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

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

Minimising Ureteric Injuries during Laparoscopic Hysterectomy for Broad ligament fibroids (ESGE 2024) - "Several treatments including Ryeqo and Prostap injections were intolerable due to side effects...Estimated blood loss was less than 500mls and no ureteric injuries were noted.Conclusions Pseudo broad ligament fibroids can be safely managed with laparoscopic hysterectomy and care should be taken to avoid ureteric injuries. Indocyanine green dye for highlighting ureteric paths has been found useful and can be considered if available."

Gynecology • Pain • Solid Tumor • Uterine Leiomyoma

effectiveness of relugolix combination therapy in a clinical setting: preliminary results of an italian multicenter real life experience. (ESGE 2024) - "Background to evaluate the effectiveness, tolerability and surgical advantages of the recently released GnRH-antagonist combination therapy (Relugolix-CT) containing estradiol 1mg and norethindrone acetate 0.5mg.Methods we performed a retrospective observational study at University Hospital Federico II (Naples) and at Public Hospital (Palermo) from Jun 1, 2022, to Jan 31, 2024. Further studies are needed to evaluate the possible use of this therapy in a fertility planning strategy, thus postponing surgery until desire for pregnancy rises. Moreover, our data show beneficial effects of the preoperatory treatment with Relugolix-CT for a successful and one-step myomectomy."

Clinical • Combination therapy • Pain • Uterine Leiomyoma • Women's Health

Experience of RYEQO treatment for Endometriosis, Adenomyosis and Uterine Fibroids - An observational study at Cwm Taf Morgannwg University Health Board, Wales (ESGE 2024) - "It contains 40mg Relugolix, 1mg Estradiol and 0.5mg Norethisterone acetate.It is indicated for treatment of moderate to severe symptoms of Uterine Fibroids and symptomatic treatment of endometriosis in women with history of previous medical or surgical treatment for endometriosis. Our study confirms that there is overall good symptom improvement in both fibroids and endometriosis and it can be used as one of the treatment options after the primary ones have failed. The sample size in our study is small, we continue to recruit patients and we will follow them to assess the long-term effects."

Clinical • Observational data • Acne Vulgaris • Alopecia • Endometriosis • Gynecology • Musculoskeletal Pain • Pain • Solid Tumor • Uterine Leiomyoma • Women's Health

Abnormal Uterine Bleeding With Leiomyomas: A Case Report of Its Natural Course and Therapeutic Management. (PubMed, Cureus) - "A supracervical hysterectomy, bilateral salpingectomy, lysis of adhesions, and left ovarian cystectomy were performed, resulting in symptom relief and benign postoperative findings. This case report highlights the need for personalized treatment plans and comprehensive patient counseling to manage complex gynecological conditions effectively."

Journal • Cardiovascular • Diabetes • Gynecology • Hypertension • Metabolic Disorders • Musculoskeletal Pain • Nephrology • Oncology • Pain • Renal Calculi • 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 | Not yet recruiting ➔ Recruiting

Enrollment open • Surgery • Endometriosis • Gynecology • Women's Health

The Effect of Medical Management Following Excisional Surgery for Endometriosis: A Randomized Controlled Trial (clinicaltrials.gov) - P3 | N=110 | Not yet recruiting | Sponsor: Main Line Health | Trial completion date: Apr 2027 ➔ Aug 2026

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

Surgical myomectomy followed by oral Myfembree vs standard of care (SOUL trial): Study protocol for a randomized control trial. (PubMed, PLoS One) - P4 | "In this project, we propose the use of daily dosed Relugolix combination therapy (Relugolix with estradiol and norethindrone acetate), which is approved for uterine fibroids treatment, has the potential to delay the recurrence of fibroid symptoms, prolong the improved quality of life and delay need for re-intervention after uterine sparing surgery."

Clinical • Clinical protocol • Journal • Gynecology • Obstetrics • Oncology • Solid Tumor • Uterine Leiomyoma • Women's Health

Adequacy of Estradiol/Norethindrone Acetate to Mitigate Dose-Dependent and Progressive Decline in Bone Mineral Density Observed with Gonadotropin-Releasing Hormone Receptor Agonism/Antagonism (ACOG 2024) - P2, P3 | "Introduction: Bone mineral density (BMD) data from the relugolix monotherapy endometriosis program were used to investigate the impact of relugolix combination therapy (Relugolix-CT: relugolix 40mg, estradiol 1mg, norethindrone acetate 0.5mg) on bone loss. Progressive and dose-dependent declines in BMD were observed with relugolix monotherapy; changes were comparable at Week 12 and 24 between relugolix 40mg (–2.10% and –4.90%, respectively) and leuprorelin (–2.21% and –4.43%). In women treated with relugolix monotherapy for 12 weeks who transitioned to Relugolix-CT, there was a decline in BMD at Week 12 (–1.72%), followed by stabilization at Week 24 (–1.86%), with upward drift for the remainder of treatment (Week 104: –0.56%). Women treated continuously with Relugolix-CT demonstrated a BMD decrease of less than 1% from baseline at Week 24 (–0.92%), followed by stabilization by Week 36 (–0.66%) and plateau through Week 104 (–0.45%)."

Endometriosis • Gynecology • Osteoporosis • Women's Health

Impact of Relugolix Combination Therapy on Functioning and Quality of Life in Women with Endometriosis-Associated Pain. (PubMed, Fertil Steril) - "Sustained reduction of endometriosis-associated pain with relugolix CT observed up to 104 weeks was accompanied by improvements in functioning and health-related QoL. These findings complement the results of the pivotal SPIRIT trials, which showed relugolix combination therapy significantly reduced dysmenorrhea, non-menstrual pelvic pain (NMPP) and dyspareunia vs placebo in premenopausal women with endometriosis-associated pain."

