Oriahnn (elagolix/estradiol/norethindrone acetate) / AbbVie, Neurocrine - 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

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

A Study to Evaluate Changes in Hair in Adult Participants Taking Oral Oriahnn Capsules With Heavy Menstrual Bleeding (HMB) Associated With Uterine Fibroids (UF) (clinicaltrials.gov) - P=N/A | N=1600 | Enrolling by invitation | Sponsor: AbbVie | Recruiting ➔ Enrolling by invitation

Enrollment status • Gynecology • Solid Tumor • Uterine Leiomyoma • 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 | 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

A Study to Evaluate Changes in Hair in Adult Participants Taking Oral Oriahnn Capsules With Heavy Menstrual Bleeding (HMB) Associated With Uterine Fibroids (UF) (clinicaltrials.gov) - P=N/A | N=1600 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Enrollment open • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

A Study to Evaluate Changes in Hair in Adult Participants Taking Oral Oriahnn Capsules With Heavy Menstrual Bleeding (HMB) Associated With Uterine Fibroids (UF) (clinicaltrials.gov) - P=N/A | N=1600 | Not yet recruiting | Sponsor: AbbVie

New trial • Gynecology • Solid Tumor • Uterine Leiomyoma • 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

Elagolix Improves Low Hemoglobin in Women With Uterine Fibroid-Associated Heavy Menstrual Bleeding: Post Hoc Analysis of Elaris UF-1 and UF-2 (ACOG 2023) - P3 | "We report improvement in hemoglobin (Hgb) levels over time with elagolix (ELA) with estradiol 1 mg/norethindrone acetate 0.5 mg once-daily add-back (AB) therapy in women with UF-associated HMB. ELA+AB results in rapid, sustained improvement in Hgb levels in women with UF-HMB, regardless of starting Hgb levels."

Clinical • Retrospective data • Anemia • Gynecology • Hematological Disorders • Solid Tumor • Uterine Leiomyoma • Women's Health

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

INTERIM RESULTS OF A PHASE 3b, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL EVALUATING 24-MONTH SAFETY OF ELAGOLIX WITH ADD-BACK FOR HEAVY MENSTRUAL BLEEDING ASSOCIATED WITH UTERINE FIBROIDS (ASRM 2022) - P3b | "MATERIALS AND This is a multicenter, phase 3b, sequential, randomized, 12‑month (M) double-blind, placebo-controlled, 36M open-label study to evaluate the safety of ELA 300 mg twice a day (BID) with estradiol 1 mg/norethindrone acetate 0.5 mg (E2/NETA) one a day AB (NCT03271489) in women with HMB associated with UF. The overall safety profile of ELA 300 mg BID with E2/NETA is consistent with its profile established from the previous Elagolix Uterine Fibroid Phase 3 studies in terms of overall AE rates and most frequent AEs. Safety findings at 24M were similar and consistent to those observed at the end of 12M with no new safety signals identified. IMPACT STATEMENT: The safety results from this study represent the longest duration of exposure to a GnRH agonist with E2/NETA add-back."

Clinical • P3 data • P3 data: top line • Back Pain • Cardiovascular • Gynecology • Hypertension • Infectious Disease • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Solid Tumor • Uterine Leiomyoma • Women's Health

IMPACT OF ELAGOLIX WITH ADD-BACK ON BONE MINERAL DENSITY AT 24 MONTHS: INTERIM RESULTS OF A RANDOMIZED, PLACEBO-CONTROLLED TRIAL IN WOMEN WITH HEAVY MENSTRUAL BLEEDING ASSOCIATED WITH UTERINE FIBROIDS (ASRM 2022) - P3b | "MATERIALS AND This is a multi-center, phase 3b, sequential, randomized, 12-month (M), double-blind, placebo-controlled, and 36M open-label trial to evaluate the effect of ELA 300 mg twice a day (BID) with estradiol 1 mg/norethindrone acetate 0.5 mg everyday AB (ELA+AB) on the BMD of women with HMB associated with UF (NCT03271489). Overall, the %CFB in BMD for patients completing 24M of ELA+AB treatment was approximately -1% for all 3 anatomic sites (lumbar spine, total hip, and femoral neck). These findings support the use of ELA 300 mg BID with E2/NETA in women with uterine fibroids and HMB over a 24M duration. IMPACT STATEMENT: In women experiencing HMB associated with UF, ELA+AB daily was associated with a relatively constant BMD change over a 24M treatment period."

