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December 10, 2020

The Efficacy and Safety Results of the Overseas Phase-III Long-Term Study of Uterine Fibroids for GnRH Antagonist, Linzagolix, conducted by ObsEva

Kissei Pharmaceutical Co., Ltd. (Head Office: Matsumoto, Nagano; Chairman and CEO: Mutsuo Kanzawa) is pleased to announce that the GnRH antagonist "Linzagolix (KLH-2109/OBE2109)" that was discovered by Kissei and licensed out to ObsEva SA (Main Office: Geneva, Switzerland; CEO: Mr. Brian O'Callaghan) had the results of the 2 phase 3 studies for uterine fibroids (PRIMROSE 1 and 2) announced by ObsEva on December 10, 2020 CET.

The PRIMROSE studies is a Phase 3 clinical trial to observe the efficacy and safety of the use of linzagolix 100mg, 100mg with Add-back therapy (ABT), 200mg or 200mg with ABT once daily on patients with uterine fibroids. The released results are of the PRIMROSE 1, 52-week long-term study and PRIMROSE 2, 76-week study (post-administration observational period at 24 weeks).

The primary end point of the PRIMROSE studies was the responder rate of subjects whose menstrual bloodloss was less than 80mL and reduced by more than 50% from baseline. Similar results as PRIMROSE 2 which has already been released was observed in this study. The pooled data of the 2 phase 3 study resultsshowed responder rate of 56.4% in the 100mg alone and 89.3% in the 200mg with ABT. In the arm where linzagolix 200mg alone was administered for 24 weeks, then added combination use of ABT, the volume of the uterine and fibroid decreased substantially during the linzagolix single use period. These results supports the high dose regimen of linzagolix without ABT to be an option for patients who are in need of rapid shrinkage of the uterine and fibroid volume.
In the PRIMROSE 2 study, the pain score was sustained at a low score in the linzagolix treatment group even 3 months after the end of treatment in comparison to before the administration.

Safety results from week 24 to 52 of PRIMROSE 1 study showed low occurrence of hotflushes, headaches and anemia which were the most frequently observed adverse events up to week 24 (incidence rate > 5%). For subjects who continued treatment beyond 24 weeks, safety results showed similar incidence rate of adverse events between placebo and active treatment. With regards to BMD, the incremental decrease in lumbar spine was similar to placebo in the 100mg treatment arm at week 52 compared to week 24, with less change seen in the 200mg with ABT. In the PRIMROSE 2 study at week 76 (week 24 of the post-administration observational period), both 100mg alone and 200mg with ABT treatment arm showed recovery in BMD.
In the PRIMROSE studies, supplements such as vitamin D and calciums has not been coincomitantly used.

From the results observed, ObsEva considers linzagolix to become the only GnRH antagonist with a flexible dose option of 100mg, 200mg and 200mg + ABT. Linzagolix has already been submitted for MAA to the European Medicines Agency (EMA) in November 2020, and will be submitting for NDA to the U.S. Food and Drug Administration (FDA) in 1H 2021.


For more details of the released results, please refer to ObsEva's website.

These clinical results have neglible 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 574 women, whilst PRIMROSE 2 has been conducted in Europe and in the United States 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. ObsEva released the 24-week interim results of PRIMROSE 2 trial in December 2019 and the 24-week interim results of PRIMROSE 1 trial in July 2020, as well as the results of a long-term administration trial at 52-weeks of administration for PRIMROSE 2 trial.

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.

Treatment of Uterine Fibroids in the U.S.:

Uterine fibroids is a benign tumour that forms in the muscle tissue of the uterus and is frequently seen in females of childbearing age. Menorrhagia, anemia, pain, pelvic pressure, frequent urination are some of the symptoms seen and affects the daily life of patients. In the U.S, the long-term medical treatment is scarce and therefore surgery is a common option. There are 300,000 hysterectomy conducted annually as a treatment of uterine fibroid.

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.