Phase III PRIMROSE 2 trial of KLH 2109 shows benefits in uterine fibroids.- ObsEva SA

ObsEva SA reported positive Phase III trial results from the PRIMROSE 2 trial of KLH 2109 (linzagolix) for the treatment of heavy menstrual bleeding (HMB) due to uterine fibroids. The PRIMROSE 2 trial enrolled 535 women with HMB due to uterine fibroids. The trial was conducted in Europe and the US and evaluated the efficacy and safety of once daily oral linzagolix, including 100 mg and 200 mg doses, both with and without hormonal add-back therapy (ABT).

The primary efficacy endpoint was the reduction in HMB. Responders were defined as patients with menstrual blood loss volume of at most 80 mL and more than 50% reduction from baseline in menstrual blood loss volume at 24 weeks, measured using the alkaline hematin method. Bone mineral density (BMD) was assessed centrally using Dual Energy X-ray Absorptiometry (DEXA) scan at baseline and 24 weeks. The responder rate was 93.9% (p < 0.001) for women receiving 200 mg with ABT and 56.7% for women receiving 100 mg without ABT (p < 0.001), compared to 29.4% in the placebo group. Both doses achieved significant rates of amenorrhea (p < 0.001), reduction in pain (p < 0.001), and improvement in quality of life (p < 0.001). Additionally, significant improvement (p < 0.001) in hemoglobin levels, a reduction in number of days of bleeding and reduction in uterine volume were observed.

Furthermore, a significant reduction in fibroid volume was also observed for the 200 mg dose with ABT (p < 0.008). The overall safety profile was in line with expectations and confirmed that linzagolix was well-tolerated. The most frequently observed adverse events (occurring in > 5% of patients) were headache, hot flushes, and anemia. Mean percentage change from baseline in BMD was consistent with previous clinical data.

Assuming positive results, the company expects that this would lead to a Marketing Authorization Application submission with the European Medicines Agency by year-end 2020 and a New Drug Application submission with the U.S. Food and Drug Administration by Q1 2021.