Yselty (linzagolix) / Kissei, Theramex, Syneos Health, Synmosa Biopharma, Bio Genuine, JW Pharma - LARVOL DELTA

Oral Gonadotropin-Releasing Hormone Antagonists in the Treatment of Endometriosis: Advances in Research. (PubMed, J Clin Med Res) - "The primary objective of this review is to comprehensively evaluate the clinical efficacy and safety profile of oral GnRH antagonists, specifically elagolix, relugolix, linzagolix, and opigolix, for the management of endometriosis-associated pain. Furthermore, when combined with add-back therapy, these medications enhance treatment safety and contribute to greater patient compliance. Compared to alternative hormonal treatments, oral GnRH antagonists emerge as a particularly promising approach for managing endometriosis."

Journal • Review • Endometriosis • Gynecology • Musculoskeletal Pain • Pain • Women's Health

Two-year follow-up study (PRIMROSE 3) to assess bone mineral density in subjects with uterine fibroids completing the PRIMROSE 1 and PRIMROSE 2 linzagolix trials. (PubMed, Hum Reprod Open) - P3 | "It can be assumed that the small BMD changes observed from both the post-treatment and pre-treatment baseline to month 24 after cessation of therapy may not have any clinically relevant impact on overall bone health of linzagolix-treated individuals.Changes in BMD values and Z-scores in the linzagolix treatment groups were mostly within the same range as in the placebo group, indicating that there are no long-term consequences on BMD after the end of linzagolix treatment."

Journal • Endometriosis • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

Linzagolix with and without hormonal add-back therapy for symptomatic uterine fibroids: PRIMROSE 1 & 2 long-term extension and withdrawal study. (PubMed, Fertil Steril) - "Findings at 52 weeks confirmed the benefits of treatment observed at 24 weeks. At 52 weeks, linzagolix (100 mg or 200 mg) with or without ABT was found to reduce heavy menstrual bleeding, which is a burden for women with uterine fibroids. Their quality of life was improved. Risks of bone loss and vasomotor symptoms were minimized as a result of ABT administration. Partial suppression with once daily linzagolix (100 mg) without ABT potentially provides a unique option for chronic treatment of symptomatic uterine fibroids in women who do not wish to have ABT or in whom it is contraindicated. The relatively fast recurrence of uterine fibroid-associated symptoms after cessation of therapy is an argument in favour of long-term continuation of treatment."

Journal • Gynecology • Osteoporosis • Pain • Solid Tumor • Uterine Leiomyoma • Women's Health

Efficacy and safety of drug combinations for chronic pelvic pain: a systematic review. (PubMed, Pain Rep) - "Nine studies (1,299 participants) were included and involved various different treatments including ciprofloxacin, tamsulosin, pentosan polysulfate, hyaluronic acid, chondroitin, hydroxyzine, troxerutin, carbazochrome, linzagolix, and allopurinol. None of the included studies reported a significant difference in reducing pain intensity for combination therapy vs monotherapy. If future proof-of-concept studies demonstrate that a given combination is superior to all monotherapy components, subsequent large, double-blind randomized, controlled clinical trials of such combinations for CPP are required to better elucidate the role of combination therapy in clinical settings."

Clinical • Journal • Review • Gynecology • Musculoskeletal Pain • Pain

A Clinical Study of KLH-2109 in Patients With Endometriosis (clinicaltrials.gov) - P3 | N=288 | Recruiting | Sponsor: Kissei Pharmaceutical Co., Ltd.

New P3 trial • Endometriosis • Gynecology • Women's Health

Long-Term Extension Study to Assess the Effect of Linzagolix in Women with Endometriosis-Associated Pain (EDELWEISS-6 trial) (WCE 2025) - "Materials and Methods Following completion of the principal EDELWEISS-3 trial, participants were invited to continue treatment for a further six months with either linzagolix 75mg or 200mg plus hormonal add-back therapy (1mg estradiol/0.5mg norethindrone acetate) for their EAP. Similarly, efficacy on key secondary endpoints demonstrated at month 6 continued to improve up to month-12. Overall, linzagolix was well- tolerated over the 12-months treatment course in EDELWEISS-3 and -6 trials."

