Orilissa (elagolix) / Neurocrine, AbbVie - LARVOL DELTA

Role of Menopause in Thermoregulation (clinicaltrials.gov) - P4 | N=24 | Recruiting | Sponsor: Penn State University | Not yet recruiting ➔ Recruiting

Enrollment open

Significance of gut breast cancer resistance protein versus organic anion transporting polypeptide 2B1 inhibition on rosuvastatin clinical drug-drug interactions. (PubMed, Drug Metab Dispos) - "Organic anion transporting polypeptide (OATP)2B1 facilitates oral absorption of many drugs including celiprolol, fexofenadine, and rosuvastatin. Strong BCRP inhibition, with a G-value >100, translated to "positive" DDIs, whereas "OATP2B1-alone" inhibitors may lead to "negative" DDIs. For example, ronacaleret and elagolix significantly reduced rosuvastatin area under the curve due to strong OATP2B1 inhibition but weak BCRP inhibition."

Journal • Breast Cancer • Oncology • Solid Tumor • SLCO2B1

Brain Blood Flow Responses to Stress: Sex Differences (clinicaltrials.gov) - P4 | N=26 | Recruiting | Sponsor: University of Wisconsin, Madison | Trial primary completion date: Mar 2025 ➔ Jul 2025

Trial primary completion date • CNS Disorders • Vascular Neurology

An Oral GnRH Antagonist to Treat Mild Autonomous Cortisol Excess (MACE) Due to Adrenal Adenomas in Postmenopausal Women (clinicaltrials.gov) - P4 | N=4 | Terminated | Sponsor: Icahn School of Medicine at Mount Sinai | N=12 ➔ 4 | Recruiting ➔ Terminated; Difficulty recruiting patients

Enrollment change • Trial termination

Pre-IVF Treatment with a GnRH Antagonist in Women with Endometriosis_temp (clinicaltrials.gov) - P3 | N=288 | Recruiting | Sponsor: Yale University | Trial completion date: Jun 2026 ➔ Sep 2026

Trial completion date • Endometriosis • Gynecology • Infertility • Sexual Disorders • Women's Health

Comparison Elagolix vs Depot Leuprolide Prior to Frozen Embryo Transfers in Patients With Endometriosis (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Colorado Center for Reproductive Medicine | Active, not recruiting ➔ Completed

Trial completion • Endometriosis • Gynecology • Infertility • Sexual Disorders • Women's Health

A systematic review and meta-analysis comparing the use of elagolix therapy alone or in combination with add-back therapy to treat women with uterine fibroid associated heavy menstrual bleeding. (PubMed, Gland Surg) - "Compared with the elagolix treatment alone or with add-back therapy, the placebo was superior in terms of less bone mineral density change and a lower incidence of AEs. This study indicated that elagolix alone or in use with add-back therapy can be considered as a satisfactory treatment plan for the majority of patients who are diagnosed with uterine fibroids and HMB; however, the specific treatment plan should also consider patients' physical condition and any adverse reactions to the drug, based on existing research."

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

Role of Menopause in Thermoregulation (clinicaltrials.gov) - P4 | N=24 | Not yet recruiting | Sponsor: Penn State University

New P4 trial

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

Elagolix for ovulation suppression in in vitro fertilization: Is it time to switch from the painful costly injectables? (PubMed, F S Rep) - No abstract available

Journal • Preclinical • Gynecology • Pain

The role of elagolix in ovulation suppression during controlled ovarian stimulation: a retrospective cohort study. (PubMed, F S Rep) - "To compare in vitro fertilization treatment outcomes for the oral gonadotropin-releasing hormone (GnRH) antagonist elagolix (E) to the conventionally used injectable GnRH antagonist ganirelix (G) for achieving pituitary gonadotropin suppression during a controlled ovarian stimulation (COS) cycle. None of the differences reached significance. The oral GnRH antagonist, E, may be as effective as the injected antagonist, G, regarding embryological and clinical outcomes and could offer a less invasive, more cost-effective, and "patient-friendly" approach to pituitary suppression for in vitro fertilization treatment."