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

"There should be pregnancy warning symbols on Oriahnn Elagolix, Fibristal/#Esmya, some NSAIDs & Statins, SSRIs, #Ryeqo #Relugolix Relumina Myfembree Orlissa, antidepressants, anticoagulants used by women/girls in childbearing years @MHRAgovuk @EMA_News @US_FDA #Exposome @NICEComms" (@FibroidNetwork)

NICE

Efficacy and safety of elagolix with add-back therapy in women with uterine fibroids and coexisting adenomyosis. (PubMed, F S Rep) - P3 | "Participants were randomized 1:1:2 to placebo, elagolix 300 mg twice daily alone, or elagolix 300 mg twice daily with estradiol 1 mg/norethindrone acetate 0.5 mg once daily. Adverse events most frequently reported in the elagolix with add-back adenomyosis subset were hot flushes (18.3%), nausea (11.7%), and night sweats (8.3%). Elagolix with add-back therapy significantly reduced heavy menstrual bleeding in women with uterine fibroids and coexisting adenomyosis, suggesting that elagolix efficacy was not adversely affected by the presence of adenomyosis (Elaris UF-1 and UF-2 Clinical-Trials.gov numbers, NCT02654054 and NCT02691494)."

Clinical • Journal • Endometriosis • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health • MRI

REACH: A Study to Assess Patient-Reported Quality of Life and Effectiveness on Control of Bleeding in Adult Participants With Heavy Menstrual Bleeding Due to Uterine Fibroids Taking Oral Oriahnn Capsules (clinicaltrials.gov) - P=N/A | N=23 | Terminated | Sponsor: AbbVie | N=200 ➔ 23 | Recruiting ➔ Terminated; Strategic considerations

Enrollment change • HEOR • Real-world evidence • Trial termination • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

"There should be pregnancy warning symbols on Oriahnn Elagolix, Fibristal/#Esmya, some NSAIDs & Statins, SSRIs, #Ryeqo #Relugolix Relumina Myfembree Orlissa, antidepressants, anticoagulants used by women/girls in childbearing years @MHRAgovuk @EMA_News @US_FDA #Exposome @NICEComms" (@FibroidNetwork)

NICE

Interdisciplinary Model-Informed Drug Development for Extending Duration of Elagolix Treatment in Patients with Uterine Fibroids. (PubMed, Br J Clin Pharmacol) - "The elagolix integrated exposure-BMD analysis and translation to fracture risk provided an interdisciplinary model-informed drug development framework for clinical benefit-risk evaluation and enabled approval of longer treatment duration to benefit the patient."

Journal • Gynecology • Musculoskeletal Diseases • Orthopedics • Solid Tumor • Uterine Leiomyoma

Baseline Characteristics of Patients Prior to Oriahnn Prescription (ISPOR 2022) - "Most patients using Oriahnn were greater than 39 year old, Caucasian, and have lower annual income. 43% did not have a claim for UF and/or HMB in the 6 months prior to starting Oriahnn. This suggests that diagnosed UF and HMB are not regularly recoded in claims databases."

Clinical • Anemia • Gynecology • Hematological Disorders • Solid Tumor • Uterine Leiomyoma

Long-Term Safety of Elagolix With Hormonal Add-Back Therapy in Women With Endometriosis-Associated Pain: 24-Month Results (ACOG 2022) - "Hormonal add-back therapy (1 mg estradiol/0.5 mg norethindrone acetate QD) may alleviate the hypoestrogenic effects (including bone mineral density [BMD] loss) associated with elagolix. Elagolix 200 mg BID+add-back therapy for 24M continues to have a favorable safety profile with minimal long-term impact on BMD. Combined with previously reported improvements in dysmenorrhea and non-menstrual pelvic pain, these safety data suggest elagolix 200 mg BID+add-back may provide a longer-term therapeutic option for women with EAP."

Clinical • Endometriosis • Gynecology • Musculoskeletal Pain • Pain