Myfembree (relugolix/estradiol/norethindrone acetate) / Sumitomo Pharma, Pfizer, ASKA Pharma, Knight Therap - LARVOL DELTA

Post-marketing safety profile of Myfembree in approved gynecologic indications: a disproportionality analysis based on the FAERS database. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Myfembree, a fixed-dose combination of relugolix, estradiol, and norethindrone acetate, is approved for premenopausal women with heavy menstrual bleeding associated with uterine fibroids and moderate to severe pain associated with endometriosis. These findings were generally consistent with the known safety profile of the drug and provide additional evidence on adverse event patterns and onset timing in routine gynecologic practice. Continued pharmacovigilance is warranted, particularly for thromboembolic events, blood pressure-related events, mood-related symptoms, and treatment-associated bleeding abnormalities."

Journal • P4 data • Alopecia • Cardiovascular • CNS Disorders • Depression • Endometriosis • Gynecology • Hematological Disorders • Immunology • Pain • Psychiatry • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • Suicidal Ideation • Uterine Leiomyoma • Women's Health

Achieving Minimal-to-No Pain in Women with Endometriosis Treated with Relugolix Combination Therapy: SPIRIT Extension Trial. (PubMed, Int J Womens Health) - "Relugolix is an oral, non-peptide gonadotropin-releasing hormone receptor antagonist administered as once-daily combination therapy (relugolix-CT; 40 mg relugolix, 1 mg estradiol, 0.5 mg norethindrone acetate) to reduce endometriosis symptoms while potentially minimizing hypoestrogenic effects. Analgesic-free status improved in the placebo group after relugolix-CT initiation. In this post hoc analysis, women receiving relugolix-CT for up to 104 weeks had rapid dysmenorrhea improvement with amenorrhea and reduced analgesic use, with longer treatment associated with further NMPP reduction."

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

Once-daily oral Gonadotropin-Releasing Hormone (GnRH) antagonists in the treatment of uterine fibroids: from evidence to clinical practice. (PubMed, Eur J Obstet Gynecol Reprod Biol) - "Among these agents, two once-daily oral GnRHa are approved for uterine fibroids: relugolix combination therapy (CT) (Ryeqo in the EU, Myfembree in the US), taken as a single tablet daily with add-back incorporated (relugolix 40 mg + estradiol 1 mg + norethindrone acetate 0.5 mg); and linzagolix, administered as 100 mg daily (partial suppression) or 200 mg daily (full suppression) (Yselty in the EU/UK), without or with add-back (an additional tablet with 1 mg estradiol + 0.5 mg norethindrone acetate). Linzagolix 200 mg is a suitable option for short-term preoperative fibroid reduction. Their distinct pharmacological profiles and dosing strategies may support different therapeutic objectives, including long-term symptom control and short-term preoperative management."

Journal • Review • Gynecology • Hematological Disorders • Solid Tumor • Uterine Leiomyoma • Women's Health

Comparative post-marketing reporting signals of elagolix and myfembree in endometriosis: a FAERS pharmacovigilance study. (PubMed, Front Pharmacol) - "These findings represent hypothesis-generating reporting differences rather than clinical incidence rates or causal risk estimates. Further pharmacoepidemiologic studies with denominator data and adjustment for patient-level confounding are needed to clarify comparative safety profiles."

Adverse events • Journal • P4 data • Alopecia • CNS Disorders • Depression • Endometriosis • Gynecology • Immunology • Musculoskeletal Pain • Pain • Psychiatry • Suicidal Ideation • Women's Health

Bioequivalence of a Fixed-Dose Combination of Relugolix, Estradiol, and Norethindrone Acetate: An Open-Label, Randomized, Fully Replicate Crossover Study in Healthy Postmenopausal Women Under Fasting Conditions. (PubMed, Clin Pharmacol Drug Dev) - "The relugolix/estradiol/norethindrone acetate FDC demonstrated bioequivalence to the globally approved reference product (MYFEMBREE) with comparable tolerability. This provides a safe, effective, reversible non-surgical therapy for fibroid-related HMB, fulfilling an unmet need beyond surgery."