Journal • Retrospective data • Gynecology • Infertility • Sexual Disorders

Recent Advances in Individualized Clinical Strategies for Polycystic Ovary Syndrome: Evidence From Clinical Trials and Emerging Pharmacotherapies. (PubMed, Clin Ther) - "This comprehensive approach underscores the importance of tailored treatments in optimizing clinical outcomes and quality of life for women with PCOS. The aim of this review is to highlight recent advancements in the treatment of PCOS through clinical trials and emerging pharmacotherapies, emphasizing the need for individualized and multifaceted treatment approaches."

Journal • Review • Endocrine Disorders • Polycystic Ovary Syndrome

The use of oral GnRH antagonist to inhibit the LH surge in women undergoing ovarian stimulation for in vitro fertilization. (PubMed, Expert Rev Clin Pharmacol) - No abstract available

Journal • Preclinical • Gynecology

Cardiovascular Disease Risk in Women With Endometriosis (clinicaltrials.gov) - P1 | N=17 | Recruiting | Sponsor: Yale University | Trial completion date: Aug 2025 ➔ Dec 2026 | Trial primary completion date: Aug 2025 ➔ Dec 2025

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

Stability indicating RP-HPLC method development and validation for quantification of impurities in gonadotropin-releasing hormone (Elagolix): Robustness study by quality by design. (PubMed, Biomed Chromatogr) - "An accuracy range of LOQ to 150% was established for the method, and the average recovery was acceptable. Design of experiments, part of the quality by design idea, was used to prove the method's reliability."

Journal • Cerebral Hemorrhage

LONG-TERM ELAGOLIX + ADD-BACK THERAPY IN WOMEN WITH ENDOMETRIOSIS-ASSOCIATED PAIN FOR 48 MONTHS + 12 MONTH POST-TREATMENT FOLLOW-UP: A SAFETY UPDATE ON BONE MINERAL DENSITY DATA OF A PHASE 3 STUDY (ASRM 2024) - P3 | "OBJECTIVE To report the 12-month post-treatment follow-up (PTFU) of bone mineral density (BMD) data of a phase 3 study evaluating the long-term safety of elagolix 200 mg twice daily (ELA) with add-back therapy (AB; estradiol 1 mg/0.5 mg norethindrone acetate once daily) received in a 48-month treatment period in patients with endometriosis-associated pain (EAP; NCT03213457). a Recovery defined as (% CFB to final on-treatment visit − % CFB to PTFU visit) / (% CFB to final on-treatment visit) in patients who had a BMD decrease at their final on-treatment visit. Open table in a new tab"

Clinical • P3 data • Endometriosis • Gynecology • Osteoporosis • Pain • Women's Health

PROLONGED ORAL GnRH ANTAGONIST ADMINISTRATION PRIOR TO EUPLOID EMBRYO TRANSFER (ET) IN ENDOMETRIOSIS (ENDO) PATIENTS: A PROSPECTIVE RANDOMIZED NON-INFERIORITY TRIAL (ASRM 2024) - "Patients were randomized in a 1:1 ratio to receive either Elagolix (AbbVie, N. Chicago IL) 200 mg orally twice daily for 60 days (Group 1) or a depot preparation of leuprolide acetate (AbbVie) 3.75 mg intramuscularly every 28 days x 2 (Group 2) prior to medicated endometrial preparation for single blastocyst stage ET. We believe that this is the first time that this has been assessed. If results are confirmed in larger scale trials, this agent could be a more tolerable substitute for GnRHa in endo patients undergoing IVF."

Clinical • Head-to-Head • Endometriosis • Gynecology • Women's Health

DISPROPORTIONALITY ANALYSIS WITH COMPARISON OF ELAGOLIX VERSUS LEUPROLIDE SAFETY IN WOMEN WITH ENDOMETRIOSIS USING DATA FROM THE FDA ADVERSE EVENT REPORTING SYSTEM (FAERS) (ASRM 2024) - "AE signals are consistent with the known safety profile, except alopecia. SOC PT Drug N ROR 95% CI IC Lower limit Upper limit Gastrointestinal Nausea Egx 68 2.89 2.22 3.70 1.45 Lupron 41 1.02 0.75 1.40 0.65 Psychiatric Suicidal Ideation Egx 65 35.4 27.0 45.0 1.69 Lupron 14 3.98 2.34 6.76 1.97 Depression Egx 53 11.8 8.76 15.63 3.47 Lupron 29 2.99 2.07 4.34 1.54 Musculoskeletal and Connective tissue Arthralgia Egx 51 3.95 2.91 5.25 3.75 Lupron 45 2.81 2.08 3.80 1.44 Skin and subcutaneous tissue Alopecia Egx 32 3.56 2.29 5.30 2.16 Lupron 14 1.62 0.95 2.75 1.61 Open table in a new tab"

