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

Potency of oral gonadotropin-releasing hormone antagonist as endometriosis-associated pain novel treatments: An updated meta-analysis of randomized controlled trials. (PubMed, Int J Reprod Biomed) - "Bone mineral density in the spine was significantly lower in the treatment group (p 0.001). This meta-analysis provides updated evidence on Elagolix, Linzagolix, and Relugolix, confirming their effectiveness in managing endometriosis-associated pain, while highlighting important considerations regarding metabolic and bone health."

Journal • Retrospective data • Review • Dyslipidemia • Endometriosis • Gynecology • Musculoskeletal Pain • Pain • Women's Health

Cost-Utility Analysis of Linzagolix 200 mg Plus Add-back Therapy (Linzagolix+ABT) for Symptomatic Treatment of Endometriosis (ISPOR-EU 2025) - "Linzagolix was compared against a composite of injectable GnRH agonists (leuprorelin acetate, goserelin, triptorelin). Linzagolix+ABT is cost-effective, enhances HRQoL, and reduces the need for radical surgeries, thereby also helping to preserve fertility. These benefits strongly support the adoption of linzagolix into clinical practice for endometriosis management."

HEOR • Endometriosis • Gynecology • Musculoskeletal Pain • Osteoporosis • Rheumatology • Women's Health

Long-term extension study of Linzagolix for Uterine fibroids: Results after one year of treatment and 6 months post-treatment cessation (ESGE 2025) - "Participants were randomised to receive linzagolix 100 mg, linzagolix 100 mg with hormonal add-back therapy (ABT; 1 mg estradiol / 0.5 mg norethisterone acetate), linzagolix 200 mg, linzagolix 200 mg with ABT, or placebo. Conclusions One-year data from the PRIMROSE trials confirm the sustained efficacy of linzagolix in women with uterine fibroids. The rapid recurrence of symptoms following treatment cessation underscores the potential need for continued long-term therapy in women with uterine fibroids who benefit from oral GnRH antagonists."

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

effectiveness of linzagolix in a clinical setting: preliminary data of an italian real life experience. (ESGE 2025) - "Conclusions Data from this real-world cohort suggest that Linzagolix is effective in significantly reducing menstrual blood loss and improving hemoglobin levels within one month of treatment. Moreover, the use of Linzagolix plays a relevant role as a pre-surgical treatment, allowing optimization of the patients' preoperative profile, reducing uterine fibroid volume, and showing no intraoperative or postoperative complications."

Clinical • Anemia • Cardiovascular • Gynecology • Hematological Disorders • Solid Tumor • Uterine Leiomyoma • Women's Health

Free communication: Outcomes of linzagolix in women with concurrent Endometriosis and Adenomyosis: A post-hoc analysis of the EDELWEISS 3 and 6 trials (ESGE 2025) - "Subjects were randomized to linzagolix 200 mg with hormonal add-back therapy (ABT; 1 mg estradiol/0.5 mg norethisterone acetate), linzagolix 75 mg, or placebo for six months. Conclusions Linzagolix 200 mg+ABT, but not 75 mg, significantly improved DYS in women with concurrent endometriosis and adenomyosis. These findings support the potential benefit of higher-dose linzagolix for this patient population and warrant further investigation."

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

Free communication: Linzagolix rapidly improves heavy menstrual bleeding and anaemia in women with uterine fibroids: A post-hoc analysis of the PRIMROSE 1 and 2 trials (ESGE 2025) - "Eligible women were randomised equally into five arms: linzagolix 100 mg or 200 mg, with or without add-back therapy (ABT; 1 mg oestradiol / 0.5 mg norethisterone acetate), or placebo. In anaemic women, linzagolix also led to greater and faster improvements in Hb and iron biomarkers than placebo. These findings support linzagolix as a novel medical treatment approach for symptomatic uterine fibroids, where a rapid and sustained control of HMB and concurrent improvement in anaemia is required."

Clinical • Retrospective data • Anemia • Gynecology • Hematological Disorders • Solid Tumor • Uterine Leiomyoma • Women's Health

Sequential and Personalized Linzagolix Therapy for Uterine Fibroids: A Rational Clinical Approach. (PubMed, Womens Health Rep (New Rochelle)) - No abstract available

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

Efficacy and Safety of Linzagolix in Black women with uterine fibroids: A post-hoc analysis of the PRIMROSE 1 and PRIMROSE 2 phase 3 trials (ESGE 2025) - "A total of 1,012 participants were randomized equally across five treatment arms: LGX 100 mg, LGX 100 mg with hormonal add-back therapy (ABT; 1 mg estradiol / 0.5 mg norethisterone acetate), LGX 200 mg, LGX 200 mg with ABT, and placebo. Mean bone mineral density (BMD) changes from baseline to Week 24 were: -1.73% (100 mg), -0.45% (100 mg + ABT), -3.68% (200 mg), and -0.33% (200 mg + ABT), indicating a protective effect of ABT on BMD loss. Conclusions LGX had a rapid and sustained effect on reducing clinically significant HMB (all doses) and FV (200mg LGX without ABT) in Black women vs placebo, demonstrating its effectiveness as a potential treatment option even for this higher-risk subset of UF patients."

Clinical • P3 data • Retrospective data • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

Women in Scotland suffering from endometriosis now have access to a new treatment option following the Scottish Medicines Consortium’s (SMC) acceptance of linzagolix with add-back therapy (ABT). (PharmaTimes) - "The once-daily pill is approved for adult women of reproductive age who have previously undergone medical or surgical treatment for the condition."

Reimbursement • Endometriosis

LINZAGOLIX APLICADO A LA PRACTICA CLÍNICA EN PACIENTES CON ÚTEROS MIOMATOSOS (FIGO 2025) - P3 | "Linzagolix logra una significativa reducción del sangrado menstrual y el volumen de los miomas, mejorando la calidad de vida de las pacientes. Name of public trials registry in which the study has prospective registration: Registro Español de ensayos clinicos con identificador: 2019-000283-26 URL of registration: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01475-1/abstract Full study dates (day, month, and year): 1 de octubre 2024 hasta 1 de octubre 2025. Inclusion/exclusion criteria: Criterios de inclusion: pacientes en edad reproductiva con sangrado menstrual abundante y útero miomatoso."

Osteoporosis • Rheumatology

Linzagolix - new perspectives in the pharmacotherapeutic management of uterine fibroids and endometriosis. (PubMed, Prz Menopauzalny) - "Linzagolix, with or without add-back therapy, significantly alleviates the symptoms of both uterine fibroids and endometriosis in a dose-dependent manner - the therapeutic effect is rapid and sustained. This drug constitutes a valuable addition to existing methods for treating oestrogen-dependent diseases because it enables treatment personalisation allowing for dose adjustment and the optional use of add-back therapy."

Journal • Review • Endometriosis • Gynecology • Hematological Disorders • Infertility • Musculoskeletal Pain • Pain • Sexual Disorders • Solid Tumor • Uterine Leiomyoma • Women's Health

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