Orilissa (elagolix) / Neurocrine Biosciences, AbbVie - LARVOL DELTA

Current Evidence and Emerging Directions in Endometriosis Pharmacotherapy: A Systematic Review of Recent Advances. (PubMed, J Clin Med) - "This systematic review (2019-2025) synthesizes research results regarding the efficacy and safety of dienogest (DNG) and GnRH antagonists, while also summarizing research on new directions in endometriosis treatment...Relugolix combination therapy appears to be a more effective and safer option than elagolix or relugolix monotherapy in reducing dysmenorrhea and pelvic pain. Research concerning immunotherapy for endometriosis (using tocilizumab, anakinra, bevacizumab, and anti-CD47 antibodies) is subject to a high risk of bias and very low GRADE certainty...Research on GnRH antagonists indicates their increasing role in the future management of endometriosis. There are new perspectives in endometriosis pharmacotherapy-including immunotherapy; however, there is a fundamental need for their further development and evaluation."

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

Experimental and theoretical investigation of a 5-iodo-6-methyluracil derivative as a key intermediate for Elagolix synthesis: crystal structure, Hirshfeld surface analysis and DFT calculations. (PubMed, Acta Crystallogr C Struct Chem) - "Furthermore, frontier molecular orbital (FMO) analysis demonstrates a distinct spatial separation of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), establishing a typical donor-acceptor architecture that highly facilitates intramolecular charge transfer. The combined experimental and theoretical results provide a detailed characterization of the molecular geometry, noncovalent interactions and electronic structure of this key Elagolix intermediate, which may serve as a useful reference for understanding its solid-state behaviour."

Journal

Role of oral gonadotropin-releasing hormone antagonists in the management of uterine adenomyosis: a narrative review. (PubMed, Reprod Fertil) - "The objective of this narrative review was to investigate the efficacy of oral gonadotropin-releasing hormone (GnRH) antagonists in the management of uterine adenomyosis by analyzing data from two post hoc analyses of two prospective randomized trials (elagolix and relugolix), one retrospective study (relugolix) and one prospective study (linzagolix). Oral gonadotropin-releasing hormone (GnRH) antagonists have recently emerged as a promising new therapeutic option. Their advantages over GnRH agonist depot formulations include an absence of the flare-up effect, hence avoiding initially worsening symptoms and rapid reversibility."

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

Effect of Elagolix in Symptomatic Endometrioma in Comparison to Combined Oral Contraceptive Pill. (clinicaltrials.gov) - P=N/A | N=60 | Completed | Sponsor: Mst.Sumyara Khatun

New trial • Endometriosis

GnRH Analogues for the Treatment of Endometriosis-Related Pain: A Narrative Review. (PubMed, J Clin Med) - "Oral GnRH antagonists may offer practical advantages in selected patients through rapid action, the absence of a flare effect, and dose-adjustable hormonal suppression, although treatment choice must also consider long-term safety, cost, access, and individual patient characteristics. In summary, GnRH analogues remain useful second-line options, but treatment should be individualized according to symptom severity, previous treatment response, reproductive goals, tolerability, bone health, cost, and availability."

Journal • Review • Endometriosis • Gynecology • Infertility • Musculoskeletal Pain • Pain • Sexual Disorders • Women's Health

GnRH antagonists for the treatment of fibroids and adenomyosis, current evidence and future perspectives. (PubMed, Expert Opin Pharmacother) - "This narrative, based on a targeted PubMed/MEDLINE literature search and review of major guideline documents published up to May 2026, summarizes the pharmacological properties, mechanisms of action, and clinical evidence regarding GnRH antagonists (elagolix, relugolix and linzagolix) in uterine fibroids and adenomyosis. These agents should currently be considered suppressive rather than curative therapies, as symptoms often recur after discontinuation. Long-term integration into individualized treatment strategies will require further safety and comparative effectiveness data."