Adverse events • Clinical • Alopecia • CNS Disorders • Depression • Endometriosis • Gastrointestinal Disorder • Gynecology • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Pain • Psychiatry • Suicidal Ideation • Women's Health

GONADOTROPIN-RELEASING HORMONE ANTAGONISTS AS TREATMENT FOR AUTOIMMUNE PROGESTERONE DERMATITIS (ACAAI 2024) - "She was placed on norethisterone 5 mg daily with mild improvement however still experienced severe symptoms five days of the month, concerning for progestogen hypersensitivity. She started elagolix 200 mg twice daily, a GnRH antagonist, with resolution of her symptoms...This patient failed progesterone-only therapy, and to avoid the surge in sex hormones associated with GnRH agonists, was treated with a GnRH antagonist, which directly inhibits LH and FSH synthesis and release. This resulted in a more rapid reduction in progesterone levels without the initial surge associated with GnRH agonists."

Dermatitis • Dermatology • Endometriosis • Gynecology • Immunology • Musculoskeletal Pain • Pain • Rare Diseases • Women's Health

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 | Recruiting | Sponsor: AbbVie | Trial primary completion date: Dec 2024 ➔ Mar 2029

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

Impact of demographic and clinical factors on elagolix plus add-back therapy effects on patient-reported nonbleeding symptoms in women with heavy menstrual bleeding and uterine fibroids: a post hoc analysis of data from two clinical trials. (PubMed, F S Rep) - P3 | "To investigate the efficacy of elagolix plus add-back therapy (estradiol [1 mg] and norethindrone acetate [0.5 mg] once daily) on patient-reported nonbleeding symptoms and menstrual bleeding associated with uterine fibroids (UFs) across different subpopulations. Premenopausal women with heavy menstrual bleeding and UFs receiving elagolix plus add-back therapy experienced significant improvements in nonbleeding as well as bleeding symptoms from months 1-6, regardless of baseline characteristics. NCT02654054 and NCT02691494."

Journal • Retrospective data • Back Pain • Gynecology • Musculoskeletal Pain • Obstetrics • Pain • Solid Tumor • Uterine Leiomyoma • Women's Health

Novel non-peptide uracil-derived human gonadotropin-releasing hormone receptor antagonists. (PubMed, Eur J Med Chem) - "Docking and Molecular Dynamics (MD) studies revealed that 1 and 2 bind to GnRH1R with ΔG values comparable to elagolix, but through distinct binding modes. These results highlight the potential of non-peptide modulators to effectively modulate GnRH1R activity and pave the way for developing novel modulators."

Journal

Unraveling the complexity of amorphous solid as direct ingredient for conventional oral solid dosage form: The story of Elagolix Sodium. (PubMed, Int J Pharm) - "In addition, we applied material science tetrahedron concepts to link API porosity to drug product tablet compressibility. Finally, we designed the API isolation process, incorporating computational fluid dynamics modeling in the design of an impinging jet mixer for precipitation and solvent-dependent glass transition relationships in the cake wash, blow-down and drying process, to enable the consistent manufacture of a porous, non-sintered amorphous API powder that is suitable for robust drug product manufacturing."

Journal

The short- and mid-term efficacy and safety of elagolix in the management of pain associated with endometriosis: A systematic review and meta-analysis. (PubMed, J Gynecol Obstet Hum Reprod) - "The efficacy of elagolix in reducing pain in premenopausal women with endometriosis has been demonstrated over the short- to mid-term. However, careful monitoring for potential adverse effects is essential throughout the treatment duration."

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

Development and Application of a Physiologically Based Pharmacokinetic Model for Elagolix in the Adult and Adolescent Population. (PubMed, Clin Pharmacokinet) - "Our study presents a novel PBPK model for elagolix in healthy Chinese women, addressing a clinical data gap for its use in adolescents and obese patients. By validating the model with real-world factors, including diet and renal impairment, we provide initial pharmacokinetic predictions for these populations, contributing to a more informed clinical approach."

Journal • PK/PD data • Endometriosis • Genetic Disorders • Gynecology • Obesity • Pain • Renal Disease • Women's Health