and acquired the global (excluding Asian) commercial rights to the product.
If approved, Yselty will be the only GnRH antagonist with a flexible dose in the treatment of uterine fibroids: (1) 100 mg dose per day for contraindications or tend to avoid hormone-add-back therapy (add -back therapy, ABT) female patients; (2) 200mg combined ABT once a day for long-term use (more than 6 months) ;(3) 200mg per day for short-term use, suitable for short-term use when needed to quickly reduce fibroid volume.
Phase 3 clinical program for Yselty's treatment of uterine fibroids includes 2 key clinical trials (PRIMROSE 1 and PRIMROSE 2).
these studies have met the criteria for success: both low-dose and high-dose linzagolix and unlinked ABT are effective in treating HMB associated with uterine fibroids and have acceptable benefits-risks.
linzagolix chemical structure (Photo: probechem.cn) PRIMROSE 1 trial was conducted in the United States, a total of 574 cases of uterine fibroid female patients;
in both clinical trials, patients were given 100 mg or 200 mg doses of linzagolix (co-usable and unlinked hormone ABT) or a placebo.
two trials had a reduction in HMB in week 24 of treatment, and respondents were defined as patients who were measured with alkaline hemolybin, menstrual blood loss (MBL) ≤80mL and MBL was ≥50% lower than the baseline.
end points include amenomensis, reduced MBL time, hemoglobin (Hb), pain, and quality of life (QoL).
safety endpoints include bone density (BMD) and adverse events (AE).
/vitamin D is not provided during the study period.
bone density was measured by a dual-energy X-ray absorber (DEXA) scan during baseline examination, 24 weeks, 52 weeks, and 76 weeks (assessment six months after treatment).
results showed that both trials had successfully reached the main endpoint: A significant statistical and clinical reduction in HMB in all dose groups compared to placebos.
study found that linzagolix had a clear therapeutic effect-dose-response, with the highest primary endpoint response rate observed in women receiving 200 mg of combined ABT.
all doses improved significantly in terms of secondary endpoints (amenomenia, time for MBL reduction, hemoglobin levels, pain, quality of life) in anemia patients.
and fibroids in the 200 mg dose group decreased rapidly and significantly.
in the PRIMROSE 1 trial, the response rate in the 200mg-ABT group was 75.5% (p<0.001), in the 100mg (no ABT) group was 56.4% (p-0.003) and in the placebo group it was 35.0%.
overall safety conditions were in line with expectations, and the most common adverse events (occurring in more than 5% of patients) were headaches and hot water.
the average percentage change from baseline to BMD, which is consistent with any GnRH antagonist therapy.
in the PRIMROSE 2 trial, the response rate was 93.9% (p<0.001) and 56.7% (p<0.001) in the 200mg-ABT group and 29.4% in the placebo group.
overall safety conditions were in line with expectations, and the most common adverse events (occurring in more than 5% of patients) were headaches and hot water.
percentage change from baseline to BMD is small, which is consistent with previous clinical trials.
52-week results showed that the continuous use of linzagolix therapy was sustainable and effective in reducing HMB, with response rates of 91.6% and 53.2%, respectively, in the 200mg-ABT and 100mg (ABT-free) groups.
addition, small incremental changes were observed in week 52 BMD compared to week 24.
original source: Obseva SA Submits Marketing Authorization application to the European Medicines Agency for YSELTY® (linzagolix) for the Treatment of Women with Uterine Fibroids