CombiPatch (estradiol/norethindrone acetate) / Hisamitsu, Novartis - LARVOL DELTA

Long-Term Safety Study of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women (clinicaltrials.gov) - P3 | N=478 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Gynecology • 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

Assessment of the Improvement in Cognitive Levels of Postmenopausal Depression Patients by Estrogen (clinicaltrials.gov) - P=N/A | N=40 | Recruiting | Sponsor: Xiao Wang

New trial • CNS Disorders • Depression • Mood Disorders • Psychiatry

Bioequivalence of Elagolix/Estradiol/Norethindrone Acetate Fixed-Dose Combination Product: Phase 1 Results in Healthy Pre- and Postmenopausal Women. (PubMed, Clin Pharmacol Drug Dev) - "No safety concerns were identified. These results enabled bridging the elagolix/E2/NETA FDC capsule."

Journal • P1 data • Endometriosis • Gynecology • Pain • Solid Tumor • Uterine Leiomyoma • Women's Health

Long-Term Safety Study of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women (clinicaltrials.gov) - P3 | N=500 | Active, not recruiting | Sponsor: AbbVie | Phase classification: P3b ➔ P3 | Trial primary completion date: Aug 2023 ➔ Jul 2024

Combination therapy • Phase classification • Trial primary completion date • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

Drugs for menopausal symptoms. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal

A Clinical Study to Evaluate the Safety and Efficacy of Elagolix in Participants With Moderate to Severe Endometriosis-Associated Pain (clinicaltrials.gov) - P3 | N=681 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Trial completion • Endometriosis • Gynecology • Pain • Women's Health

Long-Term Safety Study of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women (clinicaltrials.gov) - P3b | N=500 | Active, not recruiting | Sponsor: AbbVie | Trial primary completion date: Nov 2023 ➔ Aug 2023

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

SPIRIT EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Endometriosis-Associated Pain (clinicaltrials.gov) - P3 | N=802 | Completed | Sponsor: Myovant Sciences GmbH | Active, not recruiting ➔ Completed

Trial completion • Endometriosis • Gynecology • Pain • Women's Health

Elagolix With Add-Back Therapy Improves Hemoglobin Concentration in Women With Fibroid-Associated Heavy Menstrual Bleeding Across Subgroups: Post Hoc Analysis of Elaris UF-1 and UF-2 (ACOG 2023) - P3 | "Here, we report the effect of elagolix with estradiol/norethindrone acetate add-back therapy (ELA+AB) on hemoglobin (Hgb) concentration across subpopulations of patients at 6 months of treatment. ELA+AB was effective in improving Hgb concentration across subgroups of premenopausal women with uterine fibroids and anemia (Hgb <10.5 g/dL), regardless of baseline demographics or clinical characteristics, which may therefore alleviate symptoms and reduce complications of anemia."

Clinical • Retrospective data • Anemia • Gynecology • Hematological Disorders • Obstetrics • Solid Tumor • Uterine Leiomyoma

Elagolix Plus Add-Back Consistently Improves Uterine Fibroids-Associated Bleeding and Nonbleeding Symptoms Across Subpopulations (ACOG 2023) - P3 | "INTRODUCTION: Patients with heavy menstrual bleeding (HMB) associated with uterine fibroids (UFs) have significantly improved menstrual blood loss (MBL) when taking elagolix+estradiol/norethindrone acetate add-back therapy (ELA+AB) versus placebo. ELA+AB provides better bleeding and nonbleeding symptom improvement versus placebo for patients with HMB associated with UFs, regardless of subpopulation investigated. In all populations, PGIC-MB and domain scores consistently reached or exceeded "much improved" by 6 months with ELA+AB."

Clinical • Back Pain • Gynecology • Musculoskeletal Pain • Obstetrics • Pain • Solid Tumor • Uterine Leiomyoma • Women's Health

Elagolix With Add-Back Rapidly Improves Nonbleeding Symptoms in Individuals With Fibroid-Associated Heavy Menstrual Bleeding (ACOG 2023) - P3 | "INTRODUCTION: Elagolix+estradiol/norethindrone acetate add-back therapy (ELA+AB) significantly improves heavy menstrual bleeding (HMB) in patients with uterine fibroids (UFs). ELA+AB provides rapid bleeding and nonbleeding symptom improvement for patients with UF-associated HMB. Improvement for ELA+AB–treated patients was observed as early as 1 month, with nonbleeding PGIC scores consistently approaching "much and very much improved" in all domains by 6 months."

Clinical • Back Pain • Gynecology • Musculoskeletal Pain • Pain • Solid Tumor • Uterine Leiomyoma

Virtual Bioequivalence Assessment of Elagolix Formulations Using Physiologically Based Pharmacokinetic Modeling. (PubMed, AAPS J) - "As a combination therapy, two individual tablets, consisting of an elagolix tablet and an estradiol/norethindrone acetate 1/0.5 mg (E2/NETA) tablet, were utilized in Phase 3 endometriosis trials. Based on results of the virtual bioequivalence simulations, the commercial drug product capsules met the bioequivalence criteria of 0.80-1.25 when compared to the reference tablets. This was a novel example where PBPK modeling was utilized along with in vitro dissolution data to demonstrate virtual bioequivalence in support of a regulatory bioequivalence waiver."

Journal • PK/PD data • Endometriosis • Gynecology • Women's Health

A Clinical Study to Evaluate the Safety and Efficacy of Elagolix in Participants With Moderate to Severe Endometriosis-Associated Pain (clinicaltrials.gov) - P3 | N=681 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: Jan 2023 ➔ Jan 2024

Combination therapy • Trial completion date • Endometriosis • Gynecology • Pain • Women's Health

Long-Term Safety Study of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women (clinicaltrials.gov) - P3b | N=500 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: Jan 2025 ➔ Jul 2024 | Trial primary completion date: Aug 2023 ➔ Nov 2023

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

Efficacy and Safety of Oral GnRH antagonists in Patients with Uterine Fibroids: A Systematic Review. (PubMed, J Obstet Gynaecol Can) - "Among oral GnRH antagonists, relugolix, elagolix, and linzagolix were safe in patients with uterine fibroids. These drugs, alone and in combination with estradiol/norethindrone acetate (E2/NETA), showed significantly better efficacy than placebo in improving bleeding, discomfort, uterine/leiomyoma sizes, and quality of life in premenopausal patients with symptomatic uterine fibroids. However, more randomized double blind multicenter clinical trials are needed to confirm these results and to see long-term benefits."

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

Efficacy and Safety of Elagolix 150 mg QD in Women With Uterine Fibroids and Heavy Menstrual Bleeding (ACOG 2022) - "INTRODUCTION: Elagolix is an oral GnRH antagonist approved in combination with hormonal add back therapy (elagolix 300 mg BID+estradiol/norethindrone acetate QD) for the treatment of heavy menstrual bleeding (HMB) associated with uterine fibroids (UF) for up to 24 months (M). Elagolix 150 mg QD alone significantly reduced HMB in patients with UF after 6M of treatment with no new safety signals and may be an effective therapeutic option for patients with contraindications to estradiol and/or norethindrone acetate."

Clinical • Gynecology • Pain • Solid Tumor • Uterine Leiomyoma

Study of Relugolix With Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids (clinicaltrials.gov) - P3 | N=229 | Completed | Sponsor: Myovant Sciences GmbH | Active, not recruiting ➔ Completed | Trial completion date: Mar 2022 ➔ Nov 2021

Trial completion • Trial completion date • Gynecology • Solid Tumor • Uterine Leiomyoma

Long-Term Safety Study of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women (clinicaltrials.gov) - P3b | N=500 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: Jul 2024 ➔ Jan 2025

Combination therapy • Trial completion date • Gynecology • Solid Tumor • Uterine Leiomyoma

An evaluation of relugolix/estradiol/norethindrone acetate for the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. (PubMed, Expert Opin Pharmacother) - "However, it should be used with hormonal add-back therapy (E2+ NETA) to avoid induced hypoestrogenic side effects, importantly bone mineral density loss. Moreover, symptoms will likely resume shortly after the termination of the relugolix combination administration."

Journal • Gynecology • Oncology • Solid Tumor • Uterine Leiomyoma

Elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid: a systematic review and meta-analysis. (PubMed, BMC Womens Health) - "Elagolix appeared to be effective in reducing heavy menstrual bleeding caused by uterine fibroid and combination with estradiol/norethindrone acetate was able to alleviate the hypoestrogenism side effects in premenopausal women. Review registration PROSPERO CDR 42021233898."

Clinical • Journal • Retrospective data • Review • Gynecology • Solid Tumor • Uterine Leiomyoma

Population Pharmacokinetics of Elagolix in Combination with Low-Dose Estradiol/Norethindrone Acetate in Women with Uterine Fibroids. (PubMed, Clin Pharmacokinet) - P3 | "Elagolix population pharmacokinetics modeling did not reveal any patient-related factors or clinical parameters that would require dose adjustments for the approved dosage of 300 mg twice daily with estradiol 1 mg /norethindrone acetate 0.5 mg daily, in women with heavy menstrual bleeding associated with uterine fibroids."

Clinical • Combination therapy • Journal • PK/PD data • Endometriosis • Gynecology • Pain • Solid Tumor • Uterine Leiomyoma

Current approaches to overcome the side effects of GnRH analogs in the treatment of patients with uterine fibroids. (PubMed, Expert Opin Drug Saf) - "We also focused on clinical studies exploring the therapeutic benefits of novel oral non-peptide GnRH antagonist that were recently approved by the US Food and Drug Administration (FDA) in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with UFs in premenopausal women. The results regarding the efficacy of new-generation oral GnRH-antagonists, such as elagolix, relugolix and linzagolix, is promising and offer potential prospect for the future therapy of UFs. However, these antagonists must be combined with hormonal Add-back therapy to minimize the resultant hypoestrogenic side effects such as bone loss."

Adverse events • Clinical • Journal • Gynecology • Oncology • Osteoporosis • Solid Tumor • Uterine Leiomyoma

Study of Relugolix With Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids (clinicaltrials.gov) - P3; N=229; Active, not recruiting; Sponsor: Myovant Sciences GmbH; Trial completion date: Aug 2021 ➔ Mar 2022

Clinical • Trial completion date • Gynecology • Solid Tumor • Uterine Leiomyoma

Elagolix in the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. (PubMed, Expert Rev Clin Pharmacol) - "Authors reviewed the literature available for elagolix; an orally bioavailable, second-generation, non-peptide gonadotropin-releasing hormone (GnRH) antagonist recently approved by the US Food and Drug Administration (FDA) in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with UFs in premenopausal women. The utility of new-generation oral GnRH-antagonists, such as elagolix, relugolix and linzagolix, is offering a new potential opportunity for the future therapy of UFs: elagolix has been the most studied drug of this class for treating benign gynecological diseases including endometriosis and UFs, for which it has been US FDA-approved in 2018 and 2020 respectively."

Clinical • Journal • Endometriosis • Gynecology • Oncology • Solid Tumor • Uterine Leiomyoma