Partial suppression of estradiol with moderate dose (75mg) of linzagolix demonstrated highly significant reduction of pain and improvement of patient well-being
High dose (200mg) of linzagolix achieves full estradiol suppression and highly significant efficacy
Excellent safety profile demonstrated
EDELWEISS is a Phase 2b, randomized, double blind, placebo controlled clinical trial designed to evaluate the safety and efficacy of multiple doses of linzagolix in 327 women with moderate-to-severe endometriosis-associated pain recruited from 64 gynecological clinics across the U.S. and
The primary endpoint of the EDELWEISS clinical trial was a responder analysis, with responses defined as a reduction of at least 30% in combined menstrual and non-menstrual pelvic pain, recorded daily and assessed via electronic diary over the last 28 days of treatment on a verbal rating scale (VRS) of 0 (no pain) through 3 (severe pain).
Demographics and baseline characteristics were comparable between groups with a mean baseline overall pain VRS of 1.7, menstrual pain VRS of 2.1 and non-menstrual pain VRS of 1.6.
Primary Endpoint Results:
- The study primary endpoint was achieved for the three top doses, and patients receiving a 75mg dose had the highest responder rate of 61.5% compared to the placebo at 34.5%.
*as per protocol
Secondary Endpoint Results:
- With respect to the menstrual pain VRS, patients receiving a 200mg dose reported the highest responder rate at 78.9%, compared to a placebo responder rate of 28.5%.
- Responder rates for the non-menstrual pain VRS endpoint were statistically significant for the 75mg dose and the 100mg dose and both doses showed comparable responder rates at 58.5% and 61.5% respectively.
*200mg at week 8: responder rate 57.0% (p=0.022)
In addition, doses of linzagolix from 75mg to 200mg significantly and consistently improved dyschezia and patient well-being as assessed by Endometriosis Health Profile-30 score, Patient Global Impression of Change scale (PGIC), Patient Global Impression of Severity (PGIS), the activity impairment score and the modified Biberoglu & Behrman score. Dyspareunia was also improved for all doses and reached statistical significance at the 200mg dose.
Serum Estradiol median levels at week 12 were 12 pg/ml for the 200mg dose and 48 pg/ml for the 75mg dose, which indicates full suppression at the higher dose and partial suppression at the 75mg dose.
Linzagolix was observed to be safe and well tolerated. In line with the therapeutic class and mechanism of action, a moderate proportion of patients reported at least one hot flush as an adverse event (which is a side effect of suppression of E2 levels). The incidence of hot flush in the most effective 75mg dose cohort was 18.4%, versus the placebo arm of 10.9%. Additionally, the incidence of hot flush in the 200mg dose cohort was 42.1%, which is expected for a full E2 suppression dose.
"We are very pleased by the EDELWEISS results reported today. We believe that these data strongly support the therapeutic potential of linzagolix for improving the condition and well-being of patients suffering from endometriosis. In addition, we believe these data further confirm
Currently, patients in the EDELWEISS trial continue to receive linzagolix for an additional 12 weeks. Twenty-four-week data, including the bone mineral density (BMD) assessment, is expected to be available in the fourth quarter of 2018.
Conference Call Information
Endometriosis is associated with a multitude of symptoms, most common is severe pain during menstruation as well as chronic pelvic pain throughout the menstrual cycle or during intercourse. In addition, endometriosis is a leading cause of infertility.
Endometriosis is a disease in which the endometrium (tissue lining the inside of the uterus) is found outside the uterus, where it induces a chronic inflammatory reaction that may result in scar tissue. It is primarily found on the pelvic endometrium, on the ovaries, in the rectovaginal septum, on the bladder and bowel. The most common symptom of endometriosis is pelvic pain, which often correlates to the menstrual cycle. Patients may also experience painful ovulation, pain during or after sexual intercourse, dyschezia (difficult or painful defecation), heavy bleeding, chronic pelvic pain, fatigue and infertility. Endometriosis pain can be so severe and debilitating that it affects day-to-day activities and has a negative impact on general, physical, mental and social well-being. Endometriosis treatments aim first to alleviate pain, then to remove or decrease the size and number of endometrial lesions, and possibly improve fertility. Oral contraceptives, progestins and NSAIDs are generally first-line treatments for women experiencing pain. Following the failure of first-line therapies, current treatment options are limited to intra-muscular or subcutaneous GnRH agonist injections, GnRH agonists nasal spray pumps or surgery (including hysterectomy) for the most symptomatic cases.
About LINZAGOLIX (OBE2109)
Linzagolix is a novel, orally administered GnRH receptor antagonist with a potentially best-in-class profile in late stage clinical development for the treatment of pain associated with endometriosis and heavy menstrual bleeding associated with uterine fibroids. Linzagolix acts by binding to and blocking the GnRH receptor in the pituitary gland, ultimately reducing estrogen production by the ovaries. Given reported results from this class of drugs and sophisticated pharmacological modelling, linzagolix is being developed to potentially provide two regimens of administration, one targeting partial suppression of estradiol that may not necessitate add-back therapy (ABT) in the majority of patients, and one targeting full or near full estradiol suppression that would require the administration of ABT, with the goal of providing appropriate treatment to the broadest possible proportion of the endometriosis and uterine fibroid patient populations. ObsEva licensed OBE2109 from Kissei in 2015 and retains worldwide rights, excluding
To date, more than 1500 subjects have been exposed to linzagolix.
Kissei is a Japanese pharmaceutical company with approximately 70 years of history, specialized in the field of urology, kidney-dialysis and unmet medical needs. Silodosin is a Kissei product for the treatment of the signs and symptoms of benign prostatic hyperplasia which is sold worldwide through its licensees. KLH-2109/OBE2109/linzagolix is a new chemical entity discovered by Kissei R&D.
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