Combination therapy • HEOR • Journal • Endometriosis • Gynecology • Musculoskeletal Pain • Pain • Women's Health

Cumulative Benefit/Risk Profile of Relugolix Combination Therapy Through 104 Weeks for the Treatment of Endometriosis-Associated Pain (ACOG 2024) - "Introduction: Data from the SPIRIT long-term extension (LTE) demonstrated durability of treatment effect and tolerability for up to 104 weeks with once-daily relugolix combination therapy (Relugolix-CT: relugolix 40mg, estradiol 1mg and norethindrone acetate 0.5mg) for endometriosis-associated pain. Among 799 women, minimal-to-no dysmenorrhea was observed as early as 8 weeks in 56.3% of women, which increased to 94.5% at Week 52 and was sustained through 104 weeks (95.3%). Time to first BMD loss greater than 3% was observed in 13.1% of women at Week 24, 15.5% at Week 52, and 21.5% at Week 104. Z-scores remained within range for age."

Combination therapy • Endometriosis • Gynecology • Pain • Women's Health

The Effect of Medical Management Following Excisional Surgery for Endometriosis: A Randomized Controlled Trial (clinicaltrials.gov) - P3 | N=110 | Not yet recruiting | Sponsor: Main Line Health

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

Relugolix+estradiol+norethisterone for symptomatic uterine fibroids. (PubMed, Aust Prescr) - No abstract available

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

Effectiveness of Relugolix combination therapy in a clinical setting: preliminary results of an Italian multicenter real life experience. (ISGE 2024) - "Objective : to evaluate the effectiveness, tolerability and surgical advantages of the recently released GnRH-antagonist combination therapy (Relugolix-CT) containing estradiol 1mg and norethindrone acetate 0.5mg. A total of 73 women prescribed with Relugolix-CT were included. The mean age was 43.94 years (± 5.93) ranging from 25 to 52 years of age, 9.6% of patients had previously been treated with GnRH-agonists and 34.2% of women had myomectomies in the past. All patients reported HMB with a mean PBAC score of 328.79 (± 225.74)."

Clinical • Combination therapy • Pain • Uterine Leiomyoma • Women's Health

Sun Pharmaceutical Industries Gets CDSCO Panel Nod To Study FDC Of Relugolix, Estradiol, Norethindrone Acetate (Medical Dialogues) - "Rejecting for clinical trial waiver, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) opined the pharmaceutical major Sun Pharmaceutical Industries to conduct of Phase III clinical trial of the fixed-dose combination (FDC) of Relugolix, Estradiol and Norethindrone Acetate Tablets (40 mg + 1 mg + 0.5 mg) Tablets....The committee did not agree to the clinical trial waiver and the firm was asked to present Phase III СТ protocol in continuation with an earlier SEC recommendation dated 19th December 2023....At the recent SEC meeting for the Reproductive held on 20th March 2024, the expert panel reviewed the proposal presented by the drug major Sun Pharmaceutical Industries regarding the FDC Relugolix, Estradiol, and Norethindrone Acetate Tablets. After detailed deliberation, the committee recommended the conducting of a Phase III clinical trial as per the protocol presented by the firm."

New P3 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Relugolix/Estradiol/Norethisterone Acetate: A Review in Endometriosis-Associated Pain. (PubMed, Drugs) - "Relugolix combination therapy was generally well tolerated and BMD loss over time was minimal. With the convenience of a once daily oral dosing regimen, relugolix combination therapy is a valuable addition to the options currently available for the management of endometriosis-associated pain."

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

Quality of life improvements in women with uterine fibroids treated with relugolix combination therapy during the LIBERTY long-term extension study: A descriptive subgroup analysis in women with anemia at baseline. (PubMed, Int J Gynaecol Obstet) - "In women with UF and a high disease burden due to anemia, relugolix combination therapy substantially improved hemoglobin levels, decreased distress due to symptoms, especially fatigue, over 52 weeks."

Combination therapy • HEOR • Journal • Anemia • Fatigue • Gynecology • Hematological Disorders • Solid Tumor • Uterine Leiomyoma • 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=1020 | Active, not recruiting | Sponsor: Myovant Sciences GmbH | Trial completion date: Apr 2025 ➔ Feb 2026 | Trial primary completion date: Apr 2024 ➔ Feb 2025

Combination therapy • Trial completion date • Trial primary completion date • 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=60 | Not yet recruiting | Sponsor: NorthShore University HealthSystem

New P2 trial • Gynecology • Musculoskeletal Pain • Pain

TGA approves new medication for treatment of endometriosis symptoms (Guardian) - "Australian drug regulator gives company green light for tablet – although it won’t be subsidised by Pharmaceutical Benefits Scheme....On Friday the pharmaceutical company Gedeon Richter Australia announced that Ryeqo, a once-daily tablet, had been approved by the Therapeutic Goods Administration for the treatment of symptoms associated with endometriosis....But the drug will not be subsidised by the Pharmaceutical Benefits Scheme, which means a prescription will cost patients $135 or more for a one-month supply. Eligible patients will need a prescription from their specialist and the drug can be prescribed for up to two years."

Non-US regulatory • Pricing • Reimbursement • Endometriosis • Women's Health