Clinical • Endometriosis • Gynecology • Musculoskeletal Pain • Pain • Women's Health

Linzagolix Outcomes in Women with Concurrent Endometriosis and Adenomyosis: A Post-Hoc Analysis of the EDELWEISS-3 and 6 Trials (WCE 2025) - "Patients were randomised to receive linzagolix 75mg, 200mg plus add-back therapy (1mg estradiol/0.5mg norethindrone acetate), or placebo for 6-months. Conclusion Linzagolix 200mg+ABT significantly improved DYS in patients with concurrent endometriosis and adenomyosis, indicating this higher dose may be optimal for this subgroup. Further investigation is warranted."

Clinical • Retrospective data • Endometriosis • Gynecology • Inflammation • Musculoskeletal Pain • Pain • Women's Health

Pain Reduction in Linzagolix-Treated Patients With Uterine Fibroids: A Secondary Mediation Analysis of the PRIMROSE 1 and 2 Phase 3 Trials. (PubMed, BJOG) - P3 | "This analysis showed that reductions in pain were significantly mediated by reductions in HMB (all doses) and FV (200 mg alone) in linzagolix-treated women with UFs. Further research is needed to identify additional mediating factors."

Journal • P3 data • Gynecology • Pain • Solid Tumor • Uterine Leiomyoma • Women's Health

NHS approves 'game-changing' at-home pill for endometriosis (Mirror) - "A groundbreaking at-home pill for endometriosis, known as linzagolix or Yselty, has been given the green light for use on the NHS. The daily tablet could potentially benefit up to 1,000 women a year who are battling with the condition."

NICE • Endometriosis • Women's Health

A Clinical Study of KLH-2109 in Uterine Fibroids Patient With Menorrhagia (clinicaltrials.gov) - P3 | N=287 | Completed | Sponsor: Kissei Pharmaceutical Co., Ltd. | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Aug 2024 | Trial primary completion date: May 2025 ➔ Aug 2024

Trial completion • Trial completion date • Trial primary completion date • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

A Clinical Study of KLH-2109 in Uterine Fibroids Patient With Menorrhagia and Pain (clinicaltrials.gov) - P3 | N=89 | Completed | Sponsor: Kissei Pharmaceutical Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Gynecology • Pain • Solid Tumor • Uterine Leiomyoma • Women's Health

Efficacy of GnRH antagonists in the treatment of uterine fibroids: a meta-analysis. (PubMed, Arch Gynecol Obstet) - "GnRH antagonists represent an effective alternative for uterine fibroids treatment as they allow a superior reduction in menstrual bleeding and uterine fibroid volume compared to the placebo group."

Clinical • Journal • Retrospective data • Review • Gynecology • Oncology • Solid Tumor • Uterine Leiomyoma • Women's Health

Theramex Announces European Commission Approval for Yselty (linzagolix) for Symptomatic Treatment of Endometriosis in Women with a History of Previous Medical or Surgical Treatment for their Endometriosis (Theramex Press Release) - "Theramex...is pleased to announce that the European Commission (EC) has approved an extended indication for Yselty (linzagolix), an oral gonadotropin-releasing hormone (GnRH) antagonist, for the symptomatic treatment of endometriosis in adult women of reproductive age with a history of previous medical or surgical treatment for their endometriosis. This approval, effective immediately, applies to EU markets (excluding the UK and non-EU markets)...The EC approval follows the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) positive opinion in October 2024, based on results from the EDELWEISS 3 study."