Clinical • Journal • Gynecologic Cancers • Gynecology • Hematological Disorders • Oncology • Solid Tumor • Uterine Leiomyoma • Women's Health

The Effect of Medical Management Following Excisional Surgery for Endometriosis: A Randomized Controlled Trial (clinicaltrials.gov) - P3 | N=110 | Recruiting | Sponsor: Main Line Health | Trial completion date: Aug 2026 ➔ Dec 2028 | Trial primary completion date: Feb 2026 ➔ Jun 2028

Trial completion date • Trial primary completion date • Endometriosis • Gynecology • Women's Health

SERENE: Study of the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are at Risk for Pregnancy (clinicaltrials.gov) - P3 | N=1164 | Completed | Sponsor: Sumitomo Pharma Switzerland GmbH | Active, not recruiting ➔ Completed

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

The Impact of a Novel GnRH Antagonist With Add-back Therapy for Treatment of Uterine Fibroids and Endometriosis on Hemostasis Parameters (clinicaltrials.gov) - P=N/A | N=30 | Recruiting | Sponsor: University Hospital, Geneva | Trial completion date: Dec 2026 ➔ Mar 2027

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

Oral Gonadotropin-Releasing Hormone Antagonists for the Treatment of Endometriosis-Associated Pain: A Systematic Review and Meta-Analysis. (PubMed, J Minim Invasive Gynecol) - "Oral GnRH antagonists provide consistent, significant, and clinically meaningful reductions in dysmenorrhea and non-menstrual pelvic pain compared with placebo, with low heterogeneity across trials and similar efficacy among elagolix, relugolix combination therapy, and linzagolix with add-back, supporting their use as effective second-line therapy for endometriosis-associated pain."

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

Improvement of vasomotor symptoms of perimenopausal women with symptomatic fibroids treated with relugolix 40 mg combination therapy (ISGE 2026) - "Objective: To evaluate the effects of relugolix 40 mg + continuous combined hormone therapy preparation containing 1mg estradiol (E2) and 0.5 mg norethisterone acetate on the number and intensity of moderate and severe hot flushes in women in perimenopause treated for symptomatic uterine fibroids. Treatment of fibroids with relugolix CT induced a significant reduction of moderate and severe hot flushes in perimenopausal symptomatic women. This initial clinical observation could revolutionize the way we can treat climacteric symptoms during perimenopausal period in the near future in women with fibroids but maybe in the general population."

Clinical • Combination therapy • Alopecia • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

GnRH Antagonist with Add-Back in Uterine Fibroids: Real-World Experience with Ryeqo® (ISGE 2026) - "Context: Real-world evidence on relugolix/estradiol/norethindrone acetate (Ryeqo®) for fibroid-related heavy menstrual bleeding is expanding, but pragmatic series with routine-care follow-up remain limited. In real-world practice, Ryeqo® showed high bleeding control (approximately 80%) with good persistence (approximately 3 in 4 ongoing). No firm conclusions on age can be drawn due to group imbalance and the small <40 sample, but these data support further study with standardized volumetric measures. Discontinuations were mostly due to expected situations."

Clinical • Real-world • Real-world evidence • CNS Disorders • Endometriosis • Gynecology • Migraine • Solid Tumor • Uterine Leiomyoma • Women's Health

Surgical Myomectomy Followed by Oral Myfembree Versus Standard of Care Trial (SOUL) (clinicaltrials.gov) - P4 | N=0 | Withdrawn | Sponsor: University of Chicago | N=136 ➔ 0 | Terminated ➔ Withdrawn

Enrollment change • Trial withdrawal • Endometrial Cancer • Gynecology • Musculoskeletal Pain • Pain • Solid Tumor • Uterine Leiomyoma

Estradiol-mediated Inflammation and Central Sensitization in the Pathophysiology of Endometriosis-associated Pelvic Pain (clinicaltrials.gov) - P3 | N=130 | Recruiting | Sponsor: University of Michigan | Initiation date: Aug 2025 ➔ Nov 2025

Trial initiation date • Endometriosis • Gynecology • Inflammation • Musculoskeletal Pain • Pain • Women's Health • CCL3

The Impact of a Novel GnRH Antagonist With Add-back Therapy for Treatment of Uterine Fibroids and Endometriosis on Hemostasis Parameters (clinicaltrials.gov) - P=N/A | N=30 | Recruiting | Sponsor: University Hospital, Geneva

New trial • Endometriosis • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

Phenotyping of Idiopathic Pelvic Pain With Real-time Uterine Imaging and Relugolix-Combination Therapy Treatment (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Endeavor Health | N=60 ➔ 0 | Trial completion date: Aug 2025 ➔ Nov 2025 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Aug 2025 ➔ Nov 2025

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Gynecology • Musculoskeletal Pain • Pain

MYFEMBREE®: A Retrospective Cohort Study Using an Administrative Healthcare Database to Assess Pregnancy Outcomes in Women Treated With Relugolix Combination Therapy (clinicaltrials.gov) - P=N/A | N=530 | Active, not recruiting | Sponsor: Sumitomo Pharma Switzerland GmbH | Not yet recruiting ➔ Active, not recruiting

