backJuly 6, 2020
Positive Results from Uterine Fibroids Phase-III Clinical Trials (PRIMROSE 1 and PRIMROSE 2) of Linzagolix
Kissei Pharmaceutical Co., Ltd. (Head Office: Matsumoto, Nagano; Chairman and CEO: Mutsuo Kanzawa) announced that the GnRH antagonist "Linzagolix (KLH-2109/ OBE2109)" that was discovered in Kissei and licensed out to ObsEva SA (main office, Geneva, Switzerland ,CEO: Dr. Ernest Loumaye) has had the results of the 2 phase III clnical trials for uterine fibroids (PRIMROSE 1 and PRIMROSE 2) released by ObsEva on July 9, 2020 CET.
The results released are the 24-week primary endpoint results of PRIMROSE 1 and the 52-week results of PRIMROSE 2.
PRIMROSE 1 has been conducted in the US with 526 patients, and PRIMROSE 2 has been conducted in US and EU with 535 patients. The efficacy of Linzagolix 100 mg or 200 mg once daily, or each dose with Add-back Therapy (ABT) has been compared to placebo. The primary endpoint is the "responder rate at 24 weeks of menstrual blood loss of ≤80 mL and a ≥50% reduction from baseline".
In PRIMROSE 1, the responder rate of the 24-week primary endpoint was 56.4% (P=0.003) and 75.5% (P<0.001) for 100mg without ABT and 200mg with ABT respectively. Each showed statistically significant improvement in comparison to placebo, and each showed improvement in clinically important secondary endpoints such as reduction in pain, improvement of anemia and QOL. In the safety results, the incidence of adverse events were similar in the Linzagolix and placebo arms. The incidence rate of adverse events >5% were headache and hot flushes. The BMD loss at lumbar spine from baseline to week-24 was a minimal mean percentage change.
The effect of the responder rate of PRIMROSE 2 at week-52 long-term treatment was 53.2% and 91.6% for 100mg without ABT and 200mg with ABT respectively. The efficacy of Linzagolix has been sustatined from the 24-week results. Adverse events of incidence rate of >5% were headache, hot flush and anemia. A smaller incremental change in BMD loss at lumber spine was observed at week-52 compared to week-24. These results demonstrated that it is well tolerated.
The overall responder rate for primary endpoint at week 24 of the pooled data from the 2 Phase 3 studies were 56.6% and 84.7% for 100mg without ABT and 200mg with ABT. This supports that Linzagolix has a profile with a potential to become the best-in-class as the GnRH antagonists.
With the results of the 2 studeis, ObsEva will be submitting for regulatory approval to the EU in 2020 Q4 and US in first half of 2021 for uterine fibroid.
For details on the announcements of ObsEva, please refer to the press release on the website of the company.
https://www.obseva.com/press-releases/
These clinical results have negligible effects on Kissei's consolidated business forecasts for the fiscal year ending in March 2021.
《Reference》
About Linzagolix (KLH-2109):
Linzagolix is a novel, orally administered GnRH receptor antagonist. Linzagolix acts by binding to and blocking the GnRH receptor in the pituitary gland, ultimately reducing estrogen production by the ovaries. In November 2015, Kissei lincesed out exclusive rights to develop and market in countries excluding part of Asia such as Japan to ObsEva. ObsEva is now conducting phase 3 clinical trials for the indications of uterine fibroids and endomteriosis. For uterine fibroids, 2 placebo controlled double-blinded comparison studies (PRIMROSE 1 and 2) are being conducted for patients with heavy menstrual bleeding.
About Phase 3 clinical trials for uterine fibroid (PRIMROSE studies):
PRIMROSE 1 and PRIMROSE 2 are randomized double-blinded placebo controlled Phase 3 trials where the efficacy and safety of Linzagolix 100mg and 200mg with and without ABT have been studied on patients with heavy menstrual bleeding related with uterine fibroid. PRIMROSE 1 has been conducted in the US with 526 women, whilst PRIMROSE 2 has been conducted in the US/ EU with 535 women registered. Both studies have a treatment period of 12 months and follow-up period of 6 months. Calcium and vitamin D supplements have been forbidden to be used by patients for both studies. In Dec 2019, ObsEva released the 24-week interim results of PRIMROSE 2.
About Add-back Therapy:
Hormonal Add-back therapy (ABT), estradiol 1mg /Norethisterone 0.5mg, is treatment of exogenous estrogen replacement to prevent excessive estrogen reduction with the drugs. It reduces the side effects such as bone mineral density loss while maintaining the therapeutic effects.
About ObsEva:
ObsEva SA is a Swiss clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapeutics for serious conditions that compromise women's reproductive health and pregnancy. Through strategic in-licensing and disciplined drug development, ObsEva has established a late-stage clinical pipeline with development programs focused on treating endometriosis, uterine fibroids and preterm labor. ObsEva is listed on the Nasdaq Global Select Market and is trading under the ticker symbol "OBSV" and on the SIX Swiss Exchange where it is trading under the ticker symbol "OBSN". For more information about ObsEva SA, please visit https://www.obseva.com.