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

Role of Menopause in Thermoregulation (clinicaltrials.gov) - P4 | N=24 | Recruiting | Sponsor: Penn State University | Trial primary completion date: Jun 2026 ➔ Sep 2026

Trial primary completion date

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

ELARIS EM-COC: Study Of Oral Elagolix Tablets In Combination With Combined Oral Contraceptive Capsules/Tablets To Assess Dysmenorrhea Response In Adult Female Participants With Endometriosis And Associated Moderate To Severe Pain (clinicaltrials.gov) - P3 | N=800 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: Jun 2030 ➔ Jul 2027 | Trial primary completion date: Mar 2029 ➔ Jul 2027

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

An Oral GnRH Antagonist to Treat Mild Autonomous Cortisol Secretion Due to Adrenal Adenomas in Postmenopausal Women (ENDO 2026) - " We included postmenopausal women with benign appearing adenomas on CT scan, absence of clinical features of Cushing's Syndrome, abnormal 1mg dexamethasone suppression test (DST) with elevations in either late night salivary cortisol (LNSC) or 24-hour urine free cortisol (UFC). Elagolix may be an effective treatment for MACS in postmenopausal adenomas. IHC confirmed the presence of LH/hCG-R in resected adenomas (2/4 participants) that serve as a target for this therapy. Interestingly, in one participant with evidence of both MACS and primary aldosteronism, IHC staining showed no expression of CYP11B2 in the adenoma but did reveal LH/hCG-R expression in adjacent APMs."

Clinical • CNS Disorders • Cushing’s Disease • Depression • Endocrine Disorders • CYB5A • CYP11B1

Pre-IVF Treatment With a GnRH Antagonist in Women With endometriosis_temp (clinicaltrials.gov) - P3 | N=97 | Active, not recruiting | Sponsor: Yale University | Recruiting ➔ Active, not recruiting | N=297 ➔ 97 | Trial completion date: Sep 2026 ➔ Mar 2027 | Trial primary completion date: Jun 2026 ➔ Mar 2027

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Endometriosis • Gynecology • Infertility • Sexual Disorders • Women's Health

Antagonizing the corticotropin-releasing hormone receptor 1 with an orally bioavailable drug reduces endometriosis pain and associated adhesions†. (PubMed, Biol Reprod) - "Beginning 25 days after disease induction, rats received pexacerfont (10 mg/kg), vehicle, or elagolix (14 mg/kg) in 7-day treatment cycles separated by 7-day drug-free intervals up to day 60 after endometriosis onset...CRHR1 antagonism, therefore, suppressed neuro-inflammatory and proliferative pathways while limiting lesion-associated angiogenesis and postoperative adhesion development. These findings position CRHR1 as a mechanistically distinct, non-hormonal therapeutic target for endometriosis and highlight pexacerfont's potential to reduce both pain and adhesions."

Journal • Endometriosis • Gynecology • Inflammation • Pain • Women's Health • IL6 • LEP • TNFA

Efficacy and Safety of Elagolix Versus Dienogest for Treatment of Moderate-to-Severe Endometriosis Pain: A Phase III, Multicentric, Double-Blind, Active-Controlled, Non-Inferiority Study. (PubMed, BJOG) - "Elagolix demonstrated non-inferiority to dienogest with an acceptable safety and tolerability profile, supporting its use in managing endometriosis-associated pain."

Head-to-Head • Journal • P3 data • Endometriosis • Gynecology • Musculoskeletal Pain • Pain • 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

Catamenial Temporal Lobe Epilepsy Presenting with Ictal Asystole: A Case of Hormonal Modulation and Cardiac Pacing (AAN 2026) - "Initiation of elagolix, a gonadotropin-releasing hormone (GnRH) antagonist, eliminated both seizures and syncopal events. Seizure onset in the left frontotemporal region likely induced excessive vagal activation, compounded by progesterone withdrawal. Combined therapy with cardiac pacing and hormonal suppression successfully prevented both ictal systole and seizure clustering."

Clinical • Cardiovascular • CNS Disorders • Epilepsy

Expert opinion by Federation of Obstetric and Gynaecological Societies of India on elagolix - Redefining the endometriosis therapy landscape. (PubMed, Eur J Obstet Gynecol Reprod Biol) - "Elagolix provides dose-dependent oestrogen suppression and significant pain relief in all types of endometriosis pain, including dyspareunia. Elagolix also provides notable improvements in quality of life with a more favourable safety profile compared to conventional therapies. These attributes position elagolix as an emerging first-line treatment option for the management of endometriosis-associated pain."

Journal • CNS Disorders • Endometriosis • Fatigue • Gynecology • Musculoskeletal Pain • Obstetrics • Pain • Women's Health

New perspectives in managing chronic pelvic pain in Endometriosis: the role of GnRH antagonists versus dienogest. (PubMed, Expert Opin Pharmacother) - "We compare the pharmacological, pharmacokinetic, and safety profiles of dienogest and oral GnRH antagonists (elagolix, relugolix, linzagolix). Dienogest remains a well-tolerated long-term option in estrogen-sensitive patients, whereas GnRH antagonists are better suited for severe or refractory cases requiring rapid control. Integrating molecular and clinical profiling will be crucial to optimize individualized therapy and long-term outcomes."