Enrollment closed

Estradiol-mediated Inflammation and Central Sensitization in the Pathophysiology of Endometriosis-associated Pelvic Pain (clinicaltrials.gov) - P3 | N=130 | Recruiting | Sponsor: University of Michigan | Not yet recruiting ➔ Recruiting

Enrollment open • Endometriosis • Gynecology • Inflammation • Musculoskeletal Pain • Pain • Women's Health • CCL3

Estradiol-mediated Inflammation and Central Sensitization in the Pathophysiology of Endometriosis-associated Pelvic Pain (clinicaltrials.gov) - P3 | N=130 | Not yet recruiting | Sponsor: University of Michigan

New P3 trial • Endometriosis • Gynecology • Inflammation • Musculoskeletal Pain • Pain • Women's Health • CCL3

Surgical Myomectomy Followed by Oral Myfembree Versus Standard of Care Trial (SOUL) (clinicaltrials.gov) - P4 | N=136 | Terminated | Sponsor: University of Chicago | Trial completion date: Apr 2026 ➔ Oct 2024 | Recruiting ➔ Terminated | Trial primary completion date: Oct 2025 ➔ Oct 2024; The study team has discovered that for some subjects, the consent process, study drug storage, and eligibility screening were not administered in ways that are consistent with the study protocol approved by the Institutional Review Board.

Trial completion date • Trial primary completion date • Trial termination • Endometrial Cancer • Gynecology • Musculoskeletal Pain • Pain • Solid Tumor • Uterine Leiomyoma

Knight Therapeutics and Sumitomo Pharma enter into Exclusive Licensing Agreements to commercialize Sumitomo’s Canadian Portfolio (GlobeNewswire) - "Knight Therapeutics Inc...and Sumitomo Pharma America Inc. ('SMPA') announced today that Knight and SMPA’s affiliates have entered into exclusive license and supply agreements to commercialize MYFEMBREE (relugolix/estradiol/norethindrone acetate), ORGOVYX (relugolix)...in Canada, as well as an asset purchase agreement under which Knight will acquire certain mature products (the 'Mature Products', together with MYFEMBREE, ORGOVYX and vibegron, the 'Products'). For the year ended March 2025, the Products generated C$11.2 million in revenue. Under the terms of the agreements, Knight will have the exclusive rights to distribute, promote, market and sell the Products in Canada. Knight will begin commercial activities following a transition period from Sumitomo Pharma Canada."

Commercial • Prostate Cancer • Uterine Leiomyoma • Women's Health

Beyond the Pelvis - A Case of Thoracic Endometriosis Syndrome (ATS 2025) - "She also underwent diagnostic laparoscopy with lysis of adhesions with findings of severe adnexal disease s/p cauterization and was started on Relugolix, estradiol and norethindrone with successful hormonal suppression of menses...She was offered Lupron, however, deferred it due to risk of medical menopause...Surgery including VATs or open thoracotomy with lysis of adhesions and chemical or pleurodesis remain important management options. In patients presenting with TES, we recommend multidisciplinary approach with specialists in pulmonary medicine, cardiothoracic surgery and obstetrics and gynecology."

Clinical • Cardiovascular • Endometriosis • Gynecology • Hypertension • Obstetrics • Rare Diseases • Respiratory Diseases • Women's Health

Ultrasound Transformation of Myomas During Relugolix-Estradiol-Norethisterone Treatment: The MySaturn Study (clinicaltrials.gov) - P=N/A | N=111 | Not yet recruiting | Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

New trial • Hematological Disorders • Oncology • Solid Tumor • Uterine Cancer • Uterine Leiomyoma

Inhibition of ovulation and pharmacologic mechanism of action of relugolix combination therapy. (PubMed, Fertil Steril) - "Relugolix combination therapy inhibits ovulation, which, in the context of this study, was achieved within the first cycle following treatment initiation. The rapid and predictable return of ovarian activity and ovulation following treatment discontinuation is advantageous for patients who wish to conceive thereafter."

Journal

Transfer of the Oral Gonadotropin-Releasing Hormone Receptor Antagonist Relugolix Into Breast Milk of Healthy Lactating Women. (PubMed, Pharmacol Res Perspect) - "The body weight-adjusted relative daily infant dose of approximately 0.25% suggests a 400-fold lower newborn than maternal relugolix exposure. Relevant effects of relugolix on the breastfed child appear unlikely given its limited excretion into breast milk of lactating women but cannot be fully excluded in the absence of infant safety data."

Journal • Endometriosis • Genito-urinary Cancer • Gynecology • Oncology • Prostate Cancer • Solid Tumor • Uterine Leiomyoma • Women's Health

▼Ryeqo for treatment of uterine fibroids. (PubMed, Drug Ther Bull) - No abstract available

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