EMA approval • Endometriosis

Aifa approves reimbursement of Linzagolix Colina, innovative therapy for the treatment of uterine fibroids [Google translation] (Social Farma) - "The Italian Medicines Agency has granted reimbursement to the drug linzagolix choline for the treatment of uterine fibroids. It is a GnRH (gonadotropin-releasing hormone) receptor antagonist, indicated for the treatment of moderate and severe symptoms of uterine fibroids in adult women of reproductive age, over the age of 18."

Reimbursement • Uterine Leiomyoma

The use of oral GnRH antagonist to inhibit the LH surge in women undergoing ovarian stimulation for in vitro fertilization. (PubMed, Expert Rev Clin Pharmacol) - No abstract available

Journal • Preclinical • Gynecology

SMC recommends Yselty for treating uterine fibroids (PharmaTimes) - "The Scottish Medicines Consortium (SMC) has recommended Yselty (linzagolix) for treating moderate to severe symptoms of uterine fibroids (UFs) in women of reproductive age. This decision means eligible women across Scotland can now access this treatment through the NHS...The approval is based on data from two PRIMROSE studies that investigated the efficacy and safety of Yselty in women with uterine fibroids and heavy menstrual bleeding."

Reimbursement • Oncology • Uterine Leiomyoma • Women's Health

Cost-Effectiveness of Linzagolix for Uterine Fibroids in Australia: A Healthcare Payer and Societal Perspective (ISPOR-EU 2024) - "There is an urgent clinical need for reimbursed treatments for moderate to severe symptoms of UFs, which include HMB and can severely impact women’s quality of life (QoL), mental health, and daily activities. This analysis indicates that linzagolix provides a meaningful QoL improvement at a reliably estimated and reasonable level of cost-effectiveness – even more so when a societal perspective is considered."

Cost effectiveness • HEOR • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

Edelweiss-6: long-term effects of linzagolix in women with endometriosis-associated pain (ESGE 2024) - "This extension study assessed the long-term effects of linzagolix in women with moderate to severe EAP.Methods After the 6-month treatment period in the principal Edelweiss-3 study, women could choose to continue treatment for a further 6 month with either linzagolix 75mg alone or linzagolix 200mg plus add-back therapy (ABT; 1mg estradiol/0.5mg norethindrone acetate). Overall, Linzagolix was well-tolerated over the course of the 12 months treatment.Conclusions Improvements observed at Month 6 in DYS and NMPP were generally increased at month 12 in both linzagolix 75 mg and 200 mg+ABT groups. Similarly, the observed efficacy on secondary endpoints showed a trend for improvement at month 12."

Clinical • Endometriosis • Gynecology • Musculoskeletal Pain • Pain • Women's Health

Edelweiss 3: efficacy results from a multinational, randomized, placebo-controlled phase 3 study testing two doses of linzagolix in women with endometriosis associated pain. (ESGE 2024) - "Women were equally randomized and treated with linzagolix 75mg, 200mg plus add-back therapy (ABT; 1mg estradiol/0.5mg norethindrone acetate) or placebo for 6 months. Both doses offered a statistically significant improvement in the interference of pain with daily activities as measured on the EHP-30 pain dimension, with a mean change from baseline of ‑35.60 (95%CI: ‑38.73, ‑32.48; p<0.001) and -27.37 (95%CI: ‑30.50, ‑24.25; p=0.001) for the 200mg+ABT and 75mg group, respectively.Conclusions Linzagolix 200mg+ABT treatment significantly improved both DYS and NMPP at month 3 and 6, with statistically significant improvements also seen for dyschezia, overall pelvic pain and interference of pain with daily activities. 75mg dose on the other hand improved DYS symptoms alone at month 3, whilst statistically significant improvements in NMPP and other secondary endpoints were seen by month 6."

Clinical • P3 data • Endometriosis • Gynecology • Musculoskeletal Pain • Pain • Women's Health

Iselty (generic name: Linzagolix), a treatment for uterine fibroids, is now available in Europe [Google translation] (Kissei Press Release) - "Kissei Pharmaceutical Co., Ltd...is pleased to announce that Theramex Limited (UK), a licensee of Kissei's technology, has launched Linzagolix (generic name, domestic development code: KLH-2109), a treatment for uterine fibroids, in Germany for the first time in the world under the product name 'YSELTY'."

Launch non-US • Uterine Leiomyoma • Women's Health

NICE recommends Yselty (linzagolix) for treating moderate to severe symptoms of uterine fibroids in adult women of reproductive age (PharmiWeb) - "Theramex has announced that the National Institute for Health and Care Excellence (NICE) has recommended Yselty for the treatment of moderate to severe symptoms of uterine fibroids (UFs), aligned to the product indication in adult women of reproductive age...This decision by NICE means that Yselty will be available for eligible women across England and Wales through the NHS. The NICE decision is based on evidence from the two PRIMROSE studies (of replicate design) investigating the efficacy and safety of Yselty in women who have uterine fibroids with heavy menstrual bleeding (HMB)."

NICE • Gynecology • Oncology • Solid Tumor • Uterine Leiomyoma • Women's Health

JW Pharm acquires rights for Kissei Pharmaceutical’s uterine fibroid treatment (Korea Biomedical Review) - "JW Pharmaceutical said it has entered into a licensing agreement with Japan's Kissei Pharmaceutical for the introduction of the latter's Linzagolix, a treatment for uterine fibroids, in Korea. Under the accord, JW Pharmaceutical will hold exclusive rights to develop, commercialize, use, develop, sell, offer for sale, import, and manufacture Linzagolix in Korea....JW Pharmaceutical anticipates that the introduction of Linzagolix will significantly benefit domestic patients as its oral administration offers convenience, which will likely lead to enhancing the quality of life for uterine fibroid patients in Korea."

Licensing / partnership • Uterine Leiomyoma • Women's Health

Linzagolix therapy versus a placebo in patients with endometriosis-associated pain: a prospective, randomized, double-blind, Phase 3 study (EDELWEISS 3). (PubMed, Hum Reprod) - P3 | "Linzagolix administered orally once daily at a dose of 200 mg in combination with add-back therapy (ABT) demonstrated better efficacy and safety than placebo in the management of moderate-to-severe endometriosis-associated pain. The quality of life was improved and the risks of bone loss and vasomotor symptoms were minimized due to the ABT. The 75 mg dose alone could be suitable for chronic treatment of endometriosis-associated pain without the need for concomitant hormonal ABT, but further research is needed to confirm this. If confirmed, it would offer a viable option for women who do not want to wish to have ABT or for whom it is contraindicated."

Clinical • Journal • P3 data • Endometriosis • Gynecology • Musculoskeletal Pain • Osteoporosis • Pain • Women's Health

EDELWEISS 3 trial: Linzagolix effectively reduces endometriosis-associated pain in a placebo-controlled Phase III study. (ISGE 2024) - "This randomized, double-blind, placebo-controlled trial assessed the efficacy and safety of daily doses of LGX at 75mg alone and 200mg with hormonal add-back therapy (ABT; 1mg estradiol/0.5mg norethindrone acetate), over a 6-month period, In women with moderate to severe EAP. The study demonstrates the efficacy of both 200 mg LGX with ABT and 75 mg LGX in reducing endometriosis-associated pain. The 200 mg dose with ABT demonstrated significant improvements at 3 and 6 months in DYS and NMPP. Overall, both Linzagolix doses were well tolerated, and BMD changes were minimal following 6 months of treatment."

Clinical • P3 data • Endometriosis • Gynecology • Musculoskeletal Pain • Pain • Solid Tumor • Uterine Leiomyoma • Women's Health

ADVANCEMENTS IN UTERINE FIBROIDS: LINZAGOLIX OFFERS A POSSIBILITY TO INDIVIDUALISE THERAPY (ISGE 2024) - "Sponsored By THERAMEX"

Clinical • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health