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

Role of Menopause in Thermoregulation (clinicaltrials.gov) - P4 | N=24 | Recruiting | Sponsor: Penn State University | Trial primary completion date: Mar 2026 ➔ Jun 2026

Trial primary completion date

Single-Dose Bioequivalence Study of Elagolix Tablets 200 mg (Test Product) and Elagolix Tablets 200 mg (Reference Product) in Healthy Non-Pregnant, Non-Lactating Premenopausal Female Subjects Under Fasting Conditions. (PubMed, Clin Pharmacol Drug Dev) - "Both formulations exhibited comparable safety profiles, with only five mild, resolvable adverse events reported. These findings confirm that the test formulation is bioequivalent to the reference standard, supporting its viability as a safe and effective therapeutic alternative."

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

Insights on Medical Therapy for Uterine Fibroids: A Review. (PubMed, Adv Ther) - "Oral GnRH antagonists, which include elagolix, relugolix, and linzagolix, signify a substantial progression, providing rapid and reversible suppression of ovarian hormone synthesis with dose-dependent effects and enhanced convenience. Innovative treatment modalities that target nonhormonal mechanisms, such as extracellular matrix remodeling, angiogenesis, and gene modulation, provide promising prospects for future uterus-sparing interventions. This narrative review evaluates the current and advancing landscape of medical therapies for uterine fibroids, presenting evidence-based perspectives to inform clinical decision-making within an increasingly personalized therapeutic context."

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

Comparison of Letrozole with Elagolix for the Management of Endometriosis-Associated Pain: A Quasi-Experimental Study. (PubMed, J Coll Physicians Surg Pak) - "Elagolix demonstrated greater efficacy than Letrozole in reducing endometriosis-related pain after three months of treatment. This efficacy was more evident for dysmenorrhoea among specific patient subgroups, including those with younger age, lower BMI, or regular menstrual periods."

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

Efficacy and tolerability of elagolix in adolescents and young adults with endometriosis: a small, single-center retrospective cohort study. (PubMed, J Pediatr Adolesc Gynecol) - "In this small cohort, elagolix was associated with modest symptom improvement but high discontinuation rates in AYA with endometriosis. Larger prospective studies are needed to define its role in the long-term management of adolescent endometriosis."

Journal • Retrospective data • Endometriosis • Gynecology • Long-acting Reversible Contraceptives • Musculoskeletal Pain • Pain • Pediatrics • Women's Health

Atypical gelation of Elagolix sodium in aqueous media: Mechanistic insights and Inhibition via coamorphization. (PubMed, Eur J Pharm Biopharm) - "Coamorphization of ELS with quercetin (QUE) not only completely inhibits gelation but also significantly reduces the hygroscopicity of ELS. Overall, this study provides fundamental insights into the mechanism of atypical small-molecule gelation while offering a practical strategy to overcome gelation challenges in the formulation and processing of ELS-based pharmaceuticals."

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

Safety of 48 months of elagolix with add-back therapy for endometriosis-associated pain. (PubMed, AJOG Glob Rep) - "The addition of hormonal add-back (AB) therapy (1-mg estradiol/0.5-mg norethindrone acetate once daily) may attenuate BMD loss. BMD remained mostly stable through 48 months of continuous treatment. This analysis represents the longest safety study of ELA+AB therapy to date and supports long-term treatment with ELA+AB therapy."

Journal • Endometriosis • Gynecology • Infectious Disease • Musculoskeletal Pain • Novel Coronavirus Disease • Otorhinolaryngology • Pain • Respiratory Diseases • Sinusitis • Women's Health

Identifying Bioactive Conformation of GnRH1 Based on Molecular Docking of NMR Conformers to GnRH1R and mAbs. (PubMed, Proteins) - "Based on: (a) residues of GnRH1R interacting with antagonist elagolix (as ligand-binding pocket), (b) intermolecular hydrogen bonds (for specificity of interaction), and (c) total intermolecular non-covalent interactions (for stability of interaction), one NMR conformation, having an asymmetric U-turn reverse coil structure with a beta strand comprised of residues Gly6 and Leu7, is identified as the bioactive conformation of GnRH1...Molecular docking of the identified bioactive NMR conformation of GnRH1 to homology models of scFv attributes in vivo neutralizing ability of F1D3C5 to structure-specific recognition of GnRH1. The bioactive conformation of GnRH1 identified here could guide co-crystallization studies, design of analogs and GnRH1 vaccination efforts."

Journal • B3